technetium-tc-99m-exametazime and Alzheimer-Disease

Investigators have reported high sensitivity and specificity values for single photon emission computerized tomography (SPECT) when distinguishing Alzheimer's disease (AD) patients from normal elderly controls or from selected patient groups. The role of SPECT in identifying AD among unselected patients with memory complaints requires investigation. We examined 139 consecutive patients with 99Tc-HMPAO SPECT. NINCDS-ADRDA diagnoses were determined blind to SPECT results, and scans were read and classified by visual inspection blind to clinical diagnoses. Bilateral temporoparietal hypoperfusion (TP) occurred in 75% of probable, 65% of possible, and 45% of unlikely AD patients, yielding a sensitivity of 75% and a specificity of 52% when comparing probable AD versus unlikely AD groups. A positive predictive value of 78% was obtained based on a 69% prevalence of AD in our total clinic population. Patients with false-positive results included a variety of dementing illnesses; all patients with bilateral hypoperfusion had dementia. A pattern of TP on SPECT scans is seen in most patients with AD, but could be found in other dementias as well and cannot be regarded as specific to AD. Reduced TP perfusion discriminated between demented and nondemented individuals. Further strategies for SPECT interpretation that improve diagnostic specificity should be sought.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Dementia; Dementia, Vascular; Diagnosis, Differential; Dominance, Cerebral; Humans; Organotechnetium Compounds; Oximes; Parietal Lobe; Reference Values; Regional Blood Flow; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

Recent and future evolutions in neuroSPECT apply to radiopharmaceuticals techniques and the synergistic use of different imaging modalities in the work-up of neurological disorders. The introduction of Technetium labelled perfusion tracers, which could pass the intact blood-brain barrier, together with the implementation of the tomographic principle, by making the conventional gamma camera rotating, enabled estimation of regional cerebral blood flow and indirectly of local brain metabolism. In addition at present Thallium-201 and Tc-99m sestaMIBI allow functional detection of viable tumor tissue, without interference from previous surgery or radiotherapy as seen using CT-scan or MRI. In neurology this has led to the recognition of SPECT by the American Academy of Neurology (Therapeutics and technology subcommittee) as an established or promising tool in major neurological disorders such as dementia, stroke and epilepsy, while other domains such as brain oncology are considered investigational. With regard to radiopharmaceuticals, recent evolutions mainly include the development of mostly Iodine-123 labelled receptor ligands, some of which are already commercially available. For instrumentation advances consist e.g. of multidetector systems equipped with fanbeam collimators, attenuation and scatter correction or coincidence detection. Given the present role for nuclear neurology it may be expected that these additional radiopharmaceutical and technical innovations will continue to stimulate the development of SPECT of the brain. The synergistic use of several imaging techniques such as CT, (functional) MRI, source imaging, SPECT and PET represents a multimodal holistic approach to probe cerebral functions for research and clinical purposes. Clinical indications, in which this synergistic use is illustrated include e.g. support of the clinical diagnosis of dementia of the Alzheimer type, presurgical ictal detection of seizure focus, detection of acute ischemia and differential diagnosis between radiation necrosis and brain tumor recurrence. The synergistic use of imaging modalities, optimally applied using image fusion, allows to overcome the intrinsic limitations and to enhance the specific advantages of the different approaches as it leads to increased precision and accuracy, as well for spatial anatomofunctional correlation as for quantification.

Topics: Alzheimer Disease; Brain Ischemia; Brain Neoplasms; Epilepsy; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Mental Disorders; Nervous System Diseases; Neurology; Nitriles; Technetium Tc 99m Exametazime; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Brain imaging has become an integral part of the evaluation of neurological and psychiatric disorders. Functional imaging techniques, SPECT and PET, together with structural modalities, CT and MRI, are widely employed. Functional imaging studies are routinely used in the diagnostic workup of patients with well-characterized neurological disorders, such as epilepsy and brain tumors, and have a growing role in research on psychiatric disorders without known mechanisms such as depression and schizophrenia. Furthermore, many well-defined neurological disorders manifest prominent psychiatric symptomatology which may pose difficulties in differential diagnosis. This review addresses the current knowledge of SPECT findings in patients who present with psychiatric phenomena, associated with disorders at the interface of neurology and psychiatry.

Topics: Alzheimer Disease; Brain; Brain Damage, Chronic; Brain Diseases; Brain Injuries; Brain Neoplasms; Dementia; Diagnosis, Differential; Epilepsy, Temporal Lobe; Humans; Huntington Disease; Neurocognitive Disorders; Organotechnetium Compounds; Oximes; Parkinson Disease; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

This review critically evaluates the current role of single photon emission tomography (SPET) imaging in the clinical management of patients with dementia. The classification of the dementias is discussed and the clinical and pathological features of the various dementing illnesses are described. Typical appearances on cerebral blood flow imaging are presented for each of the conditions, together with the findings on D2 dopaminergic receptor and muscarinic receptor imaging where this is relevant. The review concludes with a section on the clinical value of SPET imaging in dementia. SPET imaging can make a valuable contribution to the accurate clinical differentiation of dementia, providing findings are interpreted in the light of neurological evaluation and structural imaging. The possible future role of SPET imaging in the prediction and evaluation of response to future therapeutic agents is discussed.

Topics: Alzheimer Disease; Brain; Brain Diseases; Dementia; Humans; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed

Functional imaging studies in patients with dementia have focused primarily on the reliability of scan patterns to correctly diagnose specific diseases, particularly Alzheimer's disease. Results from these studies have important implications as disease-specific treatments become available. A complementary approach is to examine the relationships between patterns of altered brain function and specific behaviors. This tactic has potential impact on understanding normal brain organization as well as targeting symptom-specific treatments. Regional abnormalities have been identified in dementia patients that correlate with specific behavioral deficits: disturbances of language and visuospatial function, impaired verbal fluency and selective attention, and the presence of delusions and depression. These patterns are seen in patients with Alzheimer's disease as well as with dementias of other etiologies. The specificity of these patterns for disease-specific and disease-independent symptoms is unknown.

Topics: Alzheimer Disease; Brain; Cognition Disorders; Delusions; Dementia; Deoxyglucose; Depressive Disorder; Diagnosis, Differential; Fluorodeoxyglucose F18; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Severity of Illness Index; Technetium Tc 99m Exametazime; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

The most common cause of dementia in the developed world is Alzheimer's disease. Histopathology is required to confirm diagnosis, but most evaluations of the accuracy of clinical criteria and neuroimaging in the diagnosis of dementia of the Alzheimer type are without such confirmation. The average specificity of clinical criteria alone is about 75%. This paper discusses the contribution of simple structural (x-ray computed tomography [CT]) and functional (Tc-99m-HMPAO single photon emission computed tomography [SPECT]) imaging to the diagnosis of Alzheimer's disease in 71 histopathologically confirmed cases (47 with Alzheimer's disease, 16 with other dementias, 8 controls) and 84 living controls. Medial temporal lobe atrophy assessed by temporal lobe-oriented CT gave 94% sensitivity and 93% specificity, while parietotemporal hypoperfusion on SPECT revealed 96% sensitivity and 89% specificity. The combination of both changes yielded a sensitivity of 90% and a specificity of 97%. These investigations clearly enhance diagnostic accuracy, can be readily applied in the clinical situation, and could be used in epidemiologic studies of Alzheimer's disease.

Topics: Alzheimer Disease; Dementia; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Organotechnetium Compounds; Oximes; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Topics: Alzheimer Disease; Brain; Cerebrovascular Circulation; Cognition Disorders; Deoxyglucose; Female; Fluorodeoxyglucose F18; Glucose; Humans; Male; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

To examine the utility of single-photon emission computed tomography (SPECT) to predict conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD).. Longitudinal, prospective study.. University-based memory disorders clinic.. One hundred twenty seven patients with MCI and 59 healthy comparison subjects followed up for 1-9 years.. Diagnostic evaluation, neuropsychological tests, social/cognitive function, olfactory identification, apolipoprotein E genotype, magnetic resonance imaging, and brain Tc hexamethyl-propylene-aminoxime SPECT scan with visual ratings, and region of interest (ROI) analyses were done.. Visual ratings of SPECT temporal and parietal blood flow did not distinguish eventual MCI converters to AD (N = 31) from nonconverters (N = 96), but the global rating predicted conversion (41.9% sensitivity and 82.3% specificity, Fisher's exact test p = 0.013). Blood flow in each ROI was not predictive, but when dichotomized at the median value of the patients with MCI, low flow increased the hazard of conversion to AD for parietal (hazard ratio: 2.96, 95% confidence interval: 1.16-7.53, p = 0.023) and medial temporal regions (hazard ratio: 3.12, 95% confidence interval: 1.14-8.56, p = 0.027). In the 3-year follow-up sample, low parietal (p <0.05) and medial temporal (p <0.01) flow predicted conversion to AD, with or without controlling for age, Mini-Mental State Examination, and apolipoprotein E ε4 genotype. These measures lost significance when other strong predictors were included in logistic regression analyses: verbal memory, social/cognitive functioning, olfactory identification deficits, hippocampal, and entorhinal cortex volumes.. SPECT visual ratings showed limited utility in predicting MCI conversion to AD. The modest predictive utility of quantified low parietal and medial temporal flow using SPECT may decrease when other stronger predictors are available.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Apolipoprotein E4; Atrophy; Brain; Cerebrovascular Circulation; Cognition Disorders; Disease Progression; Female; Genotype; Humans; Male; Middle Aged; Oximes; Predictive Value of Tests; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Current diagnosis of Alzheimer disease is made by clinical, neuropsychologic, and neuroimaging assessments. Neuroimaging techniques such as magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) could be valuable in the differential diagnosis of Alzheimer disease, as well as in assessing prognosis.. To compare SPECT and MRI in a cohort of patients examined for suspected dementia, including patients with no objective cognitive impairment (control group), mild cognitive impairment (MCI), and Alzheimer disease (AD).. 24 patients, eight with AD, 10 with MCI, and six controls, were investigated with SPECT using (99m)Tc-hexamethylpropyleneamine oxime (HMPAO, Ceretec; GE Healthcare Ltd., Little Chalsont UK) and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with a contrast-enhancing gadobutrol formula (Gadovist; Bayer Schering Pharma, Berlin, Germany). Voxel-based correlation between coregistered SPECT and DSC-MR images was calculated. Region-of-interest (ROI) analyses were then performed in 24 different brain areas using brain registration and analysis of SPECT studies (BRASS; Nuclear Diagnostics AB, Stockholm, Sweden) on both SPECT and DSC-MRI.. Voxel-based correlation between coregistered SPECT and DSC-MR showed a high correlation, with a mean correlation coefficient of 0.94. ROI analyses of 24 regions showed significant differences between the control group and AD patients in 10 regions using SPECT and five regions in DSC-MR.. SPECT remains superior to DSC-MRI in differentiating normal from pathological perfusion, and DSC-MRI could not replace SPECT in the diagnosis of patients with Alzheimer disease.

Topics: Aged; Alzheimer Disease; Brain; Brain Mapping; Cohort Studies; Contrast Media; Diagnosis, Differential; Echo-Planar Imaging; Female; Humans; Image Enhancement; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Male; Middle Aged; Organometallic Compounds; Predictive Value of Tests; Radiography; Reproducibility of Results; Severity of Illness Index; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Alzheimer's disease (AD) is a primary degenerative disease that progressively affects all brain functions, with devastating consequences for the patient, the patient's family and society. Rest regional cerebral blood flow (rCBF) could have a strategic role in differentiating between AD patients and normal controls, but its use for this purpose has a low discriminatory capacity. The purpose of this study was to evaluate whether the diagnostic sensitivity of rCBF single-photon emission computed tomography (SPECT) could be increased by using an episodic memory task provocation, i.e. memory-provoked rCBF-SPECT (MP-SPECT).. Eighteen persons (73.2+/-4.8 years) with mild AD and 18 healthy elderly (69.4+/-3.9 years) were included in the study. The subjects were injected with (99m)Tc-hexamethylpropylene amine oxime (HMPAO) during memory provocation with faces and names, followed by an rCBF-SPECT study. The rCBF (99m)Tc-HMPAO SPECT images were analysed using statistical parametric mapping (SPM2). Peaks with a false discovery rate corrected value of 0.05 were considered significant.. On MP-SPECT, the AD group showed a significant rCBF reduction in the left parietal cortex in comparison with healthy elderly. At rest, no significant group differences were seen.. Memory provocation increased the sensitivity of rCBF-SPECT for the detection of AD-related blood flow changes in the brain at the group level. Further studies are needed to evaluate MP-SPECT as a diagnostic tool at the individual level. If a higher sensitivity for AD at the individual level is verified in future studies, a single MP-SPECT study might be sufficient in the clinical setting.

Topics: Adult; Aged; Alzheimer Disease; Brain; Brain Mapping; Cerebrovascular Circulation; Evoked Potentials; Female; Humans; Image Interpretation, Computer-Assisted; Male; Memory; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

There is an increasing interest in the effects of the acetylcholinesterase inhibitors (AChEIs) in Alzheimer's disease (AD), as investigated by means of objective, neurophysiological tools. In an open-label study, we evaluated the neurophysiological effects of chronic administration of donepezil to AD patients, by means of a correlative approach between quantitative EEG (qEEG) and perfusional brain single photon emission computed tomography (SPECT).. Sixteen patients (mean age: 74.8+/-7.9 years) with mild to moderate AD (MMSE score >13, mean: 20.7+/-4.6) underwent qEEG and SPECT examinations at the time of diagnosis (t0) and after approximately 1 year of donepezil therapy (t1). The brain SPECT (99mTc-hexamethylpropyleneamine oxime) was performed by means of a high-resolution SPECT camera; the qEEG was recorded from 19 scalp electrodes by average reference and digitized at 512 Hz. The mean frequency (MF) value of the mean power spectrum (fast Fourier transform) from 4 brain regions (one frontal and one temporal-parietal in each hemisphere) was chosen for statistical analysis. Changes in MMSE score and qEEG-MF values between t0 and t1 were assessed by analysis of variance. SPECT differences between t0 and t1, as well as the relationships between SPECT and qEEG changes, were assessed by statistical parametric mapping (SPM 99; height threshold: P=0.001 at cluster level).. Between t0 and t1, the MMSE score significantly (P<0.05) decreased (from 20.7+/-4.64 to 19.1+/-5.09; 95% confidence interval: 1.14) and qEEG was unchanged. There was no regional perfusion decrease; a small area of relative perfusion increase was observed, including the right occipital cuneus and the left lingual gyrus. A positive correlation was found between the right frontal MF and brain perfusion in the left superior parietal lobule. A post hoc SPM analysis (height threshold: P=0.01) showed a positive correlation between brain perfusion and each of the 4 qEEG MF values in the left parietal lobe, including the precuneus, the superior parietal lobule, and the post-central gyrus.. The posterior parietal region, which is involved in memory and attention, is often affected by hypoperfusion in AD, as a likely consequence of disconnection from the atrophic mesial temporal cortex. Metabolic activation induced by AChEIs may especially influence this disconnected but still not grossly impaired area, which could be one of the pathophysiological substrates of the cognitive effects of AChEIs. The modest topographical sensitivity of qEEG, reflecting the rather diffuse changes in AD, is further confirmed.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cerebrovascular Circulation; Donepezil; Electroencephalography; Female; Humans; Indans; Male; Middle Aged; Nootropic Agents; Piperidines; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

This study was designed to quantify the heterogeneity on cerebral blood flow single-photon emission tomography (SPET) images in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) using a three-dimensional fractal analysis. Twenty-one FTLD patients, 21 AD patients and 11 healthy controls underwent technetium-99m hexamethylpropylene amine oxime SPET scanning. Patients with FTLD and AD matched for sex, age and the severity of dementia as estimated with the Clinical Dementia Rating and were determined to be in the early stage of illness. We delineated the SPET images using a 35% cut-off and a 50% cut-off of the maximal voxel radioactivity and measured the number of voxels included in the contours of two different cut-offs. The fractal dimension (FD) was calculated by relating the logarithms of the cut-offs and the numbers of voxels, and it was defined as the heterogeneity of the cerebral perfusion. We divided the SPET images into two sets, anterior and posterior, with equal numbers of coronal SPET slices. We calculated total FD, anterior FD and posterior FD for total, anterior and posterior SPET images. Anterior FDs for FTLD and AD were 1.55 +/- 0.34 and 1.24 +/- 0.19 (P = 0.0002). The ratios of anterior to posterior FD for FTLD and AD were 1.81 +/- 0.41 and 1.32 +/- 0.14 (P < 0.0001). Use of the anterior FD and the ratio of anterior to posterior FD separated FTLD patients from AD patients and controls with a sensitivity of 85.7% and a specificity of 93.8%. Anterior FD and the ratio of anterior to posterior FD may be useful in distinguishing FTLD from AD.

Topics: Aged; Alzheimer Disease; Blood Flow Velocity; Brain; Cerebrovascular Circulation; Dementia; Diagnosis, Differential; Female; Fractals; Humans; Imaging, Three-Dimensional; Male; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Hypoperfusion in the posterior cingulate cortex is thought to be useful for the early diagnosis of dementia of Alzheimer type (DAT). In the present study, we compared the incidence of posterior cingulate hypoperfusion in patients with Alzheimer's disease (AD), patients with senile dementia of Alzheimer type (SDAT), and patients with other types of dementia, as evaluated by three-dimensional stereotactic surface projection (3D-SSP) imaging. The subjects were 20 AD patients, 20 SDAT patients, 13 frontotemporal dementia patients, and 3 other types of dementia patients. A SPECT study was performed 5 minutes after the injection of 740 MBq technetium-99m hexamethylpropylene amine oxime. 3D-SSP images were obtained with global normalization to perform the statistical analysis. The normal database of 3D-SSP consisted of 15 healthy volunteers. Hypoperfusion was considered to be significant when the Z-score was over 2.5. Posterior cingulate hypoperfusion was observed in 13 of 20 AD patients (65%), in 5 of 20 SDAT patients (25%), but in none of other type of dementia patients. Posterior cingulate hypoperfusion was considered to be a finding specific to DAT, and this finding was thought to be useful to diagnose DAT patients, especially for AD patients. However, it was considered to be difficult to diagnose early-stage SDAT patients.

Topics: Aged; Alzheimer Disease; Brain Ischemia; Cerebrovascular Circulation; Dementia; Female; Gyrus Cinguli; Humans; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Male; Middle Aged; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index; Statistics as Topic; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

An acetylcholine deficit remains the most consistent neurotransmitter abnormality found in Alzheimer's disease and various therapeutic agents have been targeted at this. In this study we investigated the action of Donepezil, a cholinesterase inhibitor that has few side-effects. In particular we set out to investigate whether muscarinic acetylcholine receptor (mAChR) availability influences the response to this therapy. We used the novel single-photon emission tomography (SPET) tracer (R, R)[(123)I]I-quinuclidinyl benzilate (R, R[(123)I]I-QNB), which has high affinity for the M1 subtype of mAChR. Regional cerebral perfusion was also assessed using technetium-99m hexamethylpropylene amine oxime. We investigated 20 patients on Donepezil treatment and ten age-matched controls. The results showed a reduction in (R, R)[(123)I]I-QNB binding in the caudal anterior cingulate in patients compared with controls and relatively high binding in the putamen and rostral anterior cingulate, suggesting a relative sparing of mAChR in these regions. The main finding of the study was that mAChR availability as assessed by (R, R)[(123)I]I-QNB binding did not distinguish responders from non-responders. Interestingly, we found that the extent of cognitive improvement showed no positive correlation with (R, R)[(123)I]I-QNB binding in any brain region but was inversely related to binding in the insular cortex. This suggests that, within the advised cognitive performance band for use of Donepezil, response is greater in those patients with evidence of a more marked cholinergic deficit. A larger study should investigate this.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Cerebrovascular Circulation; Cholinesterase Inhibitors; Donepezil; Female; Humans; Indans; Male; Middle Aged; Piperidines; Psychiatric Status Rating Scales; Quinuclidinyl Benzilate; Radionuclide Imaging; Radiopharmaceuticals; Receptor, Muscarinic M1; Receptors, Muscarinic; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic; Technetium Tc 99m Exametazime; Tissue Distribution; Treatment Outcome

The goal of this study was to perform a systematic, semi-quantitative analysis of limbic perfusion in patients with Alzheimer's disease (AD) using coregistered single-photon emission tomography (SPET) images aligned to magnetic resonance (MR) images. Limbic perfusion in 40 patients with mild to moderate AD was compared with that of 17 age-, sex-, and education-matched normal controls (NC). HMPAO SPET scans and 3D T1-weighted MR images were acquired for each subject. Structures of the limbic system (i.e. hippocampus, amygdala, anterior thalamus, hypothalamus, mamillary bodies, basal forebrain, septal area and cingulate, orbitofrontal and parahippocampal cortices) were traced on the MR images and transferred to the coregistered SPET scans. Perfusion ratios for all limbic regions were calculated relative to cerebellar perfusion. General linear model multivariate analysis revealed that, overall, limbic structures showed significant hypoperfusion (F=7.802, P<0.00001, eta (2)=0.695 ) in AD patients compared with NC. Greatest differences (d > or = 0.8) were found in the hippocampus, as well as all areas of the cingulate cortex. Significant relative hypoperfusion was also apparent in the parahippocampal cortex, amygdala/entorhinal cortex, septal area and anterior thalamus, all of which showed medium to large effect sizes (d=0.6-0.8). No significant relative perfusion differences were detected in the basal forebrain, hypothalamus, mamillary bodies or orbitofrontal cortex. Logistic regression indicated that posterior cingulate cortex perfusion was able to discriminate AD patients from NC with 93% accuracy (95% sensitivity, 88% specificity). The current results suggest that most, but not all, limbic structures show significant relative hypoperfusion in AD. These findings validate previous post-mortem studies and could be useful in improving diagnostic accuracy, monitoring disease progression and evaluating potential treatment strategies in AD.

Topics: Aged; Alzheimer Disease; Female; Humans; Limbic System; Magnetic Resonance Imaging; Male; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Subtraction Technique; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The recent introduction of acetylcholinesterase inhibitors (AChEIs) therapy for Alzheimer's Disease (AD) has led to the need to assess the brain's response to the therapy on an objective, neurophysiological basis. Brain perfusion single photon emission computed tomography (SPECT) was used in an open-label study to evaluate the effect of chronic Donepezil administration to a group of patients affected by mild to moderate AD, compared to a group of AD patients not receiving AChEIs and kept under observation for a similar period.. Twenty-five consecutive patients with probable AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria) (19 women, 6 men; mean age: 74.2+/-7.2; mean Mini-Mental State Examination score, MMSE: 19.8+/-3.5) underwent (t0) brain SPECT with 99mTc-hexamethylpropylene-amine-oxime by a brain-dedicated, high-resolution camera and were re-evaluated (t1) after 11+/-2.6 months of chronic Donepezil administration (5mg/day) (treated group). Thirteen AD patients (9 women, 4 men, mean age: 71.4+/-5.7, MMSE score: 20.6+/-3.5) were not treated with AChEIs and served as controls (untreated group). They were subjected to the same evaluation after 13+/-1.4 months as the treated group. Statistical parametric mapping (SPM) was employed to analyse SPECT findings.. The MMSE score declined significantly (P<0.01) from t0 to t1 both in untreated (from 20.6+/-3.5 to 17.8+/-4.4) and in treated (from 19.8+/-3.5 to 17.8+/-4.1) group. At t(0), the untreated group showed higher regional cerebral blood flow (rCBF) than the treated group in a frontal and a frontal-parietal region of the left hemisphere. Between t0 and t1, significant rCBF reduction was observed in the temporal lobe and occipital-temporal cortex of the left hemisphere in the untreated group, whereas no significant change was observed in the treated group. The rCBF of the two groups did not significantly differ at t1. By covariate SPM analysis between t0 and t1 in treated patients, MMSE score changes correlated significantly with rCBF changes in a large left frontal-temporal region.. Brain perfusion is preserved in AD patients undergoing chronic Donepezil therapy while it is reduced in untreated patients. SPECT is a promising tool with which to assess the impact of AChEI therapy on brain functioning of AD patients.

Topics: Aged; Alzheimer Disease; Brain; Brain Mapping; Cholinesterase Inhibitors; Donepezil; Female; Humans; Indans; Male; Neuropsychological Tests; Piperidines; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The purpose of this study was to evaluate the effectiveness of activation versus baseline SPECT in detecting the regional cerebral blood flow (rCBF) changes in Alzheimer's disease (AD) patients after milameline (CI979/RU35926) treatment.. Ten patients with AD who took part in a milameline drug trial were examined by (99m)Tc-hexamethylpropyleneamine oxime SPECT before and after the medication. A split-dose technique was used for the acquisition of baseline and activation images within a single session. Two patients were unable to complete the activation challenges. rCBF changes were assessed using the statistical parametric mapping program. Both increased and decreased contrasts were used to test rCBF changes on activation and baseline images, respectively. rCBF changes caused by activation were also examined before and after milameline treatment.. Decreased rCBFs were observed at the temporal cortex on both sides of the brain and at the left parietal cortex on the activation SPECT images after milameline, whereas no statistically significant rCBF change was found on the baseline SPECT images. Memory stress caused not only increased rCBF in many areas of the brain, including the parietotemporal cortex, but also decreased rCBF at the splenium of the corpus callosum.. Cognitive activation scans are more effective than baseline scans in detecting rCBF changes in AD patients after milameline.

Topics: Alzheimer Disease; Brain; Cerebrovascular Circulation; Cognition; Dihydropyridines; Humans; Neuropsychological Tests; Oximes; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Mild cognitive impairment (MCI) was recently described as a heterogeneous group with a variety of clinical outcomes and high risk to develop Alzheimer's disease (AD). Regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) was used to study the heterogeneity of MCI and to look for predictors of future development of AD.. rCBF was investigated in 54 MCI subjects using Tc-99m hexamethylpropyleneamine oxime (HMPAO). An automated analysis software (BRASS) was applied to analyze the relative blood flow (cerebellar ratios) of 24 cortical regions. After the baseline examination, the subjects were followed clinically for an average of two years. 17 subjects progressed to Alzheimer's disease (PMCI) and 37 subjects remained stable (SMCI). The baseline SPECT ratio values were compared between PMCI and SMCI. Receiver operating characteristic (ROC) analysis was applied for the discrimination of the two subgroups at baseline.. The conversion rate of MCI to AD was 13.7% per year. PMCI had a significantly decreased rCBF in the left posterior cingulate cortex, as compared to SMCI. Left posterior cingulate rCBF ratios were entered into a logistic regression model for ROC curve calculation. The area under the ROC curve was 74%-76%, which indicates an acceptable discrimination between PMCI and SMCI at baseline.. A reduced relative blood flow of the posterior cingulate gyrus could be found at least two years before the patients met the clinical diagnostic criteria of AD.

Topics: Alzheimer Disease; Blood Flow Velocity; Cerebrovascular Circulation; Cognition Disorders; Disease Progression; Female; Follow-Up Studies; Gyrus Cinguli; Humans; Logistic Models; Male; Middle Aged; Neuropsychological Tests; Predictive Value of Tests; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Characteristic patterns of regional cerebral blood flow (rCBF) reduction, as detected by technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO) single-photon emission tomography (SPET), may help clinicians in differentiating patients with frontotemporal dementia (FTD) from those with Alzheimer's disease (AD). However, in some cases these patients may share common rCBF abnormalities and the visual analysis and/or the region of interest (ROI) approach may not sensitively detect more localised focal changes that could be more specific for each pathology. Recently, automated voxel-by-voxel statistical analysis of perfusion brain maps has been applied to SPET images. This method has the advantage of including the rCBF information for the whole brain for statistical analysis without any a priori hypothesis regarding the regions possibly involved. This could result in a better characterisation of rCBF differences in brain regions while also reducing the operator's subjectivity and the time required for data analysis. The purpose of this study was to apply such a technique to highlight the specific brain areas showing a relative functional involvement in FTD and AD. Thus, we compared the relative rCBF patterns obtained in eight FTD patients with those obtained in 21 AD patients using (99m)Tc-HMPAO SPET and statistical parametric mapping (SPM). When FTD patients were compared with AD patients, relatively lower rCBF was observed in right medial frontal cortex (BA 8, 9, 10), right anterior cingulate cortex (BA 32), right temporal cortex (BA 21/22), right orbitofrontal cortex (BA 11) and ventrolateral prefrontal cortex (BA 47); in BA 47 the reduction was evident bilaterally but was more marked on the right side. On the other hand, when AD patients were compared with FTD patients, a significant relative rCBF decrease was found in the bilateral superior parietal cortex (BA 7); this decrease was more extensive on the left side, where it also included the inferior parietal (BA 40), superior occipital (BA 19) and temporo-occipital regions (BA 39, 19). The results of this study confirm the preferential involvement of the frontotemporal regions in FTD patients and of the temporoparietal regions in AD patients. Furthermore, they highlight the networks that are more specifically impaired in these disorders and that could be implicated in the emotional-behavioural and cognitive disturbances that characterise FTD and AD respectively.

Topics: Aged; Alzheimer Disease; Cerebral Cortex; Cerebrovascular Circulation; Dementia; Female; Humans; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Male; Nerve Net; Radiopharmaceuticals; Subtraction Technique; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Methods for quantifying the changes in brain function observed in single photon emission computed tomography (SPECT) using hexamethylenepropylene amine oxime (HMPAO) for patients with Alzheimer's disease have the potential of improving the diagnostic accuracy of the procedure and its ability to monitor response to treatment. The absolute percentage uptake of HMPAO and the cerebral perfusion volume (CPV) of the brain were assessed using SPECT in 26 patients with mild to moderate Alzheimer's disease (AD) and 24 control subjects. A subset of 15 control subjects, which was age-matched to the AD patients, was selected to allow fair statistical comparison of parameters between groups. The percentage of brain volume with reduced perfusion (R) and a volume loss index (VLI), given by /CPV, were also calculated. Eight of the control subjects were studied on a second occasion after a mean period of 6 months. There was no significant difference in percentage uptake between controls and AD patients, the mean value being 5.8%. Cerebral perfusion volume in controls was found to depend on sex (mean value in males and females being 1327 ml and 1222 ml, respectively) and on age. The volume loss index corrected for age and sex provided good discrimination between controls and AD subjects giving a sensitivity and specificity of 81% and 96%, respectively. The repeatability coefficient, the 95% confidence limit for the difference between repeat measurements, on controls was 67 ml (5%). The measurement of cerebral perfusion volume and related indices may be of value in identifying patients with early Alzheimer's disease and in following their response to treatment.

Topics: Adult; Aged; Aged, 80 and over; Aging; Alzheimer Disease; Brain; Cerebrovascular Circulation; Female; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Predictive Value of Tests; Radiopharmaceuticals; Sex Factors; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Twenty seven patients with mild AD were enrolled in a prospective open label controlled study of rivastigmine. Assessments included a range of neuropsychiatric and behavioural measures and rCBF using HMPAO SPECTat baseline, three and six months. Significant enhancement of frontal, parietal and temporal brain blood flow with related psychometric improvement was observed in twelve of the treated patients. A pattern of reduced rCBF and cognitive performance was observed in four unresponsive and eleven untreated patients. The results suggest that alterations in the clinical and cognitive status of patients receiving a cholinesterase inhibitor are paralleled by changes in rCBF. Longitudinal assessment with repeated imaging offers a method of better understanding the effects of cholinesterase inhibition on the AD brain.

Topics: Aged; Alzheimer Disease; Carbamates; Cerebrovascular Circulation; Cholinesterase Inhibitors; Cluster Analysis; Cognition; Female; Humans; Longitudinal Studies; Male; Neuropsychological Tests; Phenylcarbamates; Prospective Studies; Radiopharmaceuticals; Rivastigmine; Technetium Tc 99m Exametazime; Time Factors; Tomography, Emission-Computed, Single-Photon

Differences in regional cerebral blood flow (rCBF) between subjects with Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and healthy volunteers were investigated using statistical parametric mapping (SPM99). Forty-eight AD, 23 DLB and 20 age-matched control subjects participated. Technetium-99m hexamethylpropylene amine oxime (HMPAO) brain single-photon emission tomography (SPET) scans were acquired for each subject using a single-headed rotating gamma camera (IGE CamStar XR/T). The SPET images were spatially normalised and group comparison was performed by SPM99. In addition, covariate analysis was undertaken on the standardised images taking the Mini Mental State Examination (MMSE) scores as a variable. Applying a height threshold of P < or = 0.001 uncorrected, significant perfusion deficits in the parietal and frontal regions of the brain were observed in both AD and DLB groups compared with the control subjects. In addition, significant temporoparietal perfusion deficits were identified in the AD subjects, whereas the DLB patients had deficits in the occipital region. Comparison of dementia groups (height threshold of P < or = 0.01 uncorrected) yielded hypoperfusion in both the parietal [Brodmann area (BA) 7] and occipital (BA 17, 18) regions of the brain in DLB compared with AD. Abnormalities in these areas, which included visual cortex and several areas involved in higher visual processing and visuospatial function, may be important in understanding the visual hallucinations and visuospatial deficits which are characteristic of DLB. Covariate analysis indicated group differences between AD and DLB in terms of a positive correlation between cognitive test score and temporoparietal blood flow. In conclusion, we found evidence of frontal and parietal hypoperfusion in both AD and DLB, while temporal perfusion deficits were observed exclusively in AD and parieto-occipital deficits in DLB.

Topics: Age Factors; Aged; Alzheimer Disease; Brain; Cerebrovascular Circulation; Diagnosis, Differential; Female; Humans; Image Enhancement; Lewy Body Disease; Male; Models, Statistical; Radiopharmaceuticals; Reference Values; Reproducibility of Results; Sensitivity and Specificity; Sex Factors; Statistics as Topic; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The development of cholinergic therapies for Alzheimer's disease (AD) has highlighted the importance of understanding the role of attentional deficits and the relationship between attention and memory in the earliest stages of the disease. Variability in the tasks used to examine aspects of attention, and in the disease severity, between studies makes it difficult to determine which aspects of attention are affected earliest in AD, and how attentional impairment is related to other cognitive modules. We tested 27 patients in the early stages of the disease on the basis of the MMSE (minimal 24-30 corresponding to minimal cognitive impairment, very mild or possible AD in other classifications; and mild 18-23) on a battery of attentional tests aimed to assess sustained, divided, and selective attention, plus tests of episodic memory, semantic memory, visuoperceptual and visuospatial function, and verbal short-term memory. Although the mildly demented group were impaired on all attentional tests, the minimally impaired group showed a preserved ability to sustain attention, and to divide attention based on a dual-task paradigm. The minimally demented group had particular problems with response inhibition and speed of attentional switching. Examination of the relationship between attention and other cognitive domains showed impaired episodic memory in all patients. Deficits in attention were more prevalent than deficits in semantic memory suggesting that they occur at an earlier stage and the two were partially independent. Impairment in visuoperceptual and visuospatial functions and verbal short-term memory were the least common. Although attention is impaired early in AD, 40% of our patients showed deficits in episodic memory alone, confirming that amnesia may be the only cognitive deficit in the earliest stages of sporadic AD.

Topics: Aged; Alzheimer Disease; Attention; Disease Progression; Female; Follow-Up Studies; Humans; Intelligence Tests; Male; Memory Disorders; Neuropsychological Tests; Psychomotor Performance; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To investigate why bilateral parietotemporal hypoperfusion, the typical SPECT pattern of Alzheimer's disease (AD), occurs in some but not in all patients with probable AD.. We reviewed the SPECT scans of 220 patients presenting with cognitive impairment. Among them, 104 patients fulfilled NINCDS-ADRDA criteria for probable AD, 48 (32 women) with early onset (before age of 65) and 56 (40 women) with late onset of the symptoms. Dementia severity was assessed by the Mini-Mental State Examination. The SPECT scans were classified by visual inspection blind to clinical diagnoses.. Bilateral parietotemporal hypoperfusion was more frequent in patients with severe AD, in those with early onset of the symptoms, and in men. Duration of symptoms, type of gamma-camera or radiopharmaceutical agent used were not associated with this SPECT pattern.. These findings may be useful in the clinical setting and point to heterogeneity of AD according to age at onset.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognition Disorders; Cysteine; Double-Blind Method; Female; Functional Laterality; Humans; Male; Middle Aged; Neuropsychological Tests; Organotechnetium Compounds; Parietal Lobe; Radiopharmaceuticals; Severity of Illness Index; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

Alzheimer's disease is associated with a loss in presynaptic cholinergic function. It has been suggested that cholinergic inhibitors such as donepezil hydrochloride (Donepezil) could restore this function and improve some of the symptoms of Alzheimer's disease. Previous work has shown that Donepezil improves cognitive and global function in patients with mild to moderate Alzheimer's disease. This study reviewed retrospectively 12 patients who had previously had a 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) single photon emission tomography (SPET) regional cerebral blood flow (rCBF) examination and had gone on to receive Donepezil therapy. These patients were recalled for a further 99Tcm-HMPAO SPET rCBF examination and the image data sets were compared. The results showed an overall increase in global cerebral blood flow (P = 0.04) averaged over the group with a percentage change in blood flow ranging from -1.8% to 6.4%. However, some patients showed a slight decrease in blood flow. When the data were analysed in terms of regional cerebral blood flow, we found that the most significant increase in blood flow occurred in the frontal lobes (P = 0.02).

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cerebrovascular Circulation; Donepezil; Female; Humans; Image Processing, Computer-Assisted; Indans; Magnetic Resonance Imaging; Male; Middle Aged; Nootropic Agents; Piperidines; Radiopharmaceuticals; Retrospective Studies; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Psychotic symptoms are produced by distributed neuronal dysfunction. Abnormalities of reality testing and false inference implicate frontal lobe abnormalities.. To identify the functional imaging profile of patients with Alzheimer's disease manifesting psychotic symptoms as measured by single photon emission computed tomography (SPECT).. Twenty patients with Alzheimer's disease who had SPECT and clinical evaluations were divided into two equal groups with similar mini mental status examination (MMSE), age, sex, and the range of behaviours documented by the neuropsychiatric inventory (NPI), except delusions and hallucinations. SPECT studies, registered to a probabilistic anatomical atlas, were normalised across the combined group mean intensity level, and subjected to a voxel by voxel subtraction of the non-psychotic minus psychotic groups. Subvolume thresholding (SVT) corrected random lobar noise to produce a three dimensional functional significance map.. The significance map showed lower regional perfusion in the right and left dorsolateral frontal, left anterior cingulate, and left ventral striatal regions along with the left pulvinar and dorsolateral parietal cortex, in the psychotic versus non-psychotic group.. Patients with Alzheimer's disease who manifest psychosis may have disproportionate dysfunction of frontal lobes and related subcortical and parietal structures.

Topics: Alzheimer Disease; Brain Mapping; Cerebrovascular Circulation; Corpus Striatum; Delusions; Female; Frontal Lobe; Gyrus Cinguli; Hallucinations; Humans; Male; Parietal Lobe; Psychotic Disorders; Sex Factors; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The hippocampus is involved in Alzheimer's disease (AD) and regulates the hypothalamus-pituitary-adrenal axis (HPAA). Enhanced cortisol secretion has been reported in AD. Increased cortisol levels affect hippocampal neuron survival and potentiate beta-amyloid toxicity. Conversely, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are believed to antagonize noxious glucocorticoid effects and exert a neuroprotective activity. The present study was aimed at investigating possible correlations between hippocampus perfusion - evaluated by SPECT - and HPAA function in AD. Fourteen patients with AD and 12 healthy age-matched controls were studied by (99m)Tc-HMPAO high-resolution brain SPECT. Plasma adrenocorticotropin, cortisol, and DHEAS levels were determined at 2.00, 8.00, 14.00, 20.00 h in all subjects and their mean values were computed. Cortisol/DHEAS ratios (C/Dr) were also calculated. Bilateral impairment of SPECT hippocampal perfusion was observed in AD patients as compared to controls. Mean cortisol levels were significantly increased and DHEAS titers were lowered in patients with AD, as compared with controls. C/Dr was also significantly higher in patients. Using a stepwise procedure for dependent SPECT variables, the variance of hippocampal perfusional data was accounted for by mean basal DHEAS levels. Moreover, hippocampal SPECT data correlated directly with mean DHEAS levels, and inversely with C/Dr. These data show a relationship between hippocampal perfusion and HPAA function in AD. Decreased DHEAS, rather than enhanced cortisol levels, appears to be correlated with changes of hippocampal perfusion in dementia.

Topics: Adrenocorticotropic Hormone; Aged; Aged, 80 and over; Alzheimer Disease; Cerebrovascular Circulation; Dehydroepiandrosterone Sulfate; Female; Hippocampus; Humans; Hydrocortisone; Male; Middle Aged; Pituitary-Adrenal System; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The authors retrospectively explored the behavioral and functional imaging profile of Alzheimer's disease (AD) patients who respond to cholinesterase inhibitor therapy by using the Neuropsychiatric Inventory (NPI) and baseline [99mTc]HMPAO SPECT. Thirty AD patients were divided into three groups (Responders, Nonresponders, and Unchanged) based on their behavioral response to donepezil. Responders had significantly (P < or = 0.01) more pretreatment irritability, disinhibition (P < or = 0.05), and euphoria (P = 0.05) than Nonresponders and significantly lower lateral orbital frontal (P < 0.00001) and dorsolateral frontal (P < or = 0.0005) perfusion bilaterally. A pretreatment orbitofrontal syndrome may predict behavioral response to cholinesterase inhibitor therapy in AD.

Topics: Aged; Alzheimer Disease; Behavior; Cerebrovascular Circulation; Cholinesterase Inhibitors; Double-Blind Method; Female; Frontal Lobe; Humans; Image Processing, Computer-Assisted; Male; Psychiatric Status Rating Scales; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Trichlorfon

Early diagnosis in Alzheimer's disease (AD) is important for the administration of new treatments. The purpose of this study was to differentiate mildly/moderately demented AD patients from normal controls by means of activational brain SPECT, and to investigate the correlation between regional cerebral blood flow and dementia severity. Activational brain SPECT was performed 1 week after basal brain SPECT in 12 mild/moderate AD patients according to NINCDS-ADRDA criteria (mean age 69+/-7 years) and in seven healthy, age-matched, volunteer controls (mean age 65+/-9 years). In order to activate the parietal cortex, patients were asked to subtract serial 5's from 100, 2 min before and after the intravenous administration of 925 MBq technetium-99m labelled D,L-hexamethyl-propylene amine oxime (99Tcm-HMPAO). Using a three-headed gamma camera equipped with high resolution collimators, 128 images of 35 s duration in a 64 x 64 matrix were obtained over 360 degrees. Region to whole brain ratios (R/WB) were calculated in three consecutive transaxial slices 2 pixels thick above the orbitomeatal line, and the activation percentage was calculated. No statistical difference was detected between AD patients and normal controls for parietal cortex activation. The correlation coefficient between the Mini-Mental State Examination (MMSE) scoring and the activation percentage was 0.475 in normal controls and 0.175 in AD patients for the left anterior parietal cortex, and 0.353 in normal controls and 0.146 in AD patients for the right anterior parietal cortex. In a visual evaluation of parietal cortex activation, 50% of AD patients were able to activate the parietal cortex, whereas 86% of the normal controls could do so. In our current study, the subtraction of serial 5's was not regarded as a promising task. Further studies are needed to clarify the importance of such tasks in the differential diagnosis of mild/moderate AD patients from normal elderly.

Topics: Aged; Alzheimer Disease; Brain; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Parietal Lobe; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Delusional thinking and related behaviours are common symptoms in Alzheimer's disease (AD). The aim of the study was to determine if any consistent cerebral image pattern can be identified using Tc99m-hexamethylpropyleneamine (HMPAO) SPET in AD patients with and without delusions. 18 AD patients with delusion and 15 AD patients without delusion underwent neuropsychological testing and regional cerebral blood flow imaging using Tc99m-HMPAO SPET. The reconstructed data was compared using regions of interest drawn over each cerebral lobe and a statistical parametric mapping (SPM) approach. The neuropsychological testing showed that there was no difference in the profiles of the deluded and non deluded AD patients. The imaging results showed a significant degree of image asymmetry. This took the form of a right hemisphere hypoperfusion mainly in the right frontal and limbic regions. The results do not indicate a specific focal site of hypoperfusion in the patients with delusion. They do, however, indicate that delusions in AD may be associated with areas of hypoperfusion in the right anterior hemisphere.

Topics: Aged; Alzheimer Disease; Brain Mapping; Cerebrovascular Circulation; Delusions; Female; Functional Laterality; Humans; Image Processing, Computer-Assisted; Male; Neuropsychological Tests; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To evaluate the accuracy of Single Photon Emission Computed Tomography (SPECT) scanning in the diagnosis of Alzheimer's Disease (AD) and its capacity to improve the diagnostic accuracy of conventional clinical evaluation.. Comparison of SPECT scanning of AD and normal subjects with the criterion standard of clinical diagnosis confirmed by 1-year repeated evaluation.. A memory clinic in a tertiary care university hospital.. One hundred twenty patients were evaluated upon entering the Jewish General Hospital (McGill University) Memory Clinic. Fifty-eight patients were diagnosed as having AD and 17 as having vascular dementia. Twenty unmatched controls (recruited mainly through newspaper advertisements) were normal, and 25 had cognitive impairment without dementia (not included in the statistical analysis).. Comparison of visual inspection of SPECT, based on the system of classification developed by Holman et al., using B pattern alone as positive or B (bilateral posterior temporal and/or parietal cortex deficits) or C (bilateral posterior temporal and/or parietal deficits with additional defects) pattern and B or C or D (unilateral posterior temporal and/or parietal defects with or without additional defects) as positive compared with clinical diagnosis after repeated evaluations. Sensitivity and specificity, as well as positive predictive value (PPV) and negative predictive value (NPV) based on the prevalence of AD in a memory clinic setting of 30% or 50%, were calculated.. With B pattern as positive, the sensitivity of SPECT was 21% whereas the specificity was 80%. With B or C as positive, the sensitivity was 29% and the specificity was 75%. With B or C or D as positive, the sensitivity was 55% and the specificity was 65%. With a 30% prevalence, the PPV with B pattern as positive was 31% whereas the NPV was 30%. The PPV with B or C as positive was 33% while the NPV was 29%, and the PPV with B or C or D as positive was 40% whereas the NPV was 23%. With a 50% prevalence, the PPV with B pattern as positive was 51% and the NPV 49.6%; the PPV with B or C as positive was 54% and the NPV 48.6%; the PPV with B or C or D as positive was 61% while NPV was 41%.. The sensitivity and specificity were too low for SPECT to be useful as a diagnostic test for AD. The poor positive and negative predictive values in our tertiary care clinic mean that SPECT is not useful in "ruling-in" or "ruling-out" AD in that setting. In fact, clinical evaluation is more accurate.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Diagnosis, Differential; Female; Humans; Intelligence Tests; Male; Middle Aged; Organotechnetium Compounds; Oximes; Predictive Value of Tests; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Vascular Diseases

Thirty-nine patients with probable Alzheimer's disease (AD) were studied with [99mTc]HMPAO SPECT and a standardized neuropsychological battery testing intellect, memory, attention, language, motor and praxis functions, and depression. Spearman rank correlations and multivariate regression analyses were performed to correlate quantitative regional perfusion deficits to these tests. Patients were found to have decreased perfusion of left frontal, parietal, and temporal regions relative to right. WAB repetition scores and bilateral temporal flow were significantly correlated (P < 0.01). Correlations between visual memory and bilateral temporal flow and those between Mini-Mental State/ Geriatric Depression Scale scores and bihemispheric flow approached significance. Although in this study regional cerebral blood flow was relatively insensitive to neuroanatomical abnormalities underlying specific cognitive deficits, it may have some specificity for identifying the language disorder in AD.

Topics: Aged; Alzheimer Disease; Attention; Cerebrovascular Circulation; Cognition; Female; Humans; Intelligence Tests; Male; Memory; Multivariate Analysis; Neuropsychological Tests; Organotechnetium Compounds; Oximes; Perfusion; Psychiatric Status Rating Scales; Psychometrics; Psychomotor Performance; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

This study investigated the hypothesis that the combination of regional CT brain atrophy measurements and semiquantitative SPECT regional blood flow ratios could produce a diagnostic test for Alzheimer's disease (AD) with an accuracy comparable to that achieved with the present clinical gold standard of the NINCDS-ADRDA criteria.. Single proton emission computed tomography (SPECT) and CT head scans were performed on 122 subjects referred an UBC Alzheimer clinic and diagnosed as either 'not demented' (ND-37) or 'possible/probable AD' (AD-85) by the NINCDS-ADRDA criteria. Stepwise discriminant analysis (SDA) was performed on the bilateral SPECT regions of interest and compared to bilateral CT qualitative/quantitative assessment in the frontal, parietal and temporal lobes to determine which were most accurate at ND/AD distinction. Receiver operating curves (ROC) were then constructed for these variables individually and for their combined discriminant function.. The left temporal qualitative cortical atrophy score (CT) and left temporal perfusion ratio (SPECT) were selected in the SDA. The combined discriminant function was more specific at AD/ND distinction than either of CT or SPECT alone. The accuracy of AD/ND distinction with the combined discriminant function was below that achieved by clinical diagnosis according to the NINCDS-ADRDA criteria and was not significantly different from that achieved with SPECT or CT alone as defined by ROC curve analysis.. The measurements of left temporal cortical atrophy and regional cerebral blood flow were most indicative of AD; however they lacked the sensitivity and specificity to recommend their use as a diagnostic test for AD.

Topics: Aged; Alzheimer Disease; Atrophy; Brain; Cerebral Cortex; Cerebrovascular Circulation; Female; Functional Laterality; Humans; Male; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Cerebral blood flow (CBF) at rest was measured by 123I-IMP SPECT and the standing test was conducted by 99mTc-HMPAO SEPCT in patients with dementia of Alzheimer's type (DAT) and vascular dementia (VD) in order to evaluate cerebral autoregulation and to consider the diagnostic significance of this determination and test. CBF at rest decreased significantly in all regions in the DAT and VD groups compared to the control groups (healthy aged persons, group C). The value of mean CBF also decreased significantly in the DAT (40.1 micromilligrams/100 g/min) and VD groups (41.3) as compared to group C (51.0). In the DAT groups, the CBF was significantly lower in the parietal region compared to VD groups, and CBF and Hasegawa's dementia score showed a positive correlation in the temporal and parietal regions. Decreases in blood pressure upon standing were about 10 mmHg in all three groups, but the decrease rate in mean CBF was significantly greater in the VD groups (20.2%) than in the C (5.0%) and DAT groups (4.0%). The dysautoregulation index (D.I. delta; % CBF mmHg), used as a measurement of cerebral autoregulation, was significantly higher in the VD groups (1.7) than in the C(0.5) and DAT groups (0.3). This index made it possible to make differential diagnosis in some patients in whom it was impossible using CBF at rest, probably due to impaired cerebral autoregulation and atherosclerotic changes in VD patients. Our findings suggest that D.I. provides information on the condition of patients that cannot be obtained with CBF at rest and assists in differential diagnosis.

Topics: Aged; Alzheimer Disease; Amphetamines; Brain; Cerebrovascular Circulation; Dementia, Vascular; Female; Hemodynamics; Humans; Iodine Radioisotopes; Iofetamine; Male; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Imaging of local cerebral blood flow (lCBF) may serve as an important supplementary tool in the aetiological assessment of dementias. In early or preclinical disease, however, there are less characteristic changes in lCBF. In the present study it was investigated whether vasoactivation or neuroactivation may produce more pronounced local lCBF deficits. Local CBF was investigated by using technetium-99m hexamethylpropylene amine oxime and single-photon emission tomography (SPET) in 80 patients (50 with mild cognitive impairment and 30 with dementia of Alzheimer type (DAT), all without evidence of cerebrovascular disease) at rest (baseline) and during activation. In 31 studies patients underwent vasomotor activation with acetazolamide, while 62 studies were performed under cognitive challenge (neuroactivation by labyrinth task). Cortical activity relative to that of cerebellum increased significantly in a right temporal region and tended to increase in other cortical regions upon vasoactivation. In contrast, neuroactivation reduced cortical activity relative to that of cerebellum in several left and right temporal and in left parietal regions. Visual classification of SPET images of patients with probable DAT by three observers resulted in a reduction of the number of definitely abnormal patterns from 9/12 to 4/12 by vasoactivation and an increase from 10/18 to 15/18 by neuroactivation. Correspondingly, abnormal ratings in patients with mild cognitive dysfunction were reduced from 7/19 to 5/19 by vasoactivation and were increased from 12/21 to 18/21 by neuroactivation. In conclusion, vasoactivation does not enhance local relative perfusion deficits in patients with cognitive impairment of non-vascular aetiology, whereas neuroactivation by labyrinth task produces more pronounced local flow differences and enhances abnormal patterns in lCBF imaging.

Topics: Acetazolamide; Aged; Alzheimer Disease; Brain; Cerebrovascular Circulation; Cognition Disorders; Female; Humans; Male; Organotechnetium Compounds; Oximes; Task Performance and Analysis; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The authors examined the presence of specific quantified electroencephalographic (qEEG) changes in dementia patients with relatively lower frontal or parietal blood perfusion as demonstrated by SPECT. Over all brain regions, patients with relatively lower parietal perfusion showed significantly higher theta relative power than demented patients with relatively lower frontal perfusion or normal control subjects. Dementia patients with relatively lower frontal perfusion showed no differences from age-comparable normal control subjects in qEEG variables. These findings 1) suggest that usefulness of qEEG for the diagnosis of dementia is restricted to a subgroup of patients with the typical SPECT pattern of parietal blood hypoperfusion and 2) demonstrate that the qEEG changes typical of dementia are not related to perfusion deficits in frontal brain areas.

Topics: Aged; Alzheimer Disease; Cerebrovascular Circulation; Dementia; Electroencephalography; Female; Fourier Analysis; Frontal Lobe; Humans; Male; Neurologic Examination; Neuropsychological Tests; Organotechnetium Compounds; Oximes; Parietal Lobe; Psychiatric Status Rating Scales; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Alzheimer's disease (AD) is a heterogeneous entity. Identifying AD subtypes might have impact in patients' response to different treatment strategies. We designed a study to examine regional cerebral blood flow (rCBF) in AD subtypes. To identify AD subtypes, we performed a cluster analysis including performance on memory, language, visuospatial, praxic, and executive functions. The rCBF measured by 99mTc-HMPAO SPECT was referred to the cerebellum. We examined 35 patients fulfilling the NINCDS-ADRDA criteria of probable AD and 13 age and sex-matched healthy cognitively intact controls. AD patients were at the early stage of the disease, their mean Mini-Mental Status (MMS) score (S.D.) was 22.5 (3.6). The cluster analysis revealed two AD subgroups: AD1 (N = 12) and AD2 (N = 23). The subgroups did not differ in age, sex, or global clinical severity as assessed by MMS and Brief Cognitive Rating Scale (BCRS). Both subgroups had equally impaired memory. The AD2 group was inferior to the AD1 group on verbal, visuospatial, praxic, and executive functions. The AD1 group showed reduced rCBF ratios in the temporal and parietal cortices and the amygdala compared to controls. The AD2 group differed from controls in the rCBF ratios of frontal, temporal, parietal, occipital, basal ganglia, and amygdaloid regions bilateral and from AD1 in the rCBF ratios of frontal and temporal cortices. In AD patients, the rCBF ratios did not correlate with MMS or BCRS scores. In contrast, several significant correlations were found between decreases rCBF ratios and impairment of memory and other cognitive functions. In conclusion, a cluster analysis on neuropsychological test performance identified two AD subgroups that differed on the neuropsychological profile and on the rCBF in spite of similar global clinical severity.

Topics: Aged; Alzheimer Disease; Cerebrovascular Circulation; Cognition; Cognition Disorders; Female; Humans; Language; Male; Memory; Neuropsychological Tests; Organotechnetium Compounds; Oximes; Psychomotor Performance; Space Perception; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

This study was designed to evaluate, whether investigations of cerebral blood flow can be a helpful diagnostic tool in the differential diagnosis between (senile) dementia of Alzheimer's type [(S)DAT] and geriatric depression with cognitive impairment. Under clinical routine conditions we performed Single Photon Emission Computed Tomography (SPECT) using 99mTc-Hexamethylpropyleneamine Oxime (HMPAO) in 23 patients with (S)DAT (14f, 9m; mean age 68.9 y), 17 patients with geriatric depression (9 f, 8 m; mean age 66.4 y) and 12 age-matched controls (9 f, 3 m; mean age 69.2 y). Semiquantitative analysis (corticocerebellar ratios) of eight different regions of interest (ROI) revealed a significantly (p < 0.05) reduced perfusion in the (S)DAT patients compared to the control group. The depression group exhibited perfusion values between the (S)DAT and control group. The difference between the depression and (S)DAT group was most prominent in the left parieto-occipital ROI (p = 0.008). We discuss the data with extensive regard to the literature and conclude that 99mTc-HMPAO SPECT is a valuable additional tool in the differential diagnosis of depression and dementia in the elderly.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cerebrovascular Circulation; Depressive Disorder; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Psychiatric Status Rating Scales; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

In a prospective MRI study the presence, appearance, volume, and regional cerebral blood flow (rCBF) correlates of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) were examined in 18 patients with probable Alzheimer's disease and in 10 age matched healthy control subjects, all without major cerbrovascular risk factors. The 133Xe inhalation method and the [99mTc]-d,l-hexamethyl-propylene-amine-oxime (HMPAO) technique with single photon emission computed tomography (SPECT) were used to measure rCBF. Rating scores for PVHs were significantly higher in the Alzheimer's disease group (p < 0.01) and correlated significantly with the volume of ventricles (p < 0.05) and with systolic arterial blood pressure (p < 0.01), but not with rCBF. By contrast, there was no significant difference in the rating scores or volumes of DWMHs between the two groups, although three patients had extensive DWMH lesions in the central white matter. In the group of patients with Alzheimer's disease as a whole, the volume of DWMHs correlated well with rCBF in the hippocampal region ( r = -0.72; p < 0.001), but not with frontal, temporal, parietal, or occipital rCBF. Postmortem histopathology of extensive DWMH lesions in one patient with definite Alzheimer's disease showed a partial loss of myelin and astrocytic gliosis, but no ischaemic changes. It is concluded that DWMH lesions may be associated with reduced rCBF in the hippocampal region. The heterogenous topography of neocortical rCBF deficits in Alzheimer's disease could not be explained by deafferentation from underlying white matter hyperintensities and therefore may reflect variations in the topography of cortical abnormalities.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Blood Flow Velocity; Blood Pressure; Case-Control Studies; Cerebral Ventricles; Cerebrovascular Circulation; Dementia; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Matched-Pair Analysis; Middle Aged; Organotechnetium Compounds; Oximes; Prospective Studies; Regional Blood Flow; Severity of Illness Index; Systole; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Xenon Radioisotopes

The shape, size and location of regions of interest (ROIs) show considerable variability between single-photon emission tomography (SPET) studies in aging and Alzheimer's disease, but the possible influence on study results remains unknown. We compared three different ROIs in a SPET study with 60 controls and in 48 patients with probable Alzheimer's disease diagnosed according to the NINCDS-ADRDA criteria. Regional cerebral blood flow (rCBF) was assessed with SPET using technetium-99m d,l-hexamethylpropylene amine oxime (99mTc-HMPAO), normalized to the mean activity in a cerebellar reference slice. The three different ROIs were: a multi-slice and a single-slice ROI with reference to the normal brain anatomy (using an anatomical atlas), and a rectangular (2 x 4 pixels) ROI in the frontal, temporal, temporoparietal and occipital cortices. No differences were observed for the means of rCBF values between the single-slice and multi-slice ROI's with reference to the normal anatomy, but some variability was present for individual comparisons. In contrast, significantly higher mean rCBF values were obtained with the single-slice rectangular ROIs in all four regions for both patients and controls and considerable variability was shown for individual subjects. After analysis with multivariate logistic regression and receiver operator characteristic curves, the ability of SPET to discriminate between controls and Alzheimer patients was similar in the three methods for mild and moderate Alzheimer patients (Global Deterioration Scale = GDS of 3 and 4). However, with increasing dementia severity (GDS > 4) the rectangular ROIs showed lower ability to discriminate between groups compared to the single-slice and multi-slice anatomically defined ROIs.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aging; Alzheimer Disease; Brain; Cerebrovascular Circulation; Female; Humans; Linear Models; Male; Organotechnetium Compounds; Oximes; ROC Curve; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Positron emission tomography (PET) of 18F-2-fluoro-2-deoxy-D-glucose (FDG) and single-photon emission tomography (SPET) of 99mTc-hexamethylpropylene amine oxime (HMPAO) were performed under identical resting conditions within 3 h in 20 patients with probable Alzheimer's disease (AD), 12 patients with vascular dementia (VD) and 13 normal persons. In the temporoparietal association cortex similar impairment of relative regional cerebral glucose metabolism (rCMRGl) and relative HMPAO uptake (rCBF) was found. In addition PET showed hypometabolism in the occipital association cortex. The functional pattern was condensed to a ratio of regional values of association areas divided by regional values of structures that are typically less affected by AD. In normals this ratio was significantly related to age for PET metabolic data (r = -0.66, P = 0.01). The ratio was significantly lower in AD than in VD and controls for both rCMRGl and rCBF. In AD only, the metabolic ratio was related to severity of dementia (r = 0.54, P = 0.003) and age (r = 0.64, P = 0.003). Metabolic differences between normals and AD patients were less obvious in old age. In contrast, there were no significant correlations between the perfusion ratio and severity of dementia or age. Comparing the metabolic and perfusion ratio by receiver operating characteristic curves, PET differentiated AD from normals only marginally better than SPET. Differentiation between AD and VD was much better achieved by PET. Our results suggest that both PET and SPET can distinguish AD patients from controls, whereas for differentiation between AD and VD SPET is of little value.

Topics: Aged; Aging; Alzheimer Disease; Brain; Cerebrovascular Circulation; Dementia, Vascular; Deoxyglucose; Diagnosis, Differential; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Glucose; Humans; Male; Organotechnetium Compounds; Oximes; ROC Curve; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

A new method for the analysis of regional cerebral blood flow (rCBF) studies, the 'Min-Max' method, was compared with the conventional method, the 'Average' method. Regional CBF was examined by single photon emission computed tomography (SPECT) using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO). The two methods were used to quantify the rCBF in a population of patients with various dementia disorders, and in healthy controls. Results from a phantom were also used. In the Average method the average counts per pixel (cp-1) within irregular manually drawn regions of interest (ROIs) was registered. In the Min-Max method the minimum cp-1 and maximum cp-1 within rectangular ROIs were registered for white and grey matter, respectively. The relative rCBF (rrCBF) was calculated as the ratio between the regional and cerebellar values. The Min-Max method gave systematically lower values for rrCBF in the white matter, in both clinical studies, and in the phantom, compared to the Average method. No difference was found in the grey matter results. The variability in rrCBF in the phantom study was greater with the Min-Max method than with the Average method, but this effect was counteracted in the clinical studies by a smaller interobserver error. The average regional differences between patients and controls appeared greater with the Min-Max method than with the Average method. The Min-Max method proved to be more simple to execute, involved a smaller observer error, and with respect to ability to distinguish patients with dementia disorders from controls, it appears to function at least as well as the accepted Average method.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Cerebrovascular Circulation; Dementia; Dementia, Multi-Infarct; Humans; Hydrocephalus, Normal Pressure; Middle Aged; Models, Structural; Organotechnetium Compounds; Oximes; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Neuroimaging with [2,2-dimethyl-3-[(2R,3E)-3-oxidoiminobutan-2-yl]azanidylpropyl]-[(2R,3E)-3-hydroxyiminobutan-2-yl]azanide;oxo(

Topics: Alzheimer Disease; Animals; Brain; Cerebrovascular Circulation; Humans; Mice; Organotechnetium Compounds; Perfusion; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To explore differences of apathy perfusion correlates between Alzheimer's disease (AD) and Frontotemporal dementia (FTD) using perfusion SPECT.. We studied 75 FTD and 66 AD patients. We evaluated apathy using Neuropsychiatric Inventory (NPI). We compared perfusion of BAs on left (L) and right (R) hemisphere in AD and FTD.. Apathy in AD was significantly and negatively correlated with dorsolateral prefrontal cortex bilaterally, right anterior prefrontal cortex, inferior frontal cortex bilaterally, especially on the right, orbital part of inferior frontal gyrus bilaterally, left dorsal anterior cingulate cortex, right primary and secondary visual cortex, and with bilateral anterior and dorsolateral prefrontal cortex, inferior frontal cortex and orbital part of inferior frontal gyrus, bilaterally, bilateral anterior -ventral and dorsal- cingulate cortex, left posterior ventral cingulate cortex, right inferior, middle and anterior temporal gyri, entorhinal and parahippocampal cortex in FTD.. Significant overlapping of apathy perfusion correlates between AD and FTD is seen in frontal areas and anterior cingulate. Right occipital cortex is also involved in AD, while right temporal cortex and left posterior cingulate are involved in FTD. Nuclear imaging could be a useful biomarker for revealing apathy underlying mechanisms, resulting in directed treatments.KEYPOINTSUnderlying neural networks and clinical manifestation of apathy may differ between AD and FTD.Apathy in AD is correlated with hypoperfusion in bilateral frontal areas, more prominent on the right, left anterior cingulate and right occipital cortex.Apathy in FTD is correlated with hypoperfusion in bilateral frontal areas, bilateral anterior cingulate, left posterior cingulate and right temporal cortex.Brain perfusion SPECT with automated BAs analysis and comparison with normal healthy subjects may provide significant information for apathy mechanisms in neurodegenerative disorders, affecting patients' treatment.

Topics: Alzheimer Disease; Apathy; Frontotemporal Dementia; Humans; Perfusion; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Neuropsychiatric symptoms (NPSs) are common in dementia. Their evaluation is based on Neuropsychiatric Inventory (NPI). Neuroimaging studies have tried to elucidate the underlying neural circuits either in isolated NPSs or in specific forms of dementia.. The objective of this study is to evaluate the correlation of NPS in the NPI with Brodmann areas (BAs) perfusion, for revealing BAs involved in the pathogenesis of NPSs in dementia of various etiologies.. We studied 201 patients (82 with Alzheimer's disease, 75 with Frontotemporal dementia, 27 with Corticobasal Syndrome, 17 with Parkinson Disease/Lewy Body Dementia). Exploratory factor analysis was carried out to evaluate underlying groups of BAs, and Principal Component analysis was chosen as extraction method using Varimax rotation. Partial correlation coefficients were computed to explore the association of factors obtained from analysis and NPI items controlling for age, educational yeas, and ACE-R.. We found 6 BAs Factors(F); F1 (BAs 8,9,10,11,24,32,44,45,46,47, bilaterally), F2 (BAs 4,5,6,7,23,31, bilaterally), F3 (BAs 19,21,22,37,39,40, bilaterally), F4 (BAs 20,28,36,38, bilaterally), F5 (BAs 25, bilaterally) and F6 (BAs 17,18, bilaterally). Significant and negative correlation was found between NPI1 (delusions) and F3,F6, NPI2 (hallucinations) and F6, NPI7 (apathy) and F1,F4,F5, NPI3 (agitation) - NPI10 (aberrant motor behavior) - NPI12 (eating disorders) and F1. We did not find any significant correlation for NPI4,5,6,8,9,11 (depression, anxiety, euphoria, disinhibition, irritability, sleep disorders, respectively).. Several NPSs share the same BAs among different types of dementia, while the manifestation of the rest may be attributed to different neural networks. These findings may have an impact on patients' treatment.

Topics: Alzheimer Disease; Cerebral Cortex; Humans; Neuropsychological Tests; Perfusion; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Eating disorders (ED) in dementia represent a significant impairment affecting patients' and caregivers' lives. In frontotemporal dementia (FTD), ED include overeating, sweet food preference, stereotypical eating, and hyperorality, while in Alzheimer's disease (AD), anorexia and appetite loss are the most common ED.. The aim of our study was to highlight Brodmann areas (BAs) implicated specifically in the appearance of ED in FTD and AD.. We studied 141 patients, 75 with FTD and 66 with AD. We used the NeuroGamTM software on the reconstructed single photon emission computed tomography-SPECT data for the automated comparison of BAs perfusion on the left (L) and right (R) hemisphere with perfusion in corresponding BAs of a normal database.. The FTD group included 27 men and 48 women, age (mean±SD) 65.8±8.5 years, duration of disease 3.4±3.3 years, Mini-Mental State Examination (MMSE) 17.9±8.6, ED score on Neuropsychiatric Inventory (NPI) 4.7±8.5. ED in FTD were correlated with hypoperfusion in right anterior and dorsolateral prefrontal cortices (BAs 10R, 46R), left orbitofrontal cortex (BA 12L), orbital part of the right inferior frontal gyrus (BA 47R), and left parahippocampal gyrus (BA 36L). The AD group included 21 men and 45 women, age (mean±SD) 70.2±8.0 years, duration of disease 3.3±2.4 years, MMSE 20.2±6, ED-NPI score 2.7±3.9. ED in AD were correlated with hypoperfusion in left inferior temporal cortex (BA 20L).. SPECT imaging with automated mapping of brain cortex could contribute to the understanding of the neural networks involved in the manifestation of ED in dementia.

Topics: Aged; Alzheimer Disease; Brain Mapping; Cerebral Cortex; Feeding and Eating Disorders; Female; Frontotemporal Dementia; Humans; Male; Middle Aged; Perfusion Imaging; Radiopharmaceuticals; Regression Analysis; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Imaging such as Tc99m-HMPAO single photon emission computed tomography (SPECT), and positron emission tomography/ computed tomography (PET/CT) amyloid scans are used to aid the diagnosis of Alzheimer's disease (AD).. We aimed to correlate the ability of these modalities to differentiate Probable AD and Possible AD using the clinical diagnosis as a gold standard. We also investigated the correlation of severity of amyloid deposit in the brain with the diagnosis of AD.. A retrospective study of 47 subjects (17 Probable AD and 30 Possible AD) who were referred for PET/CT amyloid scans to our centre was conducted. Hypoperfusion in the temporo-parietal lobes on Tc99m-HMPAO SPECT and loss of grey-white matter contrast in cortical regions on PET/CT Amyloid scans indicating the presence of amyloid β deposit were qualitatively interpreted as positive for AD. SPECT and PET/CT were also read in combination (Combo reading). The severity of amyloid β deposit was semiquantitatively assessed in a visual binary method using a scale of Grade 0-4. The severity of amyloid β deposit was assessed in a visual binary method and a semi-quantitative method using a scale of Grade 0-4.. There was significant correlation of Tc99m-HMPAO SPECT, PET/CT amyloid findings and Combo reading with AD. The sensitivity, specificity, PPV and NPV were 87.5%, 73.7%, 58.3% and 93.3% (SPECT); 62.5%, 77.4%, 58.8% and 80.0% (PET/CT) and 87.5%, 84.2%, 70.0% and 30.0% (Combo reading) respectively. The grade of amyloid deposition was not significantly correlated with AD (Spearman's correlation, p=0.687).. There is an incremental benefit in utilizing PET/CT amyloid imaging in cases with atypical presentation and indeterminate findings on conventional imaging of Alzheimer's disease.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Brain; Female; Humans; Male; Middle Aged; Neuroimaging; Positron-Emission Tomography; Retrospective Studies; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Alzheimer's disease (AD) is characterized by widespread degeneration of cholinergic neurons, particularly in the basal forebrain. However, the pattern of these deficits and relationship with known brain networks is unknown. In this study, we sought to clarify this and used

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Azetidines; Cerebrovascular Circulation; Female; Humans; Male; Prosencephalon; Pyridines; Radiopharmaceuticals; Receptors, Nicotinic; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Patients with early-onset dementia (EOD) often present atypically, making an accurate diagnosis difficult. Single-photon emission-computed tomography (SPECT) provides an indirect measure of cerebral metabolic activity and can help to differentiate between dementia subtypes. This study aims to investigate the clinical utility of SPECT imaging in the diagnosis of early-onset Alzheimer's disease.. All patients attending a tertiary referral clinic specialising in EOD between April 2012 and October 2013 were included in the study. Statistical analysis of SPECT patterns with clinical diagnoses, Addenbrooke's Cognitive Examination version 3 scores, and magnetic resonance imaging (MRI) atrophy was undertaken.. The results demonstrated a highly significant association between SPECT hypoperfusion patterns and clinical diagnoses. SPECT changes were demonstrated more frequently than MRI atrophy.. The results suggest that SPECT imaging may be a useful adjunct to clinical evaluation and a more sensitive biomarker than standard structural imaging.

Topics: Aged; Alzheimer Disease; Atrophy; Brain; Cognition; Dementia; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Radiopharmaceuticals; Retrospective Studies; Technetium Tc 99m Exametazime; Tertiary Care Centers; Tomography, Emission-Computed, Single-Photon

Early diagnosis of Alzheimer's disease (AD) based on clinical criteria alone may be problematic, while current and future treatments should be administered earlier in order to be more effective. Thus, various disease biomarkers could be used for early detection of AD. We evaluated brain perfusion with 99mTc-HMPAO single photon emission computed tomography (SPECT) and Brodmann areas (BAs) mapping in mild AD using an automated software (NeuroGam) for the semi-quantitative evaluation of perfusion in BAs and the comparison with the software's normal database. We studied 34 consecutive patients with mild AD: 9 men, 25 women, mean age 70.9 ± 8.1 years, mean Mini-Mental State Examination 22.6 ± 2.5. BAs 25L, 25R, 38L, 38R, 28L, 28R, 36L, and 36R had the lower mean perfusion values, while BAs 31L, 31R, 19R, 18L, 18R, 17L, and 17R had the higher mean values. Compared with healthy subjects of the same age, perfusion values in BAs 25L, 25R, 28R, 28L, 36L, and 36R had the greatest deviations from the healthy sample, while the lowest deviations were found in BAs 32L, 32R, 19R, 24L, 17L, 17R, 18L, and 18R. A percentage of ≥94% of patients had perfusion values more than -2SDs below the mean of healthy subjects in BAs 38R, 38L, 36L, 36R, 23L, 23R, 22L, 44L, 28L, 28R, 25L, and 25R. The corresponding proportion was less than 38% for BAs 11L, 19R, 32L, 32R, 18L, 18R, 24L, and 17R. In conclusion, brain SPECT studies with automated perfusion mapping could be useful as an ancillary tool in daily practice, revealing perfusion impairments in early AD.

Topics: Aged; Alzheimer Disease; Brain; Brain Mapping; Early Diagnosis; Female; Humans; Male; Mental Status Schedule; Neuropsychological Tests; Pattern Recognition, Automated; Radiopharmaceuticals; Software; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Brain imaging with glucose ((18)F-FDG) PET or blood flow (hexamethylpropyleneamine oxime) SPECT is widely used for the differential diagnosis of dementia, though direct comparisons to clearly establish superiority of one method have not been undertaken.. Subjects with Alzheimer disease (AD; n = 38) and dementia with Lewy bodies (DLB; n = 30) and controls (n = 30) underwent (18)F-FDG PET and SPECT in balanced order. The main outcome measure was area under the curve (AUC) of receiver-operating-characteristic analysis of visual scan rating.. Consensus diagnosis with (18)F-FDG PET was superior to SPECT for both dementia vs. no-dementia (AUC = 0.93 vs. 0.72, P = 0.001) and AD vs. DLB (AUC = 0.80 vs. 0.58, P = 0.005) comparisons. The sensitivity and specificity for dementia/no-dementia was 85% and 90%, respectively, for (18)F-FDG PET and 71% and 70%, respectively, for SPECT.. (18)F-FDG PET was significantly superior to blood flow SPECT. We recommend (18)F-FDG PET be performed instead of perfusion SPECT for the differential diagnosis of degenerative dementia if functional imaging is indicated.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Female; Fluorodeoxyglucose F18; Humans; Lewy Body Disease; Male; Neuropsychological Tests; Perfusion; Positron-Emission Tomography; Prospective Studies; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

A consensus on the brain dysfunction(s) underlying the delusions of Alzheimer's Dementia (AD) remains to be achieved. The aim of the present study was to test the hypothesis that content-based categorization of delusional ideas manifests as dysfunction of category-specific brain regions.. Fifty-nine consecutive first-visit AD outpatients underwent Single Photon Emission Computed Tomography (SPECT), Mini-Mental State Examination, and Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity scale (BEHAVE-AD-FW) to assess cerebral blood flow (CBF), cognitive function, and delusion, respectively. SPECT images were analyzed by SPM5.. CBF decreased at the temporal poles and right inferior temporal gyrus in "delusion of theft," at the temporal poles in "suspiciousness/paranoia," at the right parahippocampal gyrus and insula in "abandonment," and at the right amygdala in "Residence is not home.". Our findings offer a perspective on the discrete categories of the pathological thoughts of AD patients that have previously been lumped together as "delusions." Dysfunction of the temporal poles may be associated with a socioemotional deterioration that may include pathological suspiciousness. Delusion of theft may be a manifestation of socioemotional deterioration and poor insight. Emotional factors may be essential for delusions of abandonment and "not home."

Topics: Aged; Alzheimer Disease; Brain Diseases; Cerebrovascular Circulation; Cognition; Cross-Sectional Studies; Delusions; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Neuropsychological Tests; Radiopharmaceuticals; Severity of Illness Index; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most common types of dementia in the presenile population. Episodic memory impairment, the clinical hallmark of AD, can also be encountered in patients with FTD, complicating accurate diagnosis. Several studies in FTD have correlated memory deficits with neuroimaging findings, but lacked to compare neuroimaging results in FTD patients with and without memory impairment, while this latter analysis may give us insight into the underlying mechanisms of memory impairment in FTD. The aim of the present study was to compare (99m)Tc-HMPAO SPECT hypoperfusion patterns between FTD with episodic memory impairment (n = 13), FTD patients without episodic memory impairment (n = 10) as well as early onset (< 70 yrs) AD patients (n = 13), and controls (n = 15). We performed our analyses by means of Statistical Parametric Mapping software (SPM5), and showed that FTD patients with episodic memory impairment had lower perfusion in the right temporal lobe compared with FTD patients without memory impairment. Lower perfusion in this region correlated with worse memory performance on the Clinical Dementia Rating scale in FTD patients. With equal performances on memory tests, patients with early onset AD showed posterior temporal and parietal lobe hypoperfusion in comparison with patients with FTD and memory impairment, while vice versa hypoperfusion in the anterior frontotemporal regions was found in FTD patients with memory impairment in comparison with AD.

Topics: Alzheimer Disease; Female; Frontotemporal Dementia; Humans; Male; Memory Disorders; Memory, Episodic; Middle Aged; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To demonstrate the utility of semi-quantitative circumferential-profile analysis of regional cerebral blood flow (rCBF) SPECT in Alzheimer's disease (AD) versus white matter vascular dementia (WM-VaD).. Subjects underwent dementia evaluation, MRI and Tc-99m HMPAO SPECT. rCBF patterns from 11 AD and 20 WM-VaD patients were compared to 17 controls using semi-quantitative circumferential-profile analysis.. AD patients showed more significant semi-quantitative circumferential-profile reductions in the posterior temporo-parietal regions, whereas WM-VaD patients demonstrated greater reductions involving the frontal regions of the brain.. Semi-quantitative circumferential-profile analysis provides a practical semi-quantitative method to evaluate brain SPECT scans in AD versus WM-VaD patients.

Topics: Aged; Alzheimer Disease; Case-Control Studies; Cerebrovascular Circulation; Dementia, Vascular; Female; Humans; Image Processing, Computer-Assisted; Linear Models; Magnetic Resonance Imaging; Male; Radiopharmaceuticals; Retrospective Studies; Statistics, Nonparametric; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Corticobasal syndrome (CBS) has a heterogeneous neuropathological spectrum, ranging from the classical corticobasal degeneration to Alzheimer's disease (AD). The neuropathology of CBS is still unpredictable. CSF tau/abeta ratio is a reliable marker of AD.. To evaluate the presence of a distinct clinical and neuroimaging CBS phenotype according to CSF pattern.. 30 patients fulfilling current clinical criteria for CBS entered the study. Each patient underwent a clinical and standardised neuropsychological assessment, and CSF analysis (total tau and abeta42 dosages). CSF AD-like pattern and CSF non-AD like pattern (nAD-like) were identified. In 23 CBS cases, (99m)Tc-ECD single photon emission computed tomography (SPECT) scan was performed and analysed by statistical parametric mapping.. CSF AD-like pattern was reported in six cases (20%). The two subgroups did not differ in demographic characteristics or global cognitive impairment. The AD-like group showed greater impairment of memory performances, language and psychomotor speed while the nAD-like group had more severe extrapyramidal syndrome with comparable apraxia scores. Voxel by voxel analysis on SPECT images demonstrated that CBS AD-like patients had greater hypoperfusion in the brain areas typically affected by AD-namely, precuneus, posterior cingulate and hippocampus, bilaterally-compared with nAD-like patients (p<0.001). No clusters above the pre-established threshold were detected when nAD-like were compared with AD-like patients.. CSF AD-like profile in CBS is associated with earlier memory impairment and brain abnormalities typically found in classical AD. These findings argue for the usefulness of CSF testing to identify AD in CBS, and might suggest a different pharmacological approach on the basis of biological data.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Basal Ganglia; Biomarkers; Cerebral Cortex; Female; Humans; Male; Middle Aged; Neurodegenerative Diseases; Neuropsychological Tests; Peptide Fragments; Predictive Value of Tests; Syndrome; tau Proteins; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Patients with Alzheimer's disease (AD) display a multiplicity of cognitive deficits in domains such as memory, language, and attention, all of which can be clearly linked to the underlying neuropathological alterations. The typical degenerative changes occur early on in the disease in the temporal-parietal lobes, with other brain regions, such as the frontal cortex, becoming more affected as the disease progresses. In light of the importance of the parietal cortex in mediating visuospatial attentional processing, in the present study, we investigated a deficit in covert orienting of visual attention and its relationship to cortical hypoperfusion in AD. We characterized the visual attentional profile of 21 AD patients, relative to that of 26 matched normal individuals, and then assessed the correspondence between behavior and hypoperfusion, as measured by regional cerebral blood flow using SPECT. Relative to controls, the AD group demonstrated a unilateral attentional deficit, with disproportionate slowing in reorienting attention to targets in the left compared to the right hemispace, especially following an invalid peripheral cue. Furthermore, even in the presence of bilateral pathology typical of AD, there was a positive correlation between this unilateral attentional disorder and the magnitude of the right superior parietal lobe hypoperfusion. The association of the altered attentional processing profile (i.e., greater difficulty disengaging attention from right-sided stimuli) with right-hemisphere-predominant hypoperfusion not only confirms the critical role of the right parietal lobe in covert attentional orienting but, more importantly, identifies a potential locus of the behavioral alterations in visuospatial processing in AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Analysis of Variance; Attention; Cerebral Cortex; Cerebrovascular Circulation; Cues; Educational Status; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Neuropsychological Tests; Parietal Lobe; Photic Stimulation; Psychomotor Performance; Radiopharmaceuticals; Reaction Time; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Visual Perception

Aberrant motor behaviour (AMB) in Alzheimer's disease shares behavioural correlates with obsessive compulsive disorder (OCD). We investigated whether AMB was also comparable in terms of metabolic activity in the orbitofrontal cortex (OFC), an area shown to be hyperactive in OCD. In this study 135 patients meeting research criteria for Alzheimer's disease were identified from a database of patients recruited as part of a phase II drug trial. These patients were assessed using the Neuropsychiatric Inventory, the Alzheimer's disease assessment scale, cognitive subscale and perfusion SPECT performed with 99Tc(m) hexamethylpropyleneamine oxime. Regions of interest were created for orbitofrontal cortices and basal ganglia. In 35 patients with AMB, adjusted tracer uptake was greater in the OFC. This reached statistical significance in right superior, left superior, right medial and left medial orbital gyri (p < 0.05). The association between AMB and hyperactivity in the OFC remained significant after adjusting for the presence of anxiety. These results parallel the OFC hypermetabolism consistently seen in OCD. One model of OCD, proposes that dysfunctional interactions between frontal regions, including the OFC, produce the characteristic symptoms of OCD. The behaviour is though to be brought about by a perceived incompleteness of performing a task and is caused by an error in normal reward signals initiated upon task completion. These finding indicate that AMB in Alzheimer's disease are brought about by the same mechanistic failure.

Topics: Aged; Alzheimer Disease; Basal Ganglia; Cerebrovascular Circulation; Clinical Trials, Phase II as Topic; Female; Frontal Lobe; Humans; Male; Motor Activity; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

(99m)Tc-exametazime single photon emission computed tomography (SPECT) scans of 36 patients with Alzheimer's disease (AD) and 30 with dementia with Lewy bodies (DLB) underwent region of interest (ROI) and principal component analysis (PCA). Principal component analysis was performed on the entire ROI data set. Principal components (PCs) were obtained, representing common intercorrelated regions in AD and DLB. Topographic expression that signified the extent to which a participant expressed the topographic covariance pattern was derived and used as a discriminatory variable. Principal components were identified, accounting for 77% of total data variance. Significant (PC x group) interaction was observed (P < .001). Topographic expression was significantly higher in DLB than AD (F(1,64) = 21.6, P < .001), and differentiated DLB from AD with sensitivity 73% specificity 72%. Calculating the topographic expression in an independent data set of 48 patients with AD and 23 with DLB gave sensitivity = 70%, specificity = 67%. Principal component analysis captures additional sources of variance and if perfusion SPECT is the only scan available, this procedure may offer extra information.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Analysis of Variance; Brain; Cerebrovascular Circulation; Dementia; Diagnosis, Differential; Female; Humans; Lewy Body Disease; Male; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The diagnosis of Alzheimer disease (AD) at an early age of onset may be a challenging task. The diagnosis of such a type of dementia may be even more difficult when concomitant depressive symptoms occur. We report the case of a 51-year-old woman who was admitted at a Psychiatric Day Hospital presenting with depressive symptoms, visuospatial deficits, apraxia, and minor memory loss. The patient underwent long-term antidepressant therapy, but despite the improvement of depressive symptoms, there was progressive cognitive deterioration. Otherwise, the prior clinical history was unremarkable, and there was no family history of dementia. The clinical examination revealed cognitive deficits in several domains. The patient scored 12 in the Mini-Mental State Examination. Routine laboratory tests were normal. Magnetic resonance (MR) imaging showed global brain volume loss more pronounced than would be expected for someone of the patient's age, especially in the precuneus-a pattern of posterior cortical atrophy consistent with the diagnosis of early-onset AD. Images obtained with 99mTc-HMPAO single-photon emission computed tomography (SPECT) also revealed marked brain hypoperfusion involving the left parietal lobe, far beyond the regions of brain volume loss. This clinical case report illustrates the relative contribution of both MR imaging and SPECT for the diagnosis of dementia in a patient with concomitant depressive symptoms. Apart from contributing to the diagnosis of dementia beyond the traditional exclusionary approach, neuroimaging is increasingly being used to classify its particular subtypes. The role of neuroimaging role in AD is also supported by a recent proposal of revised diagnostic criteria, which take into account abnormal biomarkers of disease.

Topics: Alzheimer Disease; Brain; Cognition Disorders; Female; Humans; Magnetic Resonance Imaging; Mental Status Schedule; Middle Aged; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Repetitive questioning is among the most common and burdensome of the behavioral and psychological symptoms of Alzheimer's disease (AD). Regardless of the clinical significance of the repetitive questioning, the neural substrates involved remain unclear. Fifty-eight consecutive patients with AD participated in this study. The score of repetitive questioning behavior was evaluated by multiplying the severity by the frequency of the behavior. They underwent brain SPECT with (99m)Tc-ethylcysteinate dimer. Scores of repetitive questioning behavior had a significant positive correlation with regional cerebral blood flow (rCBF) in the bilateral pericallosal regions. After removing the effect of memory test scores, we found a significant positive correlation of scores of repetitive questioning behavior to rCBF in the left pericallosal region. The pericallosal region includes the upper precuneus, cingulate, and posterior cingulate cortices on 3DSRT. Repetitive questioning behavior among AD patients might be a manifestation of mental state associated with a relative increase or preservation of rCBF in the left pericallosal region.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain Mapping; Cerebral Cortex; Female; Functional Laterality; Humans; Imaging, Three-Dimensional; Impulsive Behavior; Male; Mental Status Schedule; Middle Aged; Psychiatric Status Rating Scales; Regional Blood Flow; Statistics, Nonparametric; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The aim of this article is to compare patients with Alzheimer's disease (AD) pathology and corticobasal degeneration pathology (CBD) presenting as corticobasal syndrome (CBS). Clinicopathologic series was used. Five patients with AD and 11 patients with CBD were clinically diagnosed with CBS. Patients with AD pathology had an earlier age of onset than patients with CBD pathology (58 vs. 68 years, P = 0.004), but the two groups had similar disease duration and core features of CBS. Tremors were only present in CBD cases (73%, P = 0.026), but myoclonus was more common in AD than CBD (80 vs. 18%, P = 0.036). Neuropsychological testing showed similar degrees of memory impairment and attentional deficits. (99m)Tc-HMPAO SPECT imaging demonstrated parietal hypoperfusion in AD patients and frontotemporal hypoperfusion in CBD patients. AD patients with clinical CBS have similar characteristics to CBD patients. Functional brain imaging may have greater utility than the clinical and neuropsychological features in differentiating AD presenting as CBS from CBD.

Topics: Aged; Alzheimer Disease; Autopsy; Basal Ganglia; Cerebral Cortex; Female; Humans; Male; Memory Disorders; Middle Aged; Neurodegenerative Diseases; Neuropsychological Tests; Retrospective Studies; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Principal component analysis (PCA) provides a method to explore functional brain connectivity. The aim of this study was to identify regional cerebral blood flow (rCBF) distribution differences between Alzheimer's disease (AD) patients and controls (CTR) by means of volume of interest (VOI) analysis and PCA. Thirty-seven CTR, 30 mild AD (mildAD) and 27 moderate AD (modAD) subjects were investigated using single photon emission computed tomography with (99m)Tc-hexamethylpropylene amine oxime. Analysis of covariance (ANCOVA), PCA, and discriminant analysis (DA) were performed on 54 VOIs. VOI analysis identified in both mildAD and modAD subjects a decreased rCBF in six regions. PCA in mildAD subjects identified four principal components (PCs) in which the correlated VOIs showed a decreased level of rCBF, including regions that are typically affected early in the disease. In five PCs, including parietal-temporal-limbic cortex, and hippocampus, a significantly lower rCBF in correlated VOIs was found in modAD subjects. DA significantly discriminated the groups. The percentage of subjects correctly classified was 95, 70, and 81 for CTR, mildAD and modAD groups, respectively. PCA highlighted, in mildAD and modAD, relationships not evident when brain regions are considered as independent of each other, and it was effective in discriminating groups. These findings may allow neurophysiological inferences to be drawn regarding brain functional connectivity in AD that might not be possible with univariate analysis.

Topics: Aged; Alzheimer Disease; Analysis of Variance; Brain; Brain Mapping; Cerebrovascular Circulation; Discriminant Analysis; Female; Hippocampus; Humans; Male; Middle Aged; Parietal Lobe; Principal Component Analysis; Radiopharmaceuticals; Severity of Illness Index; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

This study examined the influence of linearization correction (LC) on brain perfusion single-photon emission computed tomography (SPECT) for the diagnosis of Alzheimer's disease (AD).. The early onset group (<65 years old) consisted of 10 patients with AD, and the late onset group (>/=65 years old) of 13 patients with AD. Age-matched controls included seven younger and seven older normal volunteers. Tc-99m hexamethyl propyleneamine oxine (HMPAO) SPECT images were reconstructed with or without LC [LC (+) or LC (-)] and a statistical analysis was performed using a three-dimensional stereotactic surface projection (3D-SSP). In addition, a fully automatic diagnostic system was developed, which calculated the proportion of the number of abnormal pixels in the superior and inferior parietal lobule, as well as in the precuneus and posterior cingulate gyrus.. The areas under the receiver-operating characteristic curve (AUCs) of the early onset group for conventional axial SPECT images, SPECT + 3D-SSP images and the fully automatic diagnostic system were 0.71, 0.88, and 0.92 in LC (-) and 0.67, 0.85, and 0.91 in LC (+), respectively. The AUCs of the late onset group were 0.50, 0.61, and 0.79 in LC (-) and 0.49, 0.67, and 0.85 in LC (+), respectively.. LC on Tc-99m HMPAO SPECT did not significantly influence the diagnostic performance for differentiating between AD and normal controls in either early or late onset AD. Further examination with individuals suffering from very mild dementia is, therefore, expected to elucidate the effect of LC on minimally hypoperfused areas.

Topics: Age of Onset; Aged; Alzheimer Disease; Case-Control Studies; Cerebrovascular Circulation; Female; Humans; Imaging, Three-Dimensional; Linear Models; Male; Middle Aged; Retrospective Studies; ROC Curve; Stereotaxic Techniques; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The aim of this study is to investigate the diagnostic value of perfusion 99mTc-exametazime single photon emission computed tomography (SPECT) in the diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) in comparison with dopaminergic 123I-2beta-carbomethoxy-3beta-(4-iodophenyl)-n-(3-fluoropropyl) nortropane (FP-CIT) SPECT imaging.. Subjects underwent 99mTc-exametazime scanning (39 controls, 36 AD, 30 DLB) and 123I-FP-CIT scanning (33 controls, 33 AD, 28 DLB). For each scan, five raters performed visual assessments blind to clinical diagnosis on selected transverse 99mTc-exametazime images in standard stereotactic space. Diagnostic accuracy of 99mTc-exametazime was compared to 123I-FP-CIT results for the clinically relevant subgroups AD and DLB using receiver operating characteristic (ROC) curve analysis.. Inter-rater agreement for categorizing uptake was "moderate" (mean kappa = 0.53) for 99mTc-exametazime and "excellent" (mean kappa = 0.88) for 123I-FP-CIT. For AD and DLB, consensus rating matched clinical diagnosis in 56% of cases using 99mTc-exametazime and 84% using 123I-FP-CIT. In distinguishing AD from DLB, ROC analysis revealed superior diagnostic accuracy with 123I-FP-CIT (ROC curve area 0.83, sensitivity 78.6%, specificity 87.9%) compared to occipital 99mTc-exametazime (ROC curve area 0.64, sensitivity 64.3%, specificity 63.6%) p = 0.03.. Diagnostic accuracy was superior with 123I-FP-CIT compared to 99mTc-exametazime in the differentiation of DLB from AD.

Topics: Aged; Alzheimer Disease; Control Groups; Diagnosis, Differential; Dopamine; Female; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Neurofibrillary Tangles; Occipital Lobe; Regional Blood Flow; ROC Curve; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon; Tropanes

The Development of Screening Guidelines and Clinical Criteria of Predementia Alzheimer's Disease (DESCRIPA) multicenter study enrolled patients with MCI or subjective cognitive complaints (SUBJ), a part of whom underwent optional brain perfusion SPECT. These patients were classified as SUBJ (n = 23), nonamnestic MCI (naMCI; n = 17) and amnestic MCI (aMCI; n = 40) based on neuropsychology. Twenty healthy subjects formed the control (CTR) group. Volumetric regions of interest (VROI) analysis was performed in six associative cortical areas in each hemisphere. ANOVA for repeated measures, corrected for age and center, showed significant differences between groups (p = 0.01) and VROI (p < 0.0001) with a significant group-region interaction (p = 0.029). In the post hoc comparison, SUBJ did not differ from CTR. aMCI disclosed reduced uptake in the left hippocampus and bilateral temporal cortex (compared with CTR) or in the left hippocampus and bilateral parietal cortex (compared with SUBJ). In the naMCI group, reduced VROI values were found in the bilateral temporal cortex and right frontal cortex. In the comparison between aMCI and naMCI, the former had lower values in the left parietal cortex and precuneus. Discriminant analysis between SUBJ/CTR versus all MCI patients allowed correct allocations in 73 % of cases. Mean VROI values were highly correlated (p < 0.0001) with the learning measure of a verbal memory test, especially in the bilateral precunei and parietal cortex and in the left hippocampus. In a subset of 70 patients, mean VROI values showed a significant correlation (p < 0.05) with the white matter hyperintensities score on MRI. In conclusion, MCI subtypes have different perfusion patterns. The aMCI group exhibited a pattern that is typical of early Alzheimer's disease, while the naMCI group showed a more anterior pattern of hypoperfusion. Instead, a homogeneous group effect was lacking in SUBJ.

Topics: Aged; Alzheimer Disease; Amnesia; Analysis of Variance; Attention; Brain; Cerebral Cortex; Cerebrovascular Circulation; Cognition; Cognition Disorders; Female; Frontal Lobe; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Neuropsychological Tests; Severity of Illness Index; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon; Verbal Learning

Statistical parametric mapping (SPM) is used worldwide to compare brain perfusion single photon emission computed tomography (SPECT) data. The default template within the SPM package used for SPECT image normalization includes images of a group of healthy subjects studied with [(99m)Tc]HMPAO. Since [(99m)Tc]HMPAO and [(99m)Tc]ECD have shown to distribute differently in SPECT studies, we formulated the hypothesis that comparing set of [(99m)Tc]ECD data normalized by means of a [(99m)Tc]HMPAO template may lead to incorrect results.. A customized [(99m)Tc]ECD template was built with SPECT and magnetic resonance imaging (MRI) images of 22 neurologically healthy women. Then, two sets of subjects, i.e. a group of patients with very early Alzheimer's disease (eAD) and a matched control group, studied by means of [(99m)Tc]ECD SPECT, were chosen for comparisons. The same statistical approach (t-test between eAD patients and controls and correlation analysis between brain SPECT and a cognitive score) was applied twice, i.e. after normalization with either the default [(99m)Tc]HMPAO template or the customized [(99m)Tc]ECD template.. In the comparison between eAD and controls, a cluster of difference in the posterior cingulate gyrus of both hemispheres was only highlighted when using the customized [(99m)Tc]ECD template, but was missed when using the default [(99m)Tc]HMPAO template. In the correlation between brain perfusion and a cognitive score, the significant cluster was more significant and far more extended, also including the right superior temporal gyrus, using the customized [(99m)Tc]ECD template than using the default [(99m)Tc]HMPAO template.. These data suggest the need of customized, radiopharmaceutical-matched SPECT templates to be used within the SPM package. The present customized [(99m)Tc]ECD template is now freely available on the web.

Topics: Adolescent; Adult; Aged, 80 and over; Alzheimer Disease; Brain; Brain Mapping; Cysteine; Female; Gyrus Cinguli; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Spatial smoothing performed after spatial normalization on the easy Z-score Imaging System (eZIS) is considered to affect signal size. The purpose of this study was to analyze quantitatively the influence of the smoothing process on eZIS using the voxel of interest (VOI) method. A normal database (NDB) was established using (99m)Tc-Hexamethylpropyleneamine oxime (HMPAO) brain perfusion SPECT images of thirty healthy volunteers. Then the NDB was smoothed with various Gaussian kernels (2, 4, 8, 12, 16 mm). Artificial lesions with known volumes and reduction of tracer uptake were made on one of the healthy volunteer images, and eZIS analysis was performed on the NDB of the same Gaussian kernel, respectively. The signal size of small-sized lesions was expanded 5.1 times to the true signal size of a 12 mm Gaussian kernel. On the other hand, the medium lesion size, which was approximately the same size as the posterior cingulate gyrus, was expanded 2.9 times to true signal size. Estimation of the false positive area using the extraction estimation method at lesion size medium indicated the lowest value at 8, 12 mm Gaussian kernel smoothing. The smoothing procedure at 8-12 mm Gaussian kernel is effective to detect a focal abnormality in the brain SPECT of Alzheimer's disease.

Topics: Alzheimer Disease; Brain; Cerebrovascular Circulation; Humans; Image Processing, Computer-Assisted; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To relate cerebral perfusion abnormalities to subsequent changes in clinical status among patients with mild cognitive impairment (MCI).. Perfusion single photon emission computed tomography (SPECT) images were acquired in 105 elderly patients without dementia with MCI, using 99mTc-HMPAO. Clinical outcome after a 5-year follow-up period was heterogeneous.. Baseline SPECT data differed in those patients with MCI who were later diagnosed with Alzheimer's disease (the converter group) from those patients with MCI who experienced clinically evident decline but did not progress to a diagnosis of Alzheimer's disease within the follow-up period (the decliner group), from patients with MCI who had no clinical evidence of progression (the stable group), and from a group of 19 normal subjects (the control group). The most consistent decreases in relative perfusion in converters compared with the normal, stable and decliner groups were observed in the caudal anterior cingulate, and in the posterior cingulate. In addition, converters showed increased relative perfusion in the rostral anterior cingulate in comparison to the stable and decliner groups. A group of patients with Alzheimer's disease were also included for purposes of comparison. The group of patients with Alzheimer's disease at baseline differed from each of the other groups, with temporoparietal regions showing the most significant reductions in perfusion.. These results suggest that clinical heterogeneity in MCI is reflected in SPECT perfusion differences, and that the pattern of perfusion abnormalities evolves with increasing clinical severity.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Cognition Disorders; Disease Progression; Female; Follow-Up Studies; Humans; Male; Mental Status Schedule; Radiopharmaceuticals; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Loss of the alpha4beta2 nicotinic receptor subtype is found at autopsy in Alzheimer's disease.. To investigate in vivo changes in this receptor using single-photon-emission CT (SPECT) with 123I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380), a novel nicotinic acetylcholine receptor ligand which binds predominantly to the alpha4beta2 receptor.. 32 non-smoking subjects (16 with Alzheimer's disease and 16 normal elderly controls) underwent 123I-5IA-85380 and perfusion (99mTc-hexamethylenepropyleneamine oxime (HMPAO)) SPECT scanning. Region of interest analysis was performed with cerebellar normalisation.. Significant bilateral reductions in nicotinic receptor binding were identified in frontal (left, p = 0.004; right, p = 0.002), striatal (left, p = 0.004; right, p = 0.003), right medial temporal (p = 0.04) and pons (p<0.001) in patients with AD compared to controls. There were no significant correlations with clinical or cognitive measures. The pattern of nicotinic binding significantly differed from that of perfusion in both patients with AD and controls. Both 123I-5IA-85380 and 99mTc-HMPAO SPECT imaging demonstrated similar diagnostic performance in correctly classifying controls and patients with AD.. Using 123I-5IA-85380 SPECT we found changes consistent with significant reductions in the nicotinic alpha4beta2 receptor in cortical and striatal brain regions. This method could facilitate diagnosis and may be useful for monitoring progression of the disease and response to treatment in patients with AD and related diseases.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Azetidines; Case-Control Studies; Disease Progression; Female; Humans; Male; Pyridines; Receptors, Nicotinic; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the commonest causes of presenile dementia. In the absence of a biological marker, diagnosis is reliant on clinical evaluation. Confirmation is often sought from neuroimaging, including single-photon emission computed tomography (SPECT). Most previous SPECT studies lack pathological validation.. To examine the accuracy of SPECT in differentiating FTD from AD in patients with subsequent pathological confirmation.. Technetium-99-labelled hexamethyl propylene amine oxime SPECT images obtained at initial evaluation in 25 pathologically confirmed cases of FTD were examined. These images were visually rated by an experienced blinded nuclear medicine consultant and compared with those of 31 patients with AD, also with pathological validation.. A reduction in frontal cerebral blood flow (CBF) was more common in FTD and was of diagnostic value (sensitivity 0.8, specificity 0.65 and likelihood ratio (LR) 2.25; 95% CI 1.35 to 3.77). A pattern of bilateral frontal CBF reduction without the presence of associated bilateral parietal CBF change is diagnostically more accurate (sensitivity 0.80, specificity 0.81 and +LR 4.13, 95% CI 1.96 to 8.71). Diagnostic categorisation (FTD or AD) on the basis of SPECT alone was less accurate than clinical diagnosis (based on neurology and detailed neuropsychological evaluation). One patient with FTD was initially clinically misdiagnosed as AD, owing to the lack of availability of full neuropsychological assessment. However, SPECT correctly diagnosed this patient, providing a diagnostic gain of 4%.. Technetium-99-labelled hexamethyl propylene amine oxime SPECT CBF patterns provide valuable information in the diagnosis of FTD and AD. These data can be better used as an adjunct to clinical diagnosis if pathology is to be correctly predicted in life.

Topics: Aged; Alzheimer Disease; Brain; Dementia; Diagnosis, Differential; Female; Frontal Lobe; Humans; Male; Middle Aged; Radiopharmaceuticals; Regional Blood Flow; Retrospective Studies; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

Technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO) and technetium-99m N,N-1,2-ethylene diylbis-Lcysteine diethyl ester dihydrochloride ((99m)Tc-ECD) SPECT are widely used in Dementia Clinics for early and differential diagnosis. They have been shown to perform differently in Alzheimer's disease (AD), but the impact of such differences on both research and clinical work is unknown. We investigated the differences between the 2 compounds in research work by assessing correlation between performance on a verbal memory task and cerebral perfusion in 2 matched groups of AD patients.. Nineteen pairs of patients with mild to moderate AD undergoing SPECT with either 99mTc-HMPAO or (99m)Tc-ECD were retrospectively selected in a Memory Clinic. Patients were matched for sex, age (+/-3 years) and the Mini-Mental State Examination score (+/-2 points) with a case-control procedure, thus obtaining 2 well-matched groups. The score on the Grober-Buschke selective reminding test (SRT) was correlated with SPECT in each group by means of statistical parametric mapping 99 (height threshold: P<0.01).. (99m)Tc-HMPAO SPECT yielded 3 significant correlation clusters involving inferior and middle frontal gyri, para-hippocampal gyrus and putamen in the right hemisphere; the middle and superior temporal gyri, insula and claustrum in the left hemisphere. (99m)Tc-ECD gave a significant cluster of correlation in left postcentral gyrus and inferior parietal lobule.. (99m)Tc-HMPAO SPECT correlation sites seem more consistent than (99m)Tc-ECD ones with the neurophysiological models of verbal memory, as designed both in normal individuals and in pathological conditions. The demonstration of such relevant differences introduces a source of variability among studies performed with either of the 2 compounds, which must be considered when interpreting results.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Cysteine; Female; Humans; Male; Mental Recall; Organotechnetium Compounds; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Verbal Behavior

To evaluate the feasibility of using the Statistical Parametric Mapping (SPM) program for an automated, voxel-by-voxel assessment of regional cerebral blood flow (rCBF) deficits in Alzheimer's disease (AD) subjects relative to age-matched controls studied with a conventional, single-detector SPECT system.. We used a databank of 99mTc-HMPAO images of 19 patients with a diagnosis of probable AD and 15 elderly healthy volunteers; data were acquired using an Orbiter-Siemens single-detector SPECT system. Using SPM, images were transformed spatially, smoothed (12mm), and the data were compared on a voxel-by-voxel basis with t-tests.. There were significant rCBF reductions in AD patients relative to controls involving regions predicted a priori to be affected in AD, namely the left temporal and parietal neocortices, and the right posterior cingulate gyrus (p<0.05, corrected for multiple comparisons).. The location of rCBF reductions in AD subjects in our study is consistent with the deficits detected in previous functional imaging studies of AD using higher-resolution devices. This suggests the potential usefulness of using SPM for the analysis of data acquired with single-detector SPECT systems, despite the limited sensitivity and spatial resolution of such equipment.

Topics: Aged; Alzheimer Disease; Brain Mapping; Case-Control Studies; Cerebrovascular Circulation; Data Interpretation, Statistical; Feasibility Studies; Female; Humans; Male; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Aim of this study was to find cerebral perfusion correlates of conversion to dementia in patients with amnestic MCI.. 17 healthy subjects (age = 69 +/- 3, 9 females), and 23 amnestic MCI patients (age = 70 +/- 6, 10 females) underwent brain MR scan and (99m)Tc ECD SPECT. Conversion to AD was ascertained on average 19 +/- 10 months after baseline: 9 had converted (age = 69 +/- 3, 4 females), and 14 had not (age = 71 +/- 8, 6 females). We processed SPECT images with SPM2 following an optimized protocol and performed a voxel-based statistical analysis comparing amnestic MCI patients converted to AD and non-converted to dementia vs controls. We assessed the effect of gray matter atrophy on the above results with SPM2 using an optimized Voxel-Based Morphometry (VBM) protocol. We compared significant hypoperfusion with significant atrophy on a voxel-byvoxel basis.. In comparison with normal controls, amnestic MCI patients who converted to AD showed hypoperfusion in the right parahippocampal gyrus and left inferior temporal and fusiform gyri,whereas those who did not convert showed hypoperfusion in the retrosplenial cortex, precuneus and occipital gyri, mainly on the left side. We found no overlap between significant atrophy and significant hypoperfusion regions.. Parahippocampal and inferior temporal hypoperfusion in amnestic MCI patients appears as a correlate of conversion to AD; hypoperfusion in the retrosplenial cortex is involved in memory impairment but does not seem the key prognostic indicator of conversion to dementia.

Topics: Aged; Alzheimer Disease; Amnesia; Analysis of Variance; Brain Mapping; Cerebrovascular Circulation; Disease Progression; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The purpose of this study is to determine the value of Tc-99m HMPAO SPECT in the diagnosis of the dementias, with particular reference to Alzheimer disease.. Tc-99m HMPAO was used with a 3-camera scanner to produce 5 sets of sectional images of the brain. Diagnosis was made by a physician blinded to the clinical diagnosis. Results in 49 subjects were ultimately compared with neuropathologic study of the brain at autopsy.. Sensitivity = 86.7% (68.4-95.6%, 95% confidence interval [CI]), specificity = 89.5% (65.5-98.2% CI), positive predictive value = 92.9% (75.0-98.8% CI), negative predictive value = 81% (57.4-93.7% CI), accuracy = 87.8% (74.5-94.9% CI), likelihood ratio = 8.23% (7.09-9.57% CI).. Comparison is made with several other SPECT and PET series with histopathologic correlation. Brain blood flow SPECT is useful in the diagnosis and differential diagnosis of the dementias.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cerebrovascular Circulation; Dementia; Diagnosis, Differential; False Negative Reactions; False Positive Reactions; Female; Humans; Male; Predictive Value of Tests; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Statistical parametric mapping (SPM) was employed to investigate the regional decline in cerebral blood flow (rCBF) as measured by 99mTc-hexamethyl propylene amine oxime (HMPAO) single photon emission computed tomography (SPECT) in mild Alzheimer's disease (AD). However, the role of the post reconstruction image processing on the interpretation of SPM, which detects rCBF pattern, has not been precisely studied. We performed 99mTc-HMPAO SPECT in mild AD patients and analyzed the effect of linearization correction for washout of the tracer on the detectability of abnormal perfusion.. Eleven mild AD (NINCDS-ADRDA, male/female, 5/6; mean+/-SD age, 70.6+/-6.2 years; mean+/-SD mini-mental state examination score, 23.9+/-3.41; clinical dementia rating score, 1) and eleven normal control subjects (male/female, 4/7; mean+/-SD age, 66.8+/-8.4 years) were enrolled in this study. 99mTc-HMPAO SPECT was performed with a four-head rotating gamma camera. We employed linearization uncorrected (LU) and linearization corrected (LC) images for the patients and controls. The pattern of hypoperfusion in mild AD on LU and LC images was detected by SPM99 applying the same image standardization and analytical parameters. A statistical inter image-group analysis (LU vs. LC) was also performed.. Clear differences were observed between the interpretation of SPM with LU and LC images. Significant hypoperfusion in mild AD was found on the LU images in the left posterior cingulate gyrus, right precuneus, left hippocampus, left uncus, and left superior temporal gyrus (cluster level, corrected p < 0.005). With the LC images, significant hypoperfusion in AD was found only in the bilateral posterior cingulate gyrus and left precuneus (cluster level, corrected p < 0.005). A pattern of greater rCBF distribution at the high flow cortices and low flow cortices was observed on LC and LU images, respectively, in the case of both controls and mild AD patients.. Hippocampal hypoperfusion could be detected by means of SPM in the LU images but not in the LC images. The results of SPM may vary in 99mTc-HMPAO SPECT with or without linearization correction, which should be carefully evaluated when interpreting the pattern of rCBF changes in mild Alzheimer's disease.

Topics: Aged; Alzheimer Disease; Brain; Brain Mapping; Case-Control Studies; Cerebrovascular Circulation; Data Interpretation, Statistical; Female; Humans; Male; Middle Aged; Models, Statistical; Radiography; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To prospectively determine if pulsed arterial spin-labeling perfusion magnetic resonance (MR) imaging depicts regional cerebral hypoperfusion in subjects with Alzheimer disease (AD) and mild cognitive impairment (MCI), compared with perfusion in cognitively normal (CN) subjects, that is consistent with results of fluorodeoxyglucose (FDG) positron emission tomography (PET) and hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) studies of similar populations.. Institutional review board approval and informed consent were obtained. Twenty subjects with AD (13 men, seven women; mean age, 72.9 years), 18 with MCI (nine men, nine women; mean age, 73.3 years), and 23 CN subjects (10 men, 13 women; mean age, 72.9 years) underwent arterial spin-labeling and volumetric T1-weighted structural MR imaging. Perfusion images were coregistered to structural images, corrected for partial volume effects (PVEs) with information from the structural image to determine tissue content of perfusion voxels, and normalized to a study-specific template. Analyses of perfusion differences between groups, with and without corrections for PVEs, were performed on a voxel-by-voxel basis with a one-tailed fixed-effects analysis of covariance model adjusted for age. In addition, tests were performed with and without accounting for global perfusion.. The AD group showed significant regional hypoperfusion, compared with the CN group, in the right inferior parietal cortex extending into the bilateral posterior cingulate gyri (P <.001), bilateral superior and middle frontal gyri (P <.001), and left inferior parietal lobe (P=.007). When PVEs from underlying cortical gray matter atrophy were accounted for, the AD group still showed hypoperfusion in the right inferior parietal lobe extending into the bilateral posterior cingulate gyri (P <.001) and left (P=.003) and right (P=.012) middle frontal gyri. With a more liberal voxel-level threshold of P <.01, the MCI group showed significant regional hypoperfusion relative to the CN group in the inferior right parietal lobe (P=.046), similar to the region of greatest significance in the AD group.. Arterial spin-labeling MR imaging showed regional hypoperfusion with AD, in brain regions similar to those seen in FDG PET and HMPAO SPECT studies of similar populations; this hypoperfusion persists after accounting for underlying cortical gray matter atrophy.

Topics: Aged; Alzheimer Disease; Analysis of Variance; Brain; Cerebrovascular Circulation; Cognition Disorders; Female; Humans; Magnetic Resonance Imaging; Male; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Spin Labels; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Topics: Aged; Alzheimer Disease; Blood Flow Velocity; Brain; Cerebrovascular Circulation; Dementia; Diagnosis, Differential; Female; Fractals; Humans; Imaging, Three-Dimensional; Male; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

We investigated whether brain SPECT findings show any differences between patients with mild and moderate Alzheimer's disease (AD) and to compare results with event related potentials (ERPs). Twenty-two patients with mild to moderate AD diagnosed according to NINCDS-ADRDA criteria and 10 age-matched control subjects were included in this prospective study. All subjects underwent ERP recordings and Tc-99m HMPAO brain SPECT study. Cortical perfusion index (CPI) was calculated as the ratio of cortical activity to the cerebellum activity. CPI was found to be statistically lower in bilaterally posterolateral temporal cortex and precuneus in the moderate AD compared to the control group. There was no statistically significant difference between the mild AD and control groups for CPI in any cortical areas. The mean P300 latency was statistically prolonged in the mild and moderate AD compared to the control group. In addition, in moderate AD P300 latency was longer than in mild AD. While the mean P300 amplitude was statistically reduced in moderate AD compared to the control and mild AD, there was no statistically significant difference between the mild AD and control groups. There was a strong negative correlation between P300 latency and CPI in the right and left precuneus in the moderate AD group. The present study suggested that Tc-99m HMPAO SPECT study is the more appropriate technique for patients with moderate AD rather than mild AD. Our results indicated that alterations in ERPs, especially prolongation of P300 latency could be a finding that occurred earlier than the deterioration in cerebral blood flow. We thought that precuneus is closely related to cognitive function and may have an important role in the pathophysiology of AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain Mapping; Case-Control Studies; Cerebral Cortex; Electroencephalography; Evoked Potentials; Female; Functional Laterality; History, Ancient; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Prospective Studies; Radiopharmaceuticals; Reaction Time; Statistics, Nonparametric; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To assess the role of 99mTc-hexamethylpropyleneamine oxime single-photon emission computed tomography (99mTc-HMPAO SPECT) imaging of the precuneus and medial temporal lobe in the individual patient with mild Alzheimer's disease and dementia with Lewy bodies (DLB) using statistical parametric mapping and visual image interpretation.. Thirty-four patients with mild late-onset Alzheimer's disease, 20 patients with early-onset Alzheimer's disease, 15 patients with DLB and 31 healthy controls were studied. All patients fulfilled appropriate clinical criteria; the DLB patients also had evidence of dopaminergic presynaptic terminal loss on 123I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane imaging. 99mTc-HMPAO SPECT brain scans were acquired on a multidetector gamma camera and images were assessed separately by visual interpretation and with SPM99.. Statistical parametric maps were significantly more accurate than visual image interpretation in all disease categories. In patients with mild late-onset Alzheimer's disease, statistical parametric mapping demonstrated significant hypoperfusion to the precuneus in 59% and to the medial temporal lobe in 53%. Seventy-six per cent of these patients had a defect in either location. No controls had precuneal or medial temporal lobe hypoperfusion (specificity, 100%). Statistical parametric mapping also demonstrated 73% of patients with DLB to have precuneal abnormalities, but only 6% had medial temporal lobe involvement.. These findings illustrate the capability of statistical parametric mapping to demonstrate reliable abnormalities in the majority, but not all, patients with either mild Alzheimer's disease or DLB. Precuneal hypoperfusion is not specific to Alzheimer's disease and is equally likely to be found in DLB. In this study, medial temporal hypoperfusion was significantly more common in Alzheimer's disease than in DLB. Statistical parametric maps appear to be considerably more reliable than simple visual interpretation of 99mTc-HMPAO images for these regions.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Brain; Brain Mapping; Case-Control Studies; Cerebral Cortex; Computational Biology; Data Interpretation, Statistical; Female; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Middle Aged; Models, Statistical; Perfusion; Software; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon; Tropanes

This was a study to evaluate the posterior cingulate sign in differential diagnosis between Alzheimer's and frontotemporal disease. The impending availability of effective treatment for Alzheimer's disease makes this differential diagnosis important.. Images of 20 patients with clinically confirmed or autopsy-proven (10 patients) Alzheimer's disease and 20 patients with clinically confirmed or autopsy-proven (7 patients) frontotemporal disease were compared with the consolidated images of 20 elderly healthy control subjects. The (99m)Tc-hexamethylpropyleneamine oxime SPECT data on brain blood flow from each patient were compared with the consolidated control image using statistical parametric mapping.. Sixteen of 20 patients with Alzheimer's disease showed the posterior cingulate sign in the form of significant blood flow reductions; 1 of 20 patients with frontotemporal disease showed the posterior cingulate sign. That patient's illness has evolved into Alzheimer's disease. The remaining 19 patients were negative for the posterior cingulate sign.. When present, the posterior cingulate sign indicates the presence of Alzheimer's disease; it is apparently absent in frontotemporal disease, thus serving as a differential diagnostic sign. It was absent in 3 patients with proven tangle-predominant Alzheimer's disease.

Topics: Aged; Alzheimer Disease; Brain; Case-Control Studies; Cerebrovascular Circulation; Dementia; Diagnosis, Differential; Frontal Lobe; Gyrus Cinguli; Humans; Predictive Value of Tests; Radiopharmaceuticals; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

The goal of the current study was to determine whether Alzheimer's disease (AD) pathology affects the limbic system of men and women differently as measured by in vivo neuroimaging. Magnetic resonance imaging (MRI) and coregistered single photon emission computed tomography (SPECT) were used to examine the limbic system in 20 men and 20 women with probable AD compared to 40 age- and education-matched normal controls (20 men, 20 women). Limbic volumes and relative perfusion values were obtained from the MR images and coregistered SPECT scans, respectively. No significant differences were found between sexes in limbic volumes or relative perfusion values in the normal controls. Many limbic regions were significantly affected in both men and women with AD compared to normal controls. However, only the men with AD displayed atrophy in the orbitofrontal cortex, middle and posterior cingulate cortices, hypothalamus, and mamillary bodies, and relative hypoperfusion in the anterior and middle cingulate cortices. Women with AD exclusively showed anterior thalamic atrophy. Separating men and women did not substantially improve diagnostic classification.

Topics: Aged; Alzheimer Disease; Case-Control Studies; Female; Humans; Limbic System; Magnetic Resonance Imaging; Male; Perfusion; Sex Characteristics; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Lateralization on neuroimaging was compared in cases of frontotemporal lobar degeneration (FTLD; n = 10) and cases of definite Alzheimer's disease (AD; n = 17). All of the cases were pathologically confirmed and semi-quantitative and statistical parametric mapping methods were employed. Seven of the 10 FTLD cases had lateralization on at least one neuroimaging modality: single photon emission computerized tomography (SPECT), MRI, or CT. All 6/6 FTLD cases with SPECT showed lateralization. MRI results generally agreed with SPECT findings. Three of 4 FTLD cases had lateralized atrophy on CT. For the AD cases, 10/17 SPECTs, 2/7 MRIs, and 1/9 CTs showed lateralized findings. Of the neuroimaging modalities utilized, SPECT was the most sensitive in detecting lateralization.

Topics: Alzheimer Disease; Cerebrovascular Circulation; Dementia; Diagnosis, Differential; Dominance, Cerebral; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

The current clinical practice of reporting images obtained with single photon emission computed tomography (SPECT) with 99mTc-d,l-hexamethylpropylene amine oxime (99mTc HMPAO) images was examined by having 16 experts evaluate the appearance of SPECT images in patients with probable Alzheimer type dementia (ATD), patients with major depressive episode (DSM-IV), and healthy volunteers. The experts rated diagnostic criteria of scan appearance in respect of importance for their individual diagnostic practice. Experts were nuclear medicine specialists, psychiatrists and physicists taking part in a European multi-centre collaborative project. They examined 158 perfusion scans and then the same perfusion scans together with statistical parametric maps (SPMs). The sensitivity of experts' diagnostic judgments was significantly and negatively correlated with the importance they attributed to reduced regional perfusion in the parietal lobes. A corresponding positive correlation was observed for diagnostic specificity against depressed and healthy volunteers. Similar results were observed with SPMs, where in addition area under the receiver operating characteristic (ROC) curve was significantly reduced with raters' increased diagnostic reliance on frontal lobe perfusion deficits. Sensitivity was greater with SPM for patients younger than 70 years and with dementia severity. The more importance experts placed on parietal (symmetrical) perfusion deficits, the less sensitive and the more specific their diagnostic judgment was. Using multiple raters in large patient samples may provide a way of identifying successful explicit diagnostic strategies for clinical image analysis.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Atrophy; Brain; Brain Ischemia; Cerebral Cortex; Depressive Disorder, Major; Diagnosis, Differential; Dominance, Cerebral; Female; Humans; Image Processing, Computer-Assisted; Male; Mental Status Schedule; Middle Aged; Parietal Lobe; Personality Inventory; ROC Curve; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

We investigated the impact of the quantitation and reconstruction protocol on clinical tasks. The performance of standard clinical reconstruction procedures in discrimination tasks related to the diagnosis of prodromal Alzheimer's disease (AD) was compared with the performance of a quantitative approach incorporating improved corrections for scatter, attenuation, intrinsic spatial resolution, and distance-dependent spatial resolution.. Seventeen normal controls (normal group), 56 subjects who did not have dementia, who did have memory problems, but who did not develop AD within 5 y of follow-up (questionable group), and 27 subjects who did not have dementia, who did have memory problems, and who did develop AD over the follow-up period (converter group) were considered in this study. (99m)Tc-hexamethylpropyleneamine oxime SPECT and MRI studies were performed for each subject at baseline. The standard quantitation protocol (STD), routinely used in our clinic, consisted of Compton window scatter correction followed by filtered backprojection with attenuation correction using a uniform attenuation map. In the improved quantitative approach (QUAN), projections were corrected for scatter by use of a general spectral method and reconstructed by use of ordered-subset(s) expectation maximization, incorporating corrections for collimator response and attenuation using both a uniform attenuation map (QUANunif) and a nonuniform attenuation map (QUANnonunif). Mean SPECT activity concentration and MRI volume were estimated for 7 structures: rostral anterior cingulate gyrus, caudal anterior cingulate gyrus, posterior cingulate gyrus, hippocampus, basal forebrain, amygdala, and the banks of the superior temporal sulcus. Data were analyzed by pairwise discriminant analysis, and performance in binary group discrimination was measured by correlated receiver-operating-characteristic analysis.. The use of QUANnonunif yielded a small but systematic improvement in discrimination accuracy for normal versus converter groups (accuracy or area under the receiver-operating-characteristic curve [Az], 0.965), normal versus questionable groups (Az, 0.973), and questionable versus converter groups (Az, 0.881) compared with the results obtained with QUANunif (Az, 0.955, 0.962, and 0.866, respectively). Discrimination performance was significantly lower (P < 0.05) with STD than with QUAN in all 3 tasks (Az with STD, 0.906, 0.878, and 0.768, respectively). MRI volume estimation led to a lower overall performance in all 3 tasks than did QUANnonunif (Az with MRI, 0.947, 0.917, and 0.872, respectively).. Improved quantitative image reconstruction with accurate compensation for scatter, attenuation, and variable collimator response led to significantly better performance in discrimination tasks related to the diagnosis of prodromal AD than did standard clinical reconstruction procedures. The use of a nonuniform brain attenuation map yields a small improvement in discrimination accuracy.

Topics: Aged; Alzheimer Disease; Brain; Dementia; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Topics: Aged; Alzheimer Disease; Cerebrovascular Circulation; Female; Fractals; Humans; Image Enhancement; Imaging, Three-Dimensional; Male; Middle Aged; Predictive Value of Tests; Pulmonary Emphysema; Radiopharmaceuticals; Reproducibility of Results; Sodium Pertechnetate Tc 99m; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Mini-Mental State Examination (MMSE) is a very useful tool for diagnosing changes in cognitive functions by the general practitioner or other medical staff who is not familiar with neuropsychological tests. On the other hand, HMPAO brain SPECT has been shown to have a high sensitivity to detect neurodegenerative processes, which lead to dementia. The correlation between both methods is unknown. We compared both methods in order to find a rational evaluation tool for the practitioner to obtain a higher efficacy and cost effective way of using both methods.. Fifty-one patients diagnosed as having Alzheimer's disease (AD) were examined. Each patient underwent MMSE analysis, as well as HMPAO brain SPECT. The severity of SPECT abnormalities was categorized into mild, moderate and severe. Statistical analysis was performed in order to evaluate the correlation between imaging findings and neuropsychological testing.. Marginal inverse correlation was found between global MMSE SPECT imaging on right and left side (p = 0.05) and the left temporal region (p = 0.05). MMSE subgroup component of orientation was highly significantly inversely associated with SPECT imaging of right and left frontal region (p > 0.0001). The MMSE subgroup of immediate memory was significantly correlated to left and right temporal regions (p = 0.001 and p = 0.002 respectively). Age was not significantly correlated to global MMSE or any of its subtest components.. MMSE score has no linear correlation to SPECT perfusion findings. In cases of abnormal orientation score subgroup SPECT imaging is not recommended. In most instances, a combination of both methods should be employed by the general practitioner for further evaluation of dementia.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Family Practice; Female; Humans; Linear Models; Male; Middle Aged; Neuropsychological Tests; Reproducibility of Results; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Technetium-99m hexamethylpropylene amine oxime (HMPAO) and (99m)Tc- N, N"-1,2-ethylene diylbis- l-cysteine diethyl ester dihydrochloride (ECD) yield significantly different images of cerebral perfusion owing to their particular pharmacokinetics. The aim of this study was to assess the topography, extension and statistical significance of these differences in Alzheimer's disease (AD). Sixty-four patients with mild to moderate AD were retrospectively selected by two European centres. Two series of patients, including 32 studied with (99m)Tc-HMPAO single-photon emission tomography (SPET) and 32 studied with (99m)Tc-ECD SPET, were matched for sex, age (+/-3 years) and severity of cognitive impairment as assessed by the Mini-Mental State Examination (MMSE) (+/-2 points), following a case-control procedure. SPET data were processed using SPM99 software (uncorrected height threshold: P=0.001). (99m)Tc-ECD SPET gave significantly higher uptake ratio values than (99m)Tc-HMPAO SPET in several symmetrical clusters, including the right and left occipital cuneus, the left occipital and parietal precuneus, and the left superior and middle temporal gyri. (99m)Tc-HMPAO SPET gave significantly higher uptake ratio values than ECD in two smaller clusters, including the hippocampus in both hemispheres. In AD, relative brain uptake of (99m)Tc-HMPAO and (99m)Tc-ECD is different in several brain regions, some of which are typically involved in AD, such as the precuneus and the hippocampus. These differences confirm the need for specific normal databases, but their impact on routine SPET reports in AD is not known and deserves an ad hoc investigation.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Brain Ischemia; Case-Control Studies; Cysteine; Female; Humans; Male; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Technetium Tc 99m Exametazime

To identify group differences in the prodromal phase of Alzheimer disease (AD) using quantitative single-photon emission computed tomography (SPECT) perfusion and magnetic resonance imaging (MRI) volume measures within specific volumes of interest.. Gerontology research unit.. There were 17 healthy controls, 56 nondemented patients with memory problems who did not develop AD during 3 to 5 years of follow-up (questionables), and 27 nondemented patients with memory problems who developed AD during follow-up (converters).. A Tc 99m hexamethylpropyleneamine oxime SPECT study and an MRI were performed in each participant at baseline. Mean SPECT activity concentration and MRI volume were estimated within 9 structures: rostral anterior cingulate, caudal anterior cingulate, posterior cingulate, hippocampus, entorhinal cortex, basal forebrain, temporal horn, amygdala, and the banks of the superior temporal sulcus. Data were analyzed using overall and pairwise discriminant analysis, and performance in pairwise group discrimination was measured using correlated receiver operating characteristic curve analysis.. The overall (3-group) discriminant function was significant for SPECT (F test, P<.001) and MRI (F test, P<.0001). For the SPECT analysis, the ranking of structures for discriminating among the 3 groups was, in order of decreasing discriminating power, caudal anterior cingulate, temporal horn, superior temporal sulcus, entorhinal cortex, hippocampus, rostral anterior cingulate, amygdala, basal forebrain, and posterior cingulate. For the MRI analysis, this ranking was entorhinal cortex, superior temporal sulcus, temporal horn, hippocampus, amygdala, caudal anterior cingulate, rostral anterior cingulate, basal forebrain, and posterior cingulate. Combining the 2 modalities yielded significantly better discrimination performance than did either alone. Furthermore, the correlation between SPECT and MRI measures was low.. Measures of structure activity concentration and volume carry independent information; both reveal group differences in prodromal AD.

Topics: Aged; Alzheimer Disease; Brain; Humans; Magnetic Resonance Imaging; Memory Disorders; Predictive Value of Tests; Radiography; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

This study tests the hypothesis that depression in patients with Alzheimer's disease (AD) is due to a specific pathogenesis rather than a reactive phenomenon. Forty-three AD patients received a psychiatrist's interview, neuropsychological assessments, and a 99mTc-hexamethyl propyleneamine oxime single photon emission computed tomography (HMPAO-SPECT). Analysis by statistical parametric mapping (SPM) showed that the depressed group had selective hypoperfusion in the bilateral anterior and posterior cingulate gyri and precuneus. Using the Hamilton Depression Rating Scale as a parameter, an inverse correlation was found between cerebral perfusion and the severity of depression. The right anterior cingulate gyrus demonstrated a most significant reduction in perfusion. These locations are akin to the imaging findings in patients with primary depression, indicating a specific pathogenesis for depression in AD.

Topics: Aged; Alzheimer Disease; Brain Mapping; Depressive Disorder; Female; Gyrus Cinguli; Humans; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The clinical differentiation of Lewy body dementia (LBD) from Alzheimer's disease (AD) may be difficult. The aim of the present study was to assess the dopamine transporter function and the perfusional pattern in LBD and AD in vivo. Twenty patients with probable LBD and 24 with probable AD underwent on 2 separate days a brain perfusional SPECT with 99mTc-ECD and a SPECT with (123)I-FP-CIT, a ligand of dopamine transporter. In LBD a significantly ( p<0.0005) lower ratio of specific (bilateral caudate nucleus, putamen) to non-specific (occipital cortex) (123)I-FP-CIT binding than in AD was reported. Perfusional data (SPM analysis) showed a significant ( p<0.001) decrease of temporo-parietal blood flow in AD versus LBD, whereas in LBD a significant ( p<0.001) occipital hypoperfusion with respect to AD was reported. Our findings confirm that dopaminergic nigrostriatal function is impaired in LBD. The selective occipital hypoperfusion in LBD needs to be further investigated.

Topics: Aged; Alzheimer Disease; Cerebrovascular Circulation; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Functional Laterality; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Membrane Glycoproteins; Membrane Transport Proteins; Mental Status Schedule; Nerve Tissue Proteins; Neuropsychological Tests; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Reductions in regional cerebral perfusion, particularly in the posterior temporo-parietal lobes, are well recognized in Alzheimer's disease. We set out to correlate perfusion changes, using (99m)Tc-HMPAO single photon emission tomography (SPET), with the pathological stage of Alzheimer's disease. The 'Braak stage' of the distribution of neurofibrillary pathology in post-mortem brains was used to classify SPET scans taken in life from a mixed (dementia and control) elderly population into the entorhinal stage (n = 23 subjects), limbic stage (n = 30 subjects) and neocortical stage (n = 36 subjects) Alzheimer's disease pathology. The SPET scans were then registered to a common, standard Talaraich space, and single template scans produced for each pathological stage. Comparison of these templates revealed an evolution in the pattern of reduction in regional perfusion. Additional comparisons were performed using earlier SPET scans obtained 5 years before death. For comparisons between templates, a threshold of 10% perfusion change was chosen so as to be clinically relevant as well as statistically significant. Reduced perfusion appears between the entorhinal and limbic stages in the anterior medial temporal lobe, subcallosal area, posterior cingulate cortex, precuneus and possibly the supero-anterior aspects of the cerebellar hemispheres. Large posterior temporo-parietal perfusion defects then appear between the limbic and neocortical stages, before finally large frontal lobe perfusion defects. The time course of these perfusion defects appears relatively long, suggesting that perfusion changes may have scope to be a diagnostic aid in staging Alzheimer's disease in life. The reduction in anterior medial temporal lobe perfusion may have future relevance on modern high resolution SPET and PET systems and also perfusion-type MRI sequences.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Female; Humans; Male; Organ Specificity; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Transient cognitive and behavioral stabilization of patients with Alzheimer's disease (AD) is the main goal of long-term acetylcholinesterase inhibitor (AChEI) therapy, but response to treatment is variable and, indeed, only some of the patients are stabilized. This is usually assessed by means of clinical and neuropsychologic scales, whereas functional neuroimaging could allow objective evaluation of the topographic correlates of the effect of therapy on brain functioning. The aim of this study was to evaluate brain perfusion changes by SPECT in AD patients during chronic AChEI therapy in relation to their cognitive evolution.. Forty-seven consecutive outpatients with mild-to-moderate probable AD (as defined by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association and the Diagnostic and Statistical Manual of Mental Disorders [4th edition criteria] and a score of > or =15 on the Mini-Mental State Examination [MMSE]) were enrolled in 2 centers over a 1-y period and underwent SPECT with 99mTc-hexamethylpropyleneamine oxime at the time of enrollment (t(0)). All of them started AChEI therapy. Nine patients were lost at follow-up, and drugs were withdrawn from 3 patients. Of the remaining 35 patients, who received regular AChEI therapy (donepezil, 5 or 10 mg/d; rivastigmine, 6 or 9 mg/d) throughout the observation period, only the 31 patients receiving donepezil were considered to avoid the possible confounding effect of different drugs. The 31 patients completed the study and a second SPECT examination was performed 15.0 +/- 3.0 mo later (t(1)). They were divided into stabilized (17 patients) and nonstabilized (14 patients) subgroups on the basis of the minimum expected annual rate of decline of the MMSE score, derived from a meta-analysis of the literature. SPECT data were analyzed by means of statistical parametric mapping.. At baseline, the stabilized and nonstabilized patients were comparable for age, sex distribution, education, MMSE scores, memory impairment (selective reminding test [SRT]), apolipoprotein E genotype, AChEI dose regimen, and SPECT findings. The SRT scores decreased significantly (P < 0.01) in the nonstabilized subgroup but not in the stabilized subgroup. No significant difference was found between the baseline and repeated SPECT data in the stabilized subgroup. In contrast, in the nonstabilized subgroup a significant perfusion reduction was found in the frontal, temporal, and parietal superficial cortex and in the occipital precuneus in the right hemisphere and in the frontal and mesial temporal cortex in the left hemisphere. On repeated SPECT, regional cerebral blood flow was significantly lower in a left frontal region in the nonstabilized group than in the stabilized group.. The regional cerebral blood flow decreases in several cortical regions in AD patients with cognitive deterioration despite long-term AChEI therapy, similar to that observed in untreated patients, whereas it remains stable in AD patients with stabilized cognitive performance during therapy.

Topics: Aged; Alzheimer Disease; Brain; Carbamates; Case-Control Studies; Cerebrovascular Circulation; Cholinesterase Inhibitors; Cognition; Donepezil; Female; Follow-Up Studies; Humans; Indans; Male; Phenylcarbamates; Piperidines; Radiopharmaceuticals; Rivastigmine; Technetium Tc 99m Exametazime; Time Factors; Tomography, Emission-Computed, Single-Photon

Alzheimer's disease (AD) is a primary degenerative disease of the brain. The prevalence increases with age, with devastating consequences for the individual and society. The aim of this study was to evaluate whether patients with early AD show an altered regional cerebral blood flow (rCBF) compared with control persons. Furthermore, we aimed to investigate the correlation between rCBF in sublobar volumes of the brain and performance on memory tests. Memory tests were chosen to evaluate episodic and semantic memory. Fourteen patients (aged 75.2+/-8.8 years) with early AD and 15 control persons (aged 71.4+/-3.2 years) were included. rCBF measurements with single-photon emission tomography (SPET) using technetium-99m hexamethylpropylene amine oxime (HMPAO) were performed. The rCBF (99m)Tc-HMPAO SPET images were spatially transformed to fit a brain atlas and normalised for differences in rCBF (Computerised Brain Atlas software). Cortical and subcortical volumes of interest (VOIs) were analysed and compared. Compared with the controls, AD patients showed a significantly lower rCBF ratio in temporoparietal regions, including the left hippocampus. The diagnostic sensitivity and specificity for AD were high in temporoparietal regions. AD patients had significantly reduced performance on semantic and, in particular, episodic memory tests compared with age-matched normative data, and their performance on several episodic tests correlated with rCBF ratios in parietal and temporal regions, including the left hippocampus. The correlation between rCBF ratio and level of episodic memory performance suggests that abnormalities in rCBF pattern underlie impaired episodic memory functioning in AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Brain Mapping; Cerebrovascular Circulation; Female; Humans; Male; Memory; Middle Aged; Radiopharmaceuticals; Reference Values; Reproducibility of Results; Statistics, Nonparametric; Technetium Tc 99m Exametazime; Time Factors; Tomography, Emission-Computed, Single-Photon

For a quantitative comparison of images obtained during (99m)Tc-hexamethylpropylene amine oxime (HMPAO) single-photon emission computed tomography (SPECT), brain activity values are usually normalized to a reference region. In studies of Alzheimer-type dementia (ATD), the cerebellum is often used as a reference region, assuming that it is spared any major pathological involvement. Statistical parametric mapping (SPM) may enhance the evaluation of SPECT scans in ATD patients. However, current SPM software only allows scaling to average whole brain activity (i.e., global normalization). The aim of this study was to develop an easily applied, objective, and reproducible method for determining average cerebellar tracer uptake so that images can be scaled specifically to cerebellar activity prior to the performance of SPM analysis. We also investigated whether cerebellar normalization increases the sensitivity and specificity of SPM analysis of ATD patients compared with global normalization.. Image files were taken from a parallel study investigating the use of SPECT as a diagnostic tool for early onset of ATD. Two methods for determining cerebellar activity were developed: one manually, using templates, the other automated, using specified coordinates entered into a Matlab routine. Group comparison of ATD patients versus controls (= healthy volunteers and depressed patients) was performed on a voxel-by-voxel basis using SPM 96 on Windows 95. Receiver operator characteristics (ROC) were computed for 20 student raters examining patient and control scans with and without single-subject SPMs.. The reduction of cerebral blood flow in the group of ATD patients appeared 1.7 times greater in spatial extent when the tracer uptake was normalized to cerebellum rather than to average whole brain activity. Computing the reverse contrast (reductions in the control group compared with ATD patients) produced clusters of significance in globally normalized images which were not manifest after normalizing to cerebellum. This is consistent with the notion that the cerebellum is spared in ATD. Analysis of the area under the ROC curve showed that cerebellar-normalized SPM produced significantly improved accuracy over perfusion scans alone.. An easily applied, objective, reproducible method was developed for normalizing images to cerebellum prior to the performance of SPM analysis. Cerebellar normalization produced more extensive abnormalities in SPM analyses of ATD patients than global normalization. Furthermore, cerebellar normalization produced marginally more accurate diagnostic results in single-scan SPM analysis of ATD patients than did global normalization.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Brain Mapping; Cerebellum; Depressive Disorder; Female; Humans; Image Processing, Computer-Assisted; Male; Mathematical Computing; Mental Status Schedule; Middle Aged; Reference Values; Reproducibility of Results; ROC Curve; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To evaluate the value of magnetic resonance (MR) perfusion imaging for diagnosis of Alzheimer disease (AD), the authors compared relative cerebral blood flow (CBF) maps obtained with MR perfusion imaging and technetium-99m hexamethyl-propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) in patients with AD.. Eight patients with AD were studied with MR perfusion imaging and HMPAO SPECT. The relative CBF maps from the two techniques were spatially coregistered, and relative CBF values in 13 cerebral gray matter regions (total, 26 regions of interest) were compared with regression analysis. To evaluate the degree of deviation of each brain region from the regression line, a P value for the residual was calculated for each region.. A significant overall correlation was seen between the relative CBF values produced by the two techniques (r = .68, P < .0001). Smaller P values for the residuals were obtained in the anterior cingulate cortex (P = .05) and posterior cingulate cortex (P < .001), indicating larger deviations in these regions. When data from these two regions were eliminated, the correlation coefficient rose to 0.80 (P < .0001).. Despite fairly large discrepancies in the anterior and posterior cingulate cortices, the relative CBF map obtained with MR imaging is generally in close agreement with the HMPAO SPECT map, suggesting that MR perfusion imaging can provide clinically useful information regarding CBF abnormalities in patients with AD.

Topics: Adult; Aged; Alzheimer Disease; Brain; Female; Humans; Magnetic Resonance Angiography; Male; Middle Aged; Middle Cerebral Artery; Radiography; Regional Blood Flow; Statistics as Topic; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Hexamethylpropyleneamine oxime (HMPAO) SPECT and 18F-FDG PET depict similar aspects of perfusion and metabolic abnormalities in Alzheimer's disease (AD), but the correspondence between them is not known in detail. We therefore used statistical parametric mapping to detect and compare abnormal brain areas objectively and quantitatively.. Twenty-six patients with probable AD (mean age +/- SD, 66 +/- 9 y; mean Mini-Mental State Examination score, 22.5 +/- 4.2) and 6 nondemented healthy volunteers (mean age, 63 +/- 11 y) were studied with HMPAO SPECT and 18F-FDG PET. All images underwent the same processing steps, including 12-mm gaussian smoothing, spatial normalization, and z transformation with respect to normal average and SD. Thresholding of z maps was used to detect abnormal voxels.. The overall correlation between PET and SPECT across the entire brain was significant but not close (average r = 0.43). The best correspondence was found in the temporoparietal and posterior cingulate association cortices. There, the number of abnormal voxels for PET correlated strongly with the number for SPECT (r = 0.90 at a z threshold of -2.25), but tracer uptake reductions were significantly more pronounced for PET than for SPECT. Discordant findings were most frequently seen in the temporobasal and orbitofrontal areas (PET low, SPECT high) and in the cerebellum, parahippocampal cortex, and midcingulate cortex (PET high, SPECT low). The correlation between dementia severity and the number of abnormal voxels was closer for PET than for SPECT. Separation of patients from healthy volunteers by counting the number of abnormal voxels was possible over a much wider range of z thresholds with PET than with SPECT.. Correspondence between 18F-FDG PET and HMPAO SPECT is limited to the main finding of temporoparietal and posterior cingulate functional impairment in mild to moderate AD. The distinction between healthy volunteers and patients is less sensitive to threshold selection with PET than with SPECT, and findings in the frontal, temporobasal, and temporomesial cortices and in the cerebellum may differ between the 2 techniques.

Topics: Aged; Alzheimer Disease; Brain; Case-Control Studies; Female; Fluorodeoxyglucose F18; Humans; Male; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

Recently, there have been studies suggesting that depressive pseudodementia would include early-stage dementing disorder. Through the comparison of the 99mTc-HMPAO single photon emission computed tomography (SPECT) image of depressive pseudodementia subjects, healthy comparison subjects, depressed subjects free of cognitive impairment, and dementia of Alzheimer's type (DAT) subjects, we aimed to see part of pathophysiology of the depressive pseudodementia of elderly patients.. Study subjects consisted of seven patients with depressive pseudodementia, seven healthy comparison subjects, seven patients with depression free of cognitive impairment, and eleven patients with DAT. Depression patients were diagnosed according to DSM-III-R. DAT patients were diagnosed by DSM III-R and NINCDS-ADRDA criteria of DAT. Other measures for assessment include Hamilton Rating Scale for Depression and Mini Mental State Exam. All underwent 99mTc-HMPAO SPECT scan. The images of each group were analyzed using statistical parametric mapping of Friston, which compares the images on voxel-by-voxel basis.. The results were as follows (1) The DAT group showed significant decreases of cerebral blood flow (CBF) in the right frontal, right temporal region, and both parietal regions as compared with control group (P < 0.05). (2) The depression group showed a significant decrease of CBF in the left frontal region as compared with control group (P < 0.05). (3) The depressive pseudodementia group showed significant decreases of CBF in both parietal regions as compared with control group (P < 0.05). (4) The depressive pseudodementia group showed significant decreases of CBF in the right temporal region and both parietal regions as compared with depression group (P < 0.05). (5) The DAT group showed significant decreases of CBF in the right temporal region, both frontal regions, and both parietal regions as compared with depressive pseudodementia group (P < 0.05).. The small number of subjects may make it difficult to generalize from our results. Because decreased CBF in depressive pseudodementia is found while the subjects were depressed, we cannot tell whether it is a state marker or a trait marker.. The depressive pseudodementia group showed decreased CBF in the temporo-parietal region, similar to that of the DAT group and different from that of the depression group.

Topics: Aged; Alzheimer Disease; Brain; Depressive Disorder; Factitious Disorders; Female; Frontal Lobe; Humans; Male; Parietal Lobe; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

Dual-isotope imaging can allow simultaneous assessment of brain perfusion using a 99mTc-labeled tracer and neurotransmission using an 123I-labeled tracer. However, the images are affected by scatter, cross talk, attenuation, distance-dependent collimator response (DCR), and partial-volume effect. We determined the accuracy and precision of activity quantitation in simulated normal and pathologic studies of simultaneous 123I/99mTc brain SPECT when compensating for all degrading phenomena.. Monte Carlo simulations were performed using the Zubal brain phantom. Contamination caused by high-energy 123I decay photons was incorporated. Twenty-four 99mTc and 123I activity distributions were simulated on the basis of normal and pathologic patient activity distributions. Cross talk and scatter were corrected using a new method based on a multilayer perceptron artificial neural network (ANN), as well as by the asymmetric window (AW) approach; for comparison, unscattered (U) photons of 99mTc and 123I were recorded. Nonuniform attenuation and DCR were modeled in an iterative ordered-subset expectation maximization (OSEM) algorithm. Mean percentage biases and SDs over the 12 normal and 12 pathologic simulated studies were computed for each structure with respect to the known activity distributions.. For 123I, AW + OSEM yielded a bias of 7% in the cerebellum, 21% in the frontal cortex, and 36% in the corpus callosum in the simulated normal population. The bias was increased significantly in the striata of simulated pathologic studies (P < 0.05). The bias associated with ANN was significantly lower (<9% in these brain structures, P < 0.05). For 99mTc with AW + OSEM, the bias was 60% in the corpus callosum, 36% in the striata, and 18%-22% in the cortical lobes in the simulated normal population. This bias was <11% in all brain structures with ANN. In the simulated pathologic population, the bias associated with AW increased significantly in the cortical lobes to 55% (P < 0.05), although it did not change significantly with ANN.. The accuracy and variability over simulated normal and pathologic studies of both 99mTc and 123I activity estimates were very close with ANN to those obtained with U + OSEM. ANN + OSEM is a promising approach for absolute activity quantitation in simultaneous 99mTc/123I SPECT.

Topics: Alzheimer Disease; Benzamides; Brain; Cerebellum; Cerebral Cortex; Cerebrovascular Circulation; Corpus Callosum; Humans; Iodine Radioisotopes; Monte Carlo Method; Neural Networks, Computer; Parkinson Disease; Phantoms, Imaging; Putamen; Pyrrolidines; Radiopharmaceuticals; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To compare the utility of temporal lobe magnetic resonance imaging (MRI) and single-photon emission tomography (SPET) scanning in discriminating between subjects with Alzheimer's disease (AD) and age-matched controls.. Thirty subjects with NINCDS-ADRDA AD (23 probable AD, 5 possible AD, 2 definite AD) and 22 age- and sex-matched controls underwent T1-weighted coronal MRI scanning (0.3 T) and technetium 99m-HMPAO SPET scanning. MRI scans were analyzed using a digitizer system with volumes of hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, and whole cerebral cortex calculated. From SPET scans, regional cerebral blood flow (rCBF) was assessed in anterior and posterior frontal, parietal, occipital, and mesial temporal cortex using a region of interest analysis with the cerebellum as a reference area.. Using MRI, the areas that best separated groups were left hippocampal and left amygdala volume, resulting in correct classification (patient vs. control) in 79% of cases (sensitivity 77%, specificity 82%). Exactly the same proportion of subjects were correctly classified by SPET, with the most discriminating rCBF changes being left parietal and right posterior frontal. Combining information from both scans improved the proportion of correctly classified subjects in a discriminant function to 90% (sensitivity 93%, specificity 86%; only 2 AD and 3 controls misclassified). All AD subjects had abnormalities on MRI and/or SPET (sensitivity for combined examinations 100%), while abnormalities on both MRI and SPET had a positive predictive value of 100% for dementia (including the detection of one control subject who later had dementia). Significant correlations between MRI and SPET measures were seen in control subjects but not in patients.. Both 0.3 T MRI and single rotating gamma camera SPET were equally useful in separating AD subjects from age-matched controls, although the combination of both significantly enhanced discrimination. In particular, all AD subjects had abnormalities on either MRI or SPET and both techniques may have an important role in assisting with clinical diagnosis, though replication in other centers and examination of differentiation of AD from other causes of dementia need to be examined.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Case-Control Studies; Dementia; Diagnosis, Differential; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Predictive Value of Tests; Radiopharmaceuticals; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

We investigated the neural substrate of the delusion of theft in patients with Alzheimer's disease (AD). Nine AD patients with only one type of delusion (delusions of theft) and nine age, cognitive function-matched AD patients without any type of delusions were selected from 334 consecutive outpatients of Ehime University Hospital. All subjects underwent (99m)Tc-HMPAO SPECT scanning, and SPECT images were analyzed by Statistical Parametric Mapping (SPM). AD patients with delusions of theft showed significant hypoperfusion in the right medial posterior parietal region compared to patients without delusions. Our data suggest that attention impairment or lack of awareness of illness caused by right parietal dysfunction might play a role in producing the delusion of theft.

Topics: Age Factors; Aged; Alzheimer Disease; Case-Control Studies; Cerebrovascular Circulation; Cognition Disorders; Delusions; Educational Status; Female; Humans; Male; Neuropsychological Tests; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Theft; Tomography, Emission-Computed, Single-Photon

Brain SPECT and PET investigations have showed discrepancies in Alzheimer's disease (AD) when considering data deriving from deeply located structures, such as the mesial temporal lobe. These discrepancies could be due to a variety of factors, including substantial differences in gamma-cameras and underlying technology. Mesial temporal structures are deeply located within the brain and the commonly used Filtered Back-Projection (FBP) technique does not fully take into account either the physical parameters of gamma-cameras or geometry of collimators. In order to overcome these limitations, alternative reconstruction methods have been proposed, such as the iterative method of the Conjugate Gradients with modified matrix (CG). However, the clinical applications of these methods have so far been only anecdotal. The present study was planned to compare perfusional SPECT data as derived from the conventional FBP method and from the iterative CG method, which takes into account the geometrical and physical characteristics of the gamma-camera, by a correlative approach with neuropsychology.. Correlations were compared between perfusion of the hippocampal region, as achieved by both the FBP and the CG reconstruction methods, and a short-memory test (Selective Reminding Test, SRT), specifically addressing one of its function. A brain-dedicated camera (CERASPECT) was used for SPECT studies with 99mTc-hexamethylpropylene-amine-oxime in 23 consecutive patients (mean age: 74.2 +/- 6.5) with mild (Mini-Mental Status Examination score > or =15, mean 20.3 +/- 3), probable AD. Counts from a hippocampal region in each hemisphere were referred to the average thalamic counts.. Hippocampal perfusion significantly correlated with the MMSE score with similar statistical significance (p < 0.01) between the two reconstruction methods. Correlation between hippocampal perfusion and the SRT score was better with the CG method (r = 0.50 for both hemispheres, p < 0.01) than with the FBP method (r = 0.37 and 0.43, respectively for the right and left hemisphere, p < 0.05 and p < 0.02). The bootstrap procedure showed that such correlation indexes were statistically different both in the right (p < 0.01) and in the left (p < 0.05) hemisphere.. These results are interpreted as a better performance of the CG reconstruction method in correctly detecting counts from hippocampal ROI. By using the same gamma-camera or collimator, alternative methods for brain SPECT reconstruction may improve quality of data and then help SPECT diagnostic accuracy.

Topics: Aged; Alzheimer Disease; Brain; Female; Humans; Image Processing, Computer-Assisted; Male; Memory; Middle Aged; Technetium Tc 99m Exametazime; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

This study describes a method for quantifying cerebral blood flow (CBF) distribution in Alzheimer's disease (AD) from SPECT images obtained with (99m)Tc-hexamethylpropyleneamine oxime (HMPAO) by 3-dimensional fractal analysis (3D-FA).. HMPAO SPECT was performed on 68 patients with probable AD and 14 healthy control subjects. We delineated the CBF images using 4 cutoff levels (35%, 40%, 45%, and 50% of the maximal voxel radioactivity) and measured the total number of voxels in the areas surrounded by the contours obtained with each cutoff level. We calculated fractal dimensions from the relationship between the total number of voxels and the cutoff levels transformed into natural logarithms.. The fractal dimensions (mean +/- SD) for patients with probable AD and healthy subjects were 0.74 +/- 0.33 and 0.52 +/- 0.09, respectively. A significant difference in the fractal dimension was found between groups (P = 0.001). Statistically significant correlations were obtained between the fractal dimension and the Mini-Mental State Examination score (r = -0.598; P < 0.0001) and between the fractal dimension and the AD Assessment Scale (r = 0.670; P < 0.0001). The fractal dimensions for subjects with clinical dementia rates (CDRs) of 0, 1, 2, and 3 were 0.52 +/- 0.09, 0.63 +/- 0.21, 0.77 +/- 0.23 (P < 0.05 vs. the group with a CDR of 1), and 1.43 +/- 0.49 (P < 0.0001 vs. the group with a CDR of 2), respectively.. Quantification of CBF distribution on SPECT images in AD was possible using 3D-FA. The fractal dimension was well correlated with the cognitive impairment, as assessed in neuropsychologic tests. 3D-FA may be a useful method for objectively evaluating the progression of AD.

Topics: Aged; Alzheimer Disease; Cerebrovascular Circulation; Female; Fractals; Humans; Imaging, Three-Dimensional; Male; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The central hypothesis of the study which has been carried out as part of the NRP38 program, is that perturbations of brain energy metabolism are critically involved in the neurodegeneration occurring in Alzheimer's disease (AD) and that they may correlate with early cognitive dysfunctioning. In the present multidisciplinary study we set out to monitor brain energy metabolism using FDG-PET and HMPAO-SPECT imaging in a cohort of individuals over 65 years of age, drawn from the general population. HMPAO-SPECT imaging, which is a simpler and more widely accessible imaging procedure than FDG-PET, was performed under basal conditions and during the performance of a cognitive task (verbal fluency test). Three groups were studied. Two groups (groups I and II) included individuals age 65 or more, with no cognitive impairment and carrying an APOE4 positive or APOE4 negative phenotype, respectively; a third group (group III) included patients with clinical signs of AD. Each subject entering the study underwent an FDG-PET, an HMPAO-SPECT and an extensive battery of neuropsychological tests which assess various aspects of cognitive functioning, with a strong emphasis on working memory, divided attention and executive functions. A total of 101 participants were submitted to brain imaging and neuropsychological testing. Among these, 60 participants received the same set of imaging and neuropsychological tasks 24-36 months after the first set (phase II). In this article, we present a preliminary analysis performed on ten subjects from groups I and II and nine subjects from group III: activation (verbal fluency task) induced a specific pattern of increase in HMPAO retention (including BA 9/10, BA 18 bilaterally and right BA 17). In contrast to controls, in nine AD subjects no significant differences in HMPAO retention were observed when comparing activation and basal conditions. The cellular and molecular mechanisms that underlie the retention of HMPAO, the tracer used for single photon emission computed tomography (SPECT) imaging, has been studied in vitro in purified preparations of neurons and astrocytes with the aim of investigating the contribution of different cell types to hexamethyl-propyleneamineoxime labeled with technetium-99m (99mTc-HMPAO) retention in vitro. Results show that 99mTc-HMPAO retention predominates in astrocytes over neurons by a factor of approximately 2.5. Diethyl maleate, ethacrynic acid and buthionine sulfoximine, three agents which significa

Topics: Aged; Alzheimer Disease; Animals; Animals, Newborn; Astrocytes; Blood-Brain Barrier; Brain; Cells, Cultured; Energy Metabolism; Humans; Mice; Neurons; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Verbal Behavior

To investigate the value of Tc-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) single photon emission computed tomography (SPECT) as a diagnostic test for Alzheimer's disease.. Tc-99m HMPAO SPECT was performed on 140 patients and 20 controls. A final diagnosis was established for 115 patients, 58 of whom had Alzheimer's disease. The probability of AD was determined for seven scintigraphic patterns. The probability of Alzheimer's disease was 14% for patients with memory loss and normal perfusion. For patients with abnormal perfusion patterns, the probability of Alzheimer's disease was 87% with bilateral temporoparietal defects, 73% with bilateral temporoparietal defects plus additional defects, 62% with a unilateral temporoparietal defect, 33% with a frontal defect only, 0% with other large defects, and 0% with multiple small cortical defects. In 115 patients with the complaint of memory loss or cognitive abnormalities, bilateral temporoparietal hypoperfusion with or without additional hypoperfusion was more frequent than other scintigraphic patterns in patients with Alzheimer's disease. Tc-99m HMPAO SPECT offers the clinician the possibility of differentiating dementias on the basis of differences in perfusion patterns.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Female; Humans; Male; Middle Aged; Probability; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The purpose of the current study was to examine the relation between regional cerebral blood flow (rCBF) and negative symptoms (NS) in patients with dementia of Alzheimer type (DAT).. Negative symptoms in neuropsychiatric disorders were associated with altered rCBF in frontal cortex.. Twenty-five subjects with a diagnosis of DAT were administered the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptom Scale, the Hamilton Rating Scale for Depression, and the Mini-Mental State Examination. The subjects were divided into two groups by means of a median split with regard to NS severity (high NS group, N = 12; low NS group, N = 13). Each patient underwent a single photon emission tomography scan using 99mTc-HMPAO at rest. Cortical and subcortical regions of interest were symmetrically defined in each hemisphere. Cortical-to-cerebellar perfusion ratios were established quantitatively using ADAC software.. High NS group subjects had a significantly lower rCBF than low NS group subjects in the frontal cortex and cingulate gyrus (MANOVA: p = 0.022) as a result of differences in the dorsolateral prefrontal cortex bilaterally (right: F = 12.12, p = 0.002; left: F = 6.55, p = 0.02) and in the frontal cortex, mainly in the right hemisphere (right: F = 6.33, p = 0.02; left: F = 3.26, p = 0.08). For all the subjects (N = 25), there were negative correlations between the SANS total score and rCBF, most prominently in the dorsolateral prefrontal cortex bilaterally (right: r = -0.48, p <0.01; left: r = -0.49, p = 0.01). No significant correlation was found between rCBF in any of the regions of interest and either the Mini-Mental State Examination or the Hamilton Rating Scale for Depression scores.. This study indicates that decreased perfusion in the frontal cortex is associated with NS severity but not with measures of cognitive impairment or depressive symptoms in DAT patients. These results support the hypothesis that the frontal lobes may be involved in the cause of NS in DAT, and they underscore the importance of NS evaluation in neuroimaging studies.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Depression; Dominance, Cerebral; Female; Frontal Lobe; Humans; Male; Mental Status Schedule; Personality Inventory; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The authors describe a patient in whom neuroimaging using Tc-99m HMPAO SPECT, F-18 fluorodeoxyglucose (F-18 FDG) coincidence imaging, and magnetic resonance imaging (MRI) identified an anterior choroidal artery infarction. Neuroimaging played a critical role in confirming this diagnosis, because the patient had symptoms of progressive cognitive decline and satisfied the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease (AD).. Tc-99m HMPAO brain SPECT was performed using a triple-head gamma camera. F-18 FDG scanning was obtained 40 minutes after intravenous injection of 5 mCi F-18 FDG using a coincidence camera. A brain MRI scan was performed using a 1.5-Tesla scanner.. Tc-99m HMPAO SPECT showed focal hypoperfusion to the right parahippocampal cortex. F-18 FDG coincidence imaging showed a more extensive reduction in glucose metabolism compared with SPECT. The MRI scan confirmed the presence of a small segmental choroidal artery infarction. The Tc-99m HMPAO and F-18 FDG scans were not consistent with AD.. This case illustrates the value of the regional cerebral blood flow SPECT for evaluating memory impairment in the elderly. Decreased regional cerebral blood flow to the posterior temporoparietal region is consistent with AD, whereas regional cerebral blood flow diminution in a vascular territory is consistent with vascular dementia. In this case, the patient was clinically diagnosed with AD, and SPECT was performed to establish the baseline regional cerebral blood flow before the cholinesterase inhibitor donepezil was administered. An infarction was diagnosed on the regional cerebral blood flow brain SPECT scan, which was later confirmed by MRI. Infarctions of the parahippocampal cortex may resuft in memory impairment, which can appear clinically similar to AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Cerebral Infarction; Cerebrovascular Circulation; Cognition Disorders; Diagnosis, Differential; Female; Fluorodeoxyglucose F18; Humans; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Progressive aphasia is a prominent clinical feature of several neurodegenerative disorders. This study used hexylmethylpropylene amineoxine (HMPAO) single photon emission computed tomography (SPECT) to estimate blood flow in areas of the brain that mediate language in patients with progressive aphasia and matched control subjects. The patient population consisted of four men and 12 women with a mean +/- SD age of 69.1 +/- 7.6. Of these, eight were classified as having a nonfluent form of aphasia, whereas the other eight had a fluent form. The patients were compared to 16 healthy volunteers who were studied with an identical protocol. The SPECT images of the brain were acquired with 740 MBq (20 mCi) of Tc-99m-labeled HMPAO on a triple-headed gamma camera equipped with fan beam collimators. The images were analyzed with a set of standardized templates. Mean counts per pixel in 33 regions of interest were compared to the mean counts in the whole supratentorial brain. A laterality index was determined for homotopic regions using the equation 100 x (R - L)/(1/2 x (R - L)). Patients with progressive aphasia had several regions of significantly decreased HMPAO uptake in the left cortex when compared to the homotopic regions on the right. The most prominent deficit in the nonfluent group, as determined by the laterality index, were found in the left dorsolateral prefrontal region (p < 0.05), whereas the most prominent deficits in the group with fluent aphasia were found in the left temporal and parietal language centers (p < 0.05). The left subcortical nuclei were differentially affected, particularly in patients with nonfluent aphasia. The HMPAO SPECT indicates that multiple regions of the left hemisphere are dysfunctional in patients with progressive aphasia. The pattern of perfusion deficits in patients with fluent aphasia appears to be distinct from the pattern in patients with nonfluent aphasia.

Topics: Aged; Alzheimer Disease; Aphasia, Broca; Aphasia, Wernicke; Brain Mapping; Cerebral Cortex; Dominance, Cerebral; Female; Follow-Up Studies; Humans; Male; Middle Aged; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Delusional behavior and thinking are common symptoms in Alzheimer's disease (AD). In the past, these delusions have been considered to be psychotic complications of global neurologic dysfunction. Recently, authors have suggested that content-specific delusions in AD are associated with discrete regional abnormalities of the right hemisphere.. This study compared 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT images of a group of AD patients with a similar autobiographic delusion with a group of AD patients without delusions and a group of AD patients with a range of delusions but without autobiographic content. The reconstructed SPECT data were compared using a statistical parametric mapping technique.. The autobiographic AD group had a significant area of hypoperfusion in the right frontal lobe when compared with the 2 other groups. The area of hypoperfusion included parts of Brodmann's areas 9 and 10. Region 9 has been identified previously as having a role in episodic memory retrieval.. This result suggests that autobiographic delusions in AD may have an identifiable neuropsychologic mechanism and that it may be possible to identify an organic cause in some patients using 99mTc-HMPAO SPECT.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Analysis of Variance; Brain; Brain Mapping; Delusions; Female; Humans; Male; Mental Status Schedule; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most frequent neurodegenerative cognitive disorders. However, FTD remains poorly recognised clinically. The use of (99m)HmPAO-single photon emission computed tomography (SPECT) has been demonstrated in the differentiation of AD and FTD. Nethertheless, there are very few comparative studies designed to assess its precise value in this differential diagnosis. The aim was to determine a simple decision rule, deduced from statistical analysis, which, if applied to regions of interest (ROIs) and mini mental state examination (MMSE), could improve the predictive value of SPECT in differential diagnosis between AD and FTD.. Forty patients, 20 with probable AD and 20 with probable FTD were included. All patients underwent brain SPECT imaging, after an intravenous injection of (99m)Tc HmPAO-(555mBq). For each patient, 20 ROIs were determined on the Fleishig's slice and their activity was normalised to the mean cerebellar activity. Bivariate analysis (Wilcoxon rank tests) and multivariate analysis (stepwise discriminant analysis) were performed to determine the subgroup of variables able to give the highest predictive value for this differential diagnosis. A simple decision rule was built from a predictive score derived by factorial discriminant analysis.. As previously described, the fixation defect was found in frontal regions of interest (ROIs) in FTD and in the left temporoparietal-occipital ROIs in AD. Among the 21 variables, five were finally selected: right median frontal, left lateral frontal, left tempoparietal, left temporoparietal-occipital areas, and MMSE. One hundred per cent of patients with FTD were correctly classified by the decision rule (20/20 patients) and 90% of patients with AD (18/20).. AD and FTD are differentiated by SPECT. Automatic classification based on a decision rule deduced from factorial discriminant analysis could enhance its performance.

Topics: Alzheimer Disease; Brain; Dementia; Discriminant Analysis; Frontal Lobe; Humans; Multivariate Analysis; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

Perfusion and metabolic studies in patients with Alzheimer's disease (AD) have so far yielded conflicting results on the functional status of the hippocampal region, whose deep location in the brain makes it critical to optimize the image-reconstruction technique employed in emission tomography. We used a brain-dedicated device (CERASPECT) to perform single photon emission computed tomography (SPECT) studies with 99mTc-hexamethylpropylene-amine-oxime in 22 consecutive patients (mean age: 74+/-6.5 years) with mild [mini-mental status examination (MMSE) score > or =15, mean 20.8+/-3.2], probable AD. The control subjects were 11 healthy elderly people (mean age: 70.5+/-6.5 years). In patients, the total score on the selective reminding test (SRT) was used as an index of memory function. Counts from a hippocampal and a temporoparietal region of interest in each hemisphere were referred to the average thalamic counts. To optimize SPECT images, we used conventional filtered back-projection (FBP) reconstruction and a new iterative method of conjugate gradients (CG), which takes into account the geometrical and physical characteristics of the gamma-camera. Hippocampal perfusion in the two hemispheres was significantly lower in patients than in control subjects, regardless of which reconstruction method was used, and correlated with the MMSE score. The correlation between hippocampal perfusion and the SRT score was significantly (bootstrap procedure) higher with the CG method than with the FBP method (CG: r=0.52 and 0.54; FBP: r=0.39 and 0.47, for the right and left hemisphere, respectively). These results show hippocampal hypoperfusion in patients with mild AD, a correlation between hippocampal perfusion and the severity of cognitive impairment, and enhanced identification of these subtle perfusional changes with the use of an alternative image-reconstruction method that improves the spatial resolution of SPECT images.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Atrophy; Case-Control Studies; Cerebrovascular Circulation; Cognition Disorders; Female; Hippocampus; Humans; Male; Middle Aged; Parietal Lobe; Radiopharmaceuticals; Severity of Illness Index; Technetium Tc 99m Exametazime; Temporal Lobe; Thalamus; Tomography, Emission-Computed, Single-Photon

The aims of this study were to develop an objective method for assessing rCBF deficits using a statistical image analysis protocol and to validate its effective use in clinical practice. 99Tcm-HMPAO brain SPET images were acquired for 40 normal subjects, 10 patients with Alzheimer's disease and 10 patients with depression. Automated image registration was used to standardize the size and shape of the brain structures for all subjects. The images of the first 30 normal subjects were used to construct a normal database. The CBF images of the other 10 normal subjects and the 20 patients were compared voxel by voxel with the normal database to map CBF abnormalities by statistical evaluation. The results were compared with the clinical reports of CBF images. The expert system detected all rCBF deficits reported by the nuclear physicians. Some additional areas with special information, like atrophy and bilateral asymmetry, were also identified by the expert system. We conclude that this expert system can delineate CBF deficits with sufficiently high accuracy, differentiating normal from abnormal CBF images using voxel-based comparisons. The use of an expert system improves rCBF SPET image evaluation.

Topics: Aged; Alzheimer Disease; Atrophy; Brain; Cerebral Arteries; Cerebrovascular Circulation; Data Interpretation, Statistical; Databases, Factual; Depression; Expert Systems; Humans; Image Interpretation, Computer-Assisted; Image Processing, Computer-Assisted; Middle Aged; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

This study assessed the accuracy and reliability of Automated Image Registration (AIR) for standardization of brain SPECT images of patients with Alzheimer's disease (AD). Standardized cerebral blood flow (CBF) images of patients with AD and control subjects were then used for group comparison and covariance analyses.. Thirteen patients with AD at an early stage (age 69.8+/-7.1 y, Clinical Dementia Rating Score 0.5-1.0, Mini-Mental State Examination score 19-23) and 20 age-matched normal subjects (age 69.5+/-8.3 y) participated in this study. 99mTc-hexamethyl propylenamine oxime (HMPAO) brain SPECT and CT scans were acquired for each subject. SPECT images were transformed to a standard size and shape with the help of AIR. Accuracy of AIR for spatial normalization was evaluated by an index calculated on SPECT images. Anatomical variability of standardized target images was evaluated by measurements on corresponding CT scans, spatially normalized using transformations established by the SPECT images. Realigned brain SPECT images of patients and controls were used for group comparison with the help of statistical parameter mapping. Significant differences were displayed on the respective voxel to generate three-dimensional Z maps. CT scans of individual subjects were evaluated by a computer program for brain atrophy. Voxel-based covariance analysis was performed on standardized images with ages and atrophy indices as independent variables.. Inaccuracy assessed by functional data was 2.3%. The maximum anatomical variability was 4.9 mm after standardization. Z maps showed significantly decreased regional CBF (rCBF) in the frontal, parietal and temporal regions in the patient group (P < 0.001). Covariance analysis revealed that the effects of aging on rCBF were more pronounced compared with atrophy, especially in intact cortical areas at an early stage of AD. Decrease in rCBF was partly due to senility and atrophy, however these two factors cannot explain all the deficits.. AIR can transform SPECT images of AD patients with acceptable accuracy without any need for corresponding structural images. The frontal regions of the brain, in addition to parietal and temporal lobes, may show reduced CBF in patients with AD even at an early stage of dementia. The reduced rCBF in the cortical regions cannot be explained entirely by advanced atrophy and fast aging process.

Topics: Aged; Alzheimer Disease; Brain; Cerebrovascular Circulation; Female; Humans; Image Processing, Computer-Assisted; Male; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

The purpose of this study was to evaluate the effects of various covariants on the distribution pattern of Tc-99m HMPAO in patients with Alzheimer's disease by correlation analysis. Twenty patients with Alzheimer's disease and 15 age matched normal subjects participated. Tc-99m HMPAO brain SPECT and x ray computed tomography (CT) were acquired for each subject. SPECT images were transformed to a standard size and shape by automated image registration (AIR) and were used for group comparison by means of SPM96. Voxel based covariance analysis was performed on standardised images taking the age of patients, severity of disease (clinical dementia rating scale, mini mental state examination, physical self maintenance scale), and atrophy indices as variables. There was significantly decreased regional cerebral blood flow (rCBF) in the frontal, parietal, and temporal regions in the patient group (p<0.001), more marked in those patients having severe dementia. Covariance analysis disclosed that aging and severity of disease have a pronounced effect on rCBF, especially that of the left parietal region.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain Mapping; Humans; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The diagnostic potential of technetium-99m hexamethylpropylene amine oxime (HMPAO) following systemic administration of the cerebral vasodilator acetazolamide (acetazolamide test) was evaluated by regional cerebral blood flow (rCBF) single-photon emission tomography (SPET) in patients with Alzheimer's disease (AD) or vascular dementia (VD). An initial, high-resolution SPET study was performed with 99mTc-HMPAO, and after 2 days the patients were re-evaluated with 99mTc-HMPAO following systemic administration of acetazolamide. Reconstructed SPET slices were evaluated visually and semiquantitatively by a semi-automatic rCBF map method. When 99mTc-HMPAO alone was used, bilateral hypoperfusion was found in the temporal and/or parietal regions in 33% (6/18) of the VD patients and in 70% (23/33) of the AD patients. The corresponding data obtained by quantitative evaluation were 41% (7/17) and 71% (15/21), respectively. The vascular reserve capacity, as determined with the acetazolamide test, was preserved visually in 22% (4/18) and quantitatively in 29% (5/17) of the VD patients, but in 73% (24/33) and 76% (16/21) of the AD patients. The differences in the perfusion patterns between the VD and AD patients were statistically significant (P<0.01, Fischer's exact test). Of the VD patients with hypoperfusion (bilateral temporal and/or parietal), 4/6 (67%, visual evaluation) and 4/7 (57%, quantitative evaluation) had a decreased vascular reserve capacity as determined with the acetazolamide test. In the AD group of patients the corresponding results were 3/23 (13%) and 4/15 (27%). It is concluded that the acetazolamide test is promising in rCBF SPET to differentiate VD from AD.

Topics: Acetazolamide; Aged; Alzheimer Disease; Brain; Cerebrovascular Circulation; Dementia, Vascular; Diagnosis, Differential; Female; Humans; Image Processing, Computer-Assisted; Male; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Vasodilator Agents

In this study the neuropsychological status of patients with Alzheimer's disease (AD) was correlated with quantitative electroencephalography (qEEG) and regional cerebral blood flow (rCBF) both in the cortex and in deep gray matter structures.. Forty-three outpatients (mean age 72.4 +/- 7.5 y) with probable AD underwent 99mTc-hexamethyl propyleneamine oxime SPECT with a brain-dedicated gamma camera and qEEG (relative values) within 1 mo. Preliminary factorial analysis with promax rotation identified four qEEG bands (2-5.5, 6-7.5, 8-11.5 and 12-22.5 Hz, with no distinction as to topography) and six SPECT regions (the two thalami together, the two parietal cortices together, the right temporal cortex, the right hippocampus, the left hippocampus and the remaining cortical areas together) as the variables with highest statistical power. All these variables and the Mini-Mental Status Examination score (MMSE, a sensitive marker of neuropsychological deficit) were processed by a final factorial analysis and multivariate analysis of variance.. Both the 2-5.5 Hz and the 8-11.5 Hz powers were correlated with the perfusion level in the parietal regions of interest (ROls) (P = 0.0009), whereas the 2-5.5 Hz power was correlated with the right hippocampal perfusion level (P = 0.007). The MMSE score was significantly correlated with the perfusion level, both in the right (P = 0.006) and in the left (P = 0.004) hippocampal ROls and in the parietal ROls (P = 0.01); moreover, it was correlated with both the 2-5.5 Hz (P = 0.0005) and the 8-11.5 Hz (P = 0.004) power.. rCBF (bilateral parietal perfusion) and qEEG (especially the slowest frequencies, i.e., 2-5.5 Hz) are confirmed to be good descriptors of AD severity. It is especially noteworthy that bilateral hippocampal CBF was the perfusional index best correlated with the MMSE as well as being significantly correlated to qEEG. Hippocampal SPECT imaging appears to be a promising index to improve characterization of AD in respect to other forms of primary degenerative dementia and may be proposed as a marker for evaluating the effects of pharmacotherapy of AD at the neuronal level.

Topics: Aged; Alzheimer Disease; Brain; Cerebrovascular Circulation; Electroencephalography; Factor Analysis, Statistical; Female; Humans; Male; Multivariate Analysis; Neuropsychological Tests; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The primary objective of this study was to test hypotheses about the relationship between HMPAO-SPECT findings and probable Alzheimer's disease (DAT) in a relatively large sample of patients diagnosed according to DSM-III-R. SPECT patterns of 20 controls and 116 DAT patients were investigated. Left and right frontal, temporal, parietal and occipital regions of the brain were rated as showing a hypoperfusion or not. A wide variety of patterns were found and these are described in detail below. In DAT patients, temporal and/or parietal regions were affected significantly more often (88%, p > 0.001) than frontal and/or occipital regions (70%). A bilateral temporoparietal pattern, which has been repeatedly reported as typical for DAT, was observed in 48% of DAT patients, but also in 25% of controls, and did not differentiate significantly between these two groups (p > 0.05). Conversely, more than three regions with hypoperfusion were observed significantly more often in DAT patients (48%, p < 0.01) than in controls (10%). In DAT patients, the number of regions with hypoperfusion correlated significantly with the score of the Mini Mental State Examination (MMSE, r = 0.33, p < 0.001). The frequency of at least one hypoperfusion was approximately equal in left and right hemispheres (77% vs. 73%, p = 0.2). The hypothesis that cognitive decline in DAT starts in the temporal regions was tested in 14 SPECT patterns showing only one region with hypoperfusion. In 12 of these patterns, a temporal region was in fact affected (p < 0.001). Whereas hypoperfusion in frontal areas was not accompanied by a significantly lower MMSE than when only temporoparietal regions were affected, MMSE scores were significantly lower when occipital regions were affected in addition to temporoparietal regions (p < 0.05). The clinical use of SPECT findings was tested in discriminating analyses with the MMSE and a delayed recall test as additional predictors of DAT. Whereas the MMSE and the delayed recall test differentiated significantly between DAT patients and controls, SPECT findings yielded no further differentiation. In conclusion, the theoretical and clinical implications of SPECT findings and their relationships to other physiological and psychological variables deserve further investigation.

Topics: Aged; Alzheimer Disease; Brain; Case-Control Studies; Cerebrovascular Circulation; Chi-Square Distribution; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Predictive Value of Tests; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The aim of this study was to compare the regional cerebral blood flow measurements studied by SPECT in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) to determine the contribution of SPECT to the differential diagnosis of these two diseases.. SPECT analysis with 99mTc-hexamethyl propyleneamine oxime (HMPAO) was performed in 20 patients with probable DLB, 20 patients with probable AD and 20 patients with idiopathic Parkinson's disease (IPD). Ten pairs of regions of interest were analyzed. Tracer uptake was expressed as a corticocerebellar activity ratio.. Compared with IPD, in the DLB group there was a global decrease of HMPAO uptake in cortical regions of interest except in the posterior frontal and occipital regions; in the AD group there was limited left temporal and parietal hypoperfusion. In the DLB group, frontal HMPAO uptake was significantly lower than in the AD group. Two predictive scores were established by a factorial discriminant analysis from six left cortical indices (medial frontal, lateral frontal, posterior frontal, temporoparietal, parietal and parietooccipital) and the Mini-Mental State Examination, which correctly classified 53 of 60 patients (88%) (DLB, 18 of 20; AD, 16 of 20; IPD, 19 of 20).. These findings indicate the presence of diffuse cortical abnormalities in DLB and suggest that SPECT may be useful in discriminating in vivo DLB from AD, revealing mainly frontal hypoperfusion in the former group. We estimate that SPECT study increases the possibility of separating DLB and AD because both disorders share different patterns of cerebral blood flow abnormality.

Topics: Aged; Alzheimer Disease; Brain; Cerebral Cortex; Cerebrovascular Circulation; Data Interpretation, Statistical; Diagnosis, Differential; Humans; Middle Aged; Parkinson Disease; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To compare brain perfusion and synaptic density in Alzheimer's disease assessed using I-123 iomazenil SPECT with brain perfusion assessed using Tc-99m HMPAO SPECT.. Early and delayed I-123 iomazenil SPECT images acquired 20 and 180 minutes after injection were compared with Tc-99m HMPAO SPECT studies acquired 15 to 20 minutes after injection in five patients with Alzheimer's disease.. Visual analysis of I-123 iomazenil images showed more severe (n = 4) and extensive (n = 3) defects than did Tc-99m HMPAO. Semiquantitative analysis was performed by normalizing the uptake of Tc-99m HMPAO and I-123 iomazenil in individual brain regions in the cerebellum and expressing these values as a ratio of the occipital regions. The analysis of brain regional ratios in Tc-99m HMPAO studies showed a low but significant correlation with ratios of delayed (r = 0.325, P < 0.05) images in the I-123 iomazenil studies. Furthermore, when compared with Tc-99m HMPAO, early (P < 0.01) and delayed mean ratios (P < 0.05) were significantly less in the frontal regions; early mean ratios were significantly less in the temporal regions (P < 0.05), and delayed (P < 0.05) mean ratios were significantly less in the parietal regions.. Tc-99m HMPAO images were better correlated with I-123 iomazenil images, indicating cortical synaptic density (delayed images). I-123 iomazenil SPECT in patients with Alzheimer's disease provided more sensitive information than Tc-99m HMPAO, allowing evaluation of brain perfusion and synaptic density.

Topics: Alzheimer Disease; Brain; Female; Flumazenil; Humans; Iodine Radioisotopes; Male; Middle Aged; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Topics: Adolescent; Adult; Alzheimer Disease; Bipolar Disorder; Cerebral Cortex; Cerebrovascular Circulation; Depressive Disorder; Diagnosis, Differential; Female; Humans; Male; Radiopharmaceuticals; Substance-Related Disorders; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Thirty-four patients with a probable Alzheimer's Disease (AD) (mild AD = 16; moderate AD = 18) and 12 matched controls were evaluated using semiquantitative SPECT-99mTc-HMPAO and neuropsychological tests (CERAD).. Both temporal hypoperfusion (p < 0.01) and memory tests (p < 0.001) made it possible to differentiate the controls from mild AD patients. In these patients, significant correlations (p < 0.05) were also found between: 1) delayed recall test/temporal hypoperfusion, 2) learning memory test/temporoparietal and frontal hypoperfusion and 3) visual constructive praxis/posterior temporal hypoperfusion. In contrast to mild AD, moderate AD patients showed higher temporal (p < 0.01) parietal and frontal (p < 0.05) hypoperfusion along with worsening of praxis (p < 0.001) and memory tests (p < 0.05).. SPECT imaging and neuropsychology evaluation can distinguish controls from AD patients with mild an moderate grades of dementia, showing a strong correlation from the early stages of AD.

Topics: Aged; Alzheimer Disease; Brain; Cerebrovascular Circulation; Dementia; Diagnosis, Differential; Female; Humans; Male; Memory Disorders; Middle Aged; Neuropsychological Tests; Sensitivity and Specificity; Severity of Illness Index; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

In longitudinal brain studies of dementia of the Alzheimer type (DAT), the cerebellum is often used as a reference region for single photon emission computed tomography (SPECT) quantification, which assumes no significant regional influence of physiological fluctuations or pathology. With the use of absolute quantification in DAT patients, reproducibility of cerebellar uptake of technetium-99m-d,l-hexamethylpropyleneamine oxime (HMPAO) was tested and compared with the mean absolute cerebellar tracer uptake value in DAT patients and healthy control subjects. In 13 DAT patients SPECT studies were repeated within 2 weeks to assess reproducibility of cerebellar regional brain uptake (rBU). With calibrated point sources as scaling factors, cerebellar activity was expressed as rBU of HMPAO per cm3 brain tissue in percent of the injected lipophilic dose of 740 MBq (20 mCi). Also, mean cerebellar rBU in patients suffering from DAT was calculated and compared with a previously established database obtained in healthy volunteers. Repeated SPECT studies within a 2-week interval in clinically stable patients resulted in a mean rBU increase of 6.8 +/- 10.3% in the second SPECT study as compared with the first. A similar shift was previously reported in healthy volunteers. Mean cortical cerebellar rBU values in DAT patients and in the healthy reference population concurred, after cumulative corrections for body surface and for a mean brain volume of 1350 ml (obtained in healthy control subjects), showing respective mean values of 53.9 +/- 7.4 and of 52.0 +/- 7.3 x 10(-6) of the injected lipophilic dose 740 MBq (20 mCi) of HMPAO per cm3 of brain tissue. A unidirectional shift in mean absolute cerebellar uptake values occurs between repeat SPECT examinations in DAT patients similar to previous findings in a group of healthy volunteers. The origin of this phenomenon remains elusive but deserves further study with regard to SPECT (semi)quantification in DAT patients. Most interestingly, the presented findings suggest that with the use of HMPAO SPECT in DAT patients the cerebellum remains scintigraphically uninvolved.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cerebellum; Female; Humans; Male; Prospective Studies; Radiopharmaceuticals; Reference Values; Reproducibility of Results; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To provide the clinician with a guide to the clinical utility of 99mTc-HMPAO single photon emission computed tomography (SPECT) and to the interpretation of specific test results in the differential diagnosis of dementia.. Three hundred and sixty three patients with dementia were studied prospectively for a median three (range 1-6) years and classified into disease groups on the basis of established clinical criteria. The degree to which different patterns of cerebral blood flow (CBF) abnormality found on 99mTc-HMPAO SPECT imaging at the time of initial patient presentation modified clinical diagnoses was determined by calculating the likelihood ratios for pairwise disease group comparisons. The optimal clinical usage of 99mTc-HMPAO SPECT was determined by calculating the percentage of significant test results for each pairwise disease group comparison.. Bilateral posterior CBF abnormality was found to significantly increase the odds of a patient having Alzheimer's disease as opposed to vascular dementia or frontotemporal dementia. Bilateral anterior CBF abnormality significantly increased the odds of a patient having frontotemporal dementia as opposed to Alzheimer's disease, vascular dementia, or Lewy body disease. "Patchy" CBF changes significantly increased the odds of a patient having vascular dementia as opposed to Alzheimer's disease. Unilateral anterior, unilateral anterior plus unilateral posterior, and generalised CBF abnormality failed to contribute to the differentiation of any of these forms of dementia.. 99mTc-HMPAO SPECT was found to be most useful in distinguishing Alzheimer's disease from vascular dementia and fronto temporal dementia, and least useful in differentiating between Alzheimer's disease and Lewy body disease, and between vascular dementia, frontotemporal dementia, and progressive aphasia. It is suggested that CBF SPECT should be used selectively and as an adjunct to clinical evaluation and CT.

Topics: Aged; Alzheimer Disease; Aphasia, Primary Progressive; Dementia; Dementia, Vascular; Diagnosis, Differential; Female; Humans; Likelihood Functions; Male; Middle Aged; Odds Ratio; Parkinson Disease; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The purpose of this work was to determine whether certain pathological groups and other groups at risk for neurological damage exhibited distinctive patterns of regional cerebral blood flow (rCBF) abnormality.. HMPAO SPECT images obtained from six groups of subjects were compared with a normal cortical rCBF atlas, based on multivariate, voxel-by-voxel methods. In each case, a significance image was outputted, highlighting voxels with deficits of > or =3 s.d. of normal. Abnormal patterns were examined for the six groups, which comprised a further 40 normal volunteers, 18 diver controls, 50 divers with decompression illness (DCI), 34 boxers, 23 schizophrenics and 21 subjects with Alzheimer's disease.. The percentages of abnormal cortical voxels for each group were 0.41%, 0.53%, 1.38%, 1.05%, 0.56% and 2.24%, respectively. The percentages of images in each group with at least one lesion of 10 or more connected abnormal voxels and at least 10 lesions of two or more connected voxels, respectively, were 8% and 8% (normal volunteers), 17% and 11% (diver controls), 38% and 38% (divers with DCI), 41% and 29% (boxers), 26% and 13% (schizophrenics) and 90% and 48% (subjects with Alzheimer's disease). This suggests that multiple small lesions are as common as single large lesions for divers with DCI but not for patients with Alzheimer's disease or schizophrenia. Large lesions are located predominantly in the parietal and inferior temporal regions for Alzheimer's disease, in the parietal and occipital regions for divers with DCI and boxers and in the inferior frontal region for schizophrenia.. It appears that the groups considered here do have different rCBF patterns and that the significance image is a useful way of demonstrating this fact.

Topics: Adult; Aged; Alzheimer Disease; Boxing; Brain; Case-Control Studies; Cerebrovascular Circulation; Decompression Sickness; Diving; Female; Humans; Image Processing, Computer-Assisted; Male; Radiopharmaceuticals; Reference Values; Risk Factors; Schizophrenia; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Topics: Alzheimer Disease; Brain; Humans; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Topics: Alzheimer Disease; Flumazenil; Humans; Iodine Radioisotopes; Radiopharmaceuticals; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Thirty-nine elderly depressed patients as well as 15 demented patients with Alzheimer's disease and 11 healthy volunteers were imaged at rest with a high resolution single-slice 12-detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-Exametazime (HM-PAO). Statistical parametric maps were computed to compare early- and late-onset depressed, Alzheimer patients and healthy volunteers and to examine associations between regional perfusion and clinical and MRI variables. Patients with late-onset depression showed reductions in temporal lobe perfusion compared with early-onset depression and controls. Alzheimer patients had the expected reduced perfusion in temporoparietal and prefontal cortex, as well as basal ganglia, compared with healthy controls. Compared with depressed patients, they showed a relative reduction in temporoparietal cortex, only. This difference was more pronounced between Alzheimer patients and early onset, compared to late-onset patients with depression. Periventricular white matter changes on MRI were associated with temporal lobe reductions of tracer uptake in depression. In the Alzheimer group, deep white matter MRI changes were associated with frontal perfusion deficits. Our results support a vulnerability hypothesis, which predicts that patients with late-onset depression will show more brain changes than patients with an early onset of their illness. Statistical parametric mapping in patients with organic psychiatric brain syndromes is feasible and promising as a clinical and research method.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Basal Ganglia; Brain; Brain Mapping; Cerebral Cortex; Depressive Disorder, Major; Diagnosis, Differential; Dominance, Cerebral; Feasibility Studies; Humans; Image Processing, Computer-Assisted; Mathematical Computing; Middle Aged; Reference Values; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

In mild Alzheimer's disease, SPECT imaging of regional cerebral blood flow has highlighted deficits in the posterior association cortex, and later in the disease process, the deficit spreads to involve the frontal cortex. The sigma4 allele of apolipoprotein E is a risk factor for Alzheimer's disease. The effect of apolipoprotein E polymorphism on cerebral perfusion was studied. The hypothesis was that those patients with Alzheimer's disease who carry the sigma4 allele would have more severe cerebral hypoperfusion.. Thirty one patients with Alzheimer's disease and eight age and sex matched control subjects were examined in a three year longitudinal study. Patients with Alzheimer's disease were divided into subgroups according to their number of sigma4 alleles. Regional cerebral blood flow ratios referred to the cerebellum were examined by 99mTc-HMPAO SPECT. Apolipoprotein E genotypes were determined by digestion of polymerase chain reaction products with the restriction enzyme Hha1.. All patients with Alzheimer's disease had bilateral temporoparietal hypoperfusion compared with control subjects. The two sigma4 allele subgroups had the lowest ratios at the baseline assessment in the parietal and occipital cortices, and at the follow up in the temporal, parietal, and occipital cortices. They had the highest reduction in percentage terms in the temporal and occipital cortices compared with the other subgroups. However, the global clinical severity did not differ at the baseline or follow up examinations between the subgroups.. Apolipoprotein E polymorphism is involved in the pathogenesis and heterogeneity of Alzheimer's disease as the most severe cerebral hypoperfusion was found in the sigma4 allele subgroups. This might have implications for therapeutic approaches in Alzheimer's disease.

Topics: Aged; Alleles; Alzheimer Disease; Apolipoproteins E; Brain; Female; Follow-Up Studies; Genotype; Humans; Longitudinal Studies; Male; Polymerase Chain Reaction; Polymorphism, Genetic; Radiopharmaceuticals; Regional Blood Flow; Severity of Illness Index; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The purpose of this study was to compute and compare the group mean HMPAO brain SPECT images of patients with senile dementia of Alzheimer's type (SDAT) and age matched control subjects after transformation of the individual images to a standard size and shape.. Ten patients with Alzheimer's disease (age 71.6 +/- 5.0 yr) and ten age matched normal subjects (age 71.0 +/- 6.1 yr) participated in this study. Tc-99m HMPAO brain SPECT and X-ray CT scans were acquired for each subject. SPECT images were normalized to an average activity of 100 counts/pixel. Individual brain images were transformed to a standard size and shape with the help of Automated Image Registration (AIR). Realigned brain SPECT images of both groups were used to generate mean and standard deviation images by arithmetic operations on voxel based numerical values. Mean images of both groups were compared by applying the unpaired t-test on a voxel by voxel basis to generate three dimensional T-maps. X-ray CT images of individual subjects were evaluated by means of a computer program for brain atrophy.. A significant decrease in relative radioisotope (RI) uptake was present in the bilateral superior and inferior parietal lobules (p < 0.05), bilateral inferior temporal gyri, and the bilateral superior and middle frontal gyri (p < 0.001). The mean brain atrophy indices for patients and normal subjects were 0.853 +/- 0.042 and 0.933 +/- 0.017 respectively, the difference being statistically significant (p < 0.001).. The use of a brain image standardization procedure increases the accuracy of voxel based group comparisons. Thus, intersubject averaging enhances the capacity for detection of abnormalities in functional brain images by minimizing the influence of individual variation.

Topics: Aged; Alzheimer Disease; Automation; Brain; Cerebrovascular Circulation; Humans; Image Processing, Computer-Assisted; Radiopharmaceuticals; Reference Values; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Cerebral SPECT imaging has the potential to make important contributions in the follow-up care of patients with Alzheimer's disease. An unusual case of a patient who showed a follow-up cerebral blood flow pattern different from that routinely seen in Alzheimer's disease patients is reported here. Qualitative and voxel-based objective evaluation of follow-up scans revealed improvement in parietotemporal deficits that had been observed on a baseline study. This change was observed without significant further deterioration in ratings by dementia batteries. This case shows that a baseline regional cerebral blood flow study might be necessary for reference and comparison in the proper follow-up care of Alzheimer's disease patients.

Topics: Aged; Alzheimer Disease; Brain; Cerebrovascular Circulation; Humans; Male; Mental Status Schedule; Nootropic Agents; Pyrrolidinones; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The discrepancy between 99mTc-hexamethyl-propyleneamine oxime (HMPAO) and 99mTc-ethyl cysteinate dimer (ECD) in Alzheimer's disease (AD) was investigated and compared with in cerebral ischemic disease (CID). The subjects were fourteen AD and thirty-one CID patients with clinically reasonable rCBF reduced lesion on 133Xe SPECT. The subjects did not include the cases of acute and subacute CID. These SPECT were performed within two weeks by ring-type dynamic SPECT (HEADTOME, Shimadzu, Japan). In the CID group, both of HMPAO and ECD SPECT could hardly detect the mildly reduced rCBF lesion on 133Xe SPECT but normal on X-CT. In the case of AD group, the rCBF-reduced lesion on 133Xe SPECT could be detected well by ECD SPECT, but the HMPAO hardly detected the reduced lesion. This discrepancy between HMPAO and ECD may be due to the difference of the retention mechanism. In the case of AD, the injury of esterase activity that participates with the ECD retention may be more notable than that of glutathione activity for the HMPAO retention. These results suggest suggest that the reduction of ECD or HMPAO density depends directly on the insufficiency of retention mechanism rather the than rCBF reduction. And the insufficiency of this retention mechanism depends on also type of the disease i.e. AD or CID.

Topics: Alzheimer Disease; Brain; Cerebrovascular Circulation; Cysteine; Esterases; Glutathione; Humans; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Xenon Radioisotopes

To evaluate single photon emission computed tomographic (SPECT) imaging of regional cerebral blood flow in the diagnosis of Alzheimer disease (AD) and the differential diagnosis of the dementias.. Regional cerebral blood flow SPECT was performed with inhaled xenon-133 in 261 patients and with injected technetium-99m hexamethyl-propyleneamine oxime (HMPAO) in 162 patients with possible dementia. In 16 patients, both agents were used in 1 day. SPECT images obtained in elderly healthy control subjects (with Xe-133 in 15, with Tc-99m HMPAO in 14) were available. In each patient without AD, further classification of disease was attempted. Histopathologic correlation was available in 54 patients (with autopsy in 51, with biopsy in three).. SPECT diagnoses were true-positive in 37, true-negative in eight, false-positive in three, and false-negative in six patients. Sensitivity was 86% (37 of 43; 95% confidence limits = .72, .95); specificity, 73% (eight of 11; confidence limits = .39, .94); positive predictive value, 92% (37 of 40; confidence limits = .80, .98); and negative predictive value, 57% (eight of 14; confidence limits = .29, .82).. Regional cerebral blood flow SPECT may assist in the early and late diagnoses of AD and in the differential-diagnosis of the dementias when there is a complicated or confusing clinical picture.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Cerebrovascular Circulation; Dementia; Diagnosis, Differential; False Negative Reactions; False Positive Reactions; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Predictive Value of Tests; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Xenon Radioisotopes

This study was designed to elucidate a central type of benzodiazepine (Bz) receptor distribution in patients with Alzheimer's disease using SPECT with [123I]iomazenil (IMZ).. Eight patients with probable Alzheimer's disease were studied. Benzodiazepine receptor imaging was performed 15 min (early) and 180 min (delayed) after intravenous administration of 167 MBq IMZ, sequentially, using hexamethylpropylene amine oxime (HMPAO) SPECT to evaluate regional cerebral perfusion.. Early IMZ-SPECT depicted areas of reduced uptake in sites of decreased cerebral blood flow (CBF), but each area of decreased uptake was extended wider than the area of hypoperfusion. Delayed IMZ-SPECT images demonstrated a similar pattern of decreased area of CBF; the affected region in Bz receptor bindings, however, was clearer and broader compared with that in either HMPAO-SPECT or early IMZ-SPECT. In comparison with the uptakes for the normal cerebral hemisphere (ratio to the contralateral cerebellum) in patients with unilateral cerebral infarction as a control group (n = 4), the patients with Alzheimer's disease showed distinctive bilateral frontal or parietal defects (p < 0.05).. Brain SPECT using IMZ may be more sensitive than CBF images in patients with Alzheimer's disease.

Topics: Alzheimer Disease; Brain; Female; Flumazenil; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tissue Distribution; Tomography, Emission-Computed, Single-Photon

Research suggests an association between frontal and temporal injury and antisocial conduct. We studied the frequency of antisocial behaviours in fronto-temporal dementia (FTD) where pathology is anterior frontal-temporal, compared with Alzheimer's disease (AD) where pathology is primarily posterior temporal-parietal.. The presence of antisocial conduct was compared in 22 FTD versus 22 AD subjects. All FTD patients had anterior frontal or temporal hypoperfusion with single photon emission computed tomography, whereas those with AD had posterior temporal-parietal hypoperfusion.. Ten FTD and one AD subject showed antisocial behaviours, which included assault, indecent exposure, shoplifting and hit-and-run driving. Three FTD subjects were arrested. This difference was highly significant (P = 0.004).. Degeneration of frontal and temporal lobes predisposes to antisocial behaviour. This study supports a relationship between frontal-temporal dysfunction and certain types of antisocial activities.

Topics: Aggression; Alzheimer Disease; Antisocial Personality Disorder; Dementia; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Xenon Radioisotopes

Dementia of the Alzheimer-type (DAT) is characterized by progressive cognitive decline, variably combined with frontal lobe release signs, parkinsonian symptoms and myoclonus. The features of diffuse Lewy body disease (DLBD), the second most common cause of degenerative dementia, include progressive cognitive deterioration, often associated with levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, psychotic symptoms (visual and auditory hallucinations, depression), hypersensitivity to neuroleptics and orthostatic hypotension. A recent report suggests that positron emission tomography studies in patients with degenerative dementia may be useful in the differential diagnosis of DAT and DLBD. However, the diagnostic role of single-photon emission tomography (SPET) studies remains to be established. The aim of this study was therefore to evaluate regional cerebral perfusion [with either technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or 99mTc-ethyl cysteinate dimer (99mTc-ECD) SPET] and striatal dopamine transporter density [using iodine-123 2 beta-carboxymethoxy-3 beta-[4-iodophenyl]tropane (123I-beta-CIT) SPET] in patients with DAT and DLBD. Six patients with probable DAT and seven patients with probable DLBD were studied. Blinded qualitative assessment by four independent raters of 99mTc-HMPAO or 99mTc-ECD SPET studies revealed bilateral temporal and/or parietal hypoperfusion in all DAT patients. There was additional frontal hypoperfusion in two patients and occipital hypoperfusion in one patient. In the DLBD group, regional cerebral perfusion had a different pattern. In addition to temporoparietal hypoperfusion there was occipital hypoperfusion resembling a horseshoe defect in six of seven patients. In the DAT group, the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was 2.5 +/- 0.4, with an increase to 5.5 +/- 1.1 18 h after tracer injection. In comparison, in the DLBD patients the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was significantly reduced to 1.7 +/- 0.3, with a modest increase to 2.1 +/- 0.4 18 h after tracer injection (P < 0.05, Scheffe test, ANOVA). These results suggest that 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT SPET may contribute to the differential diagnosis between DAT and DLBD, showing different perfusion patterns and more severe impairment of dopamine transporter function in DLBD than in DAT.

Topics: Aged; Alzheimer Disease; Brain; Carrier Proteins; Case-Control Studies; Cocaine; Cysteine; Dementia; Diagnosis, Differential; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Organotechnetium Compounds; Oximes; Parkinson Disease; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

In this study, we assessed the accuracy and reliability of MRI-guided SPECT measurements of medial temporal lobe blood flow in Alzheimer's disease (AD).. Interactively aligned three-dimensional MP-RAGE MRI and 99mTc-HMPAO SPECT images were used for MRI-guided measurement of medial temporal lobe CBF in eight control subjects and eight patients with probable AD. Intraoperator reliability was assessed by repeated alignment and measurement by one experienced operator. Accuracy was assessed by examining two subjects with fiducial markers.. The alignment error was less than 1 SPECT pixel size (3.5 mm) and the coefficient of variation in repeated measures of medial temporal-to-cerebellar CBF ratios was 3.2%. The difference in mean medial temporal-to-cerebellar CBF ratios between eight control subjects and eight AD patients was 12%. Also by using three-dimensional seed-grow defined healthy brain reference regions, there were significant differences between control subjects and AD patients in medial temporal blood flow. Furthermore, the volumes of the MRI-defined medial temporal ROIs were smaller in the AD patients. The best separation between AD patients and control subjects was achieved by combining MRI measurements of atrophy and SPECT measurements of CBF.. These data show that the accuracy and reliability of MRI-guided SPECT measurements of medial temporal CBF clearly allow the detection of changes in AD. Also, a direct comparison of structural and functional changes is possible by this methodology, which might improve the early diagnosis of AD.

Topics: Alzheimer Disease; Case-Control Studies; Cerebrovascular Circulation; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Organotechnetium Compounds; Oximes; Reproducibility of Results; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

Dementia of the Alzheimer's type [(S)DAT] and dementia with frontal features (FLD) are nosological entities with different prognoses and presumed pathophysiology. There is a need for noninvasive differential diagnostic tools. To evaluate whether SPECT perfusion imaging could discriminate between these neurodegenerative disorders, we performed a comparative study.. SPECT scans using 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) of 21 patients with FLD were compared with those obtained in a group of 19 age- and severity-matched patients suffering from (S)DAT. Brain SPECT perfusion deficits were scored by visual qualitative analysis with respect to location, lateralization and severity. A total severity score of cerebral hypoperfusion (maximal value = 18) was calculated by adding all severity scores (scored between 0 and 3; 0 = no perfusion deficit; 1 = 13%-30% hypoperfusion; 2 = 30%-50%, hypoperfusion and 3 = > 50% hypoperfusion including breaching of the cortex) for right and left frontal, parietal and temporal lobes. Moreover, bifrontal hypoperfusion (Fa) was scored, yielding a value between 0 and 6 by adding the two frontal severity scores.. No significant correlation was found between MMSE scores and total severity scores on SPECT. A statistically significant correlation was found between the Middelheim frontality score and frontal severity score. Statistically more significant bilateral hypoperfusion of the parietal lobes was found in the (S)DAT group. Conversely, bifrontal hypoperfusion was found more in the FLD group. Stepwise logistic regression analysis identified the severity of bifrontal hypoperfusion as the most significant contributing parameter to correctly classifying (S)DAT versus FLD on SPECT. The probability of predicting (S)DAT based on the SPECT scan is calculated with the following formula: [equation: see text] Using this equation, a value above 0.5 was predictive for (S)DAT and a calculated value under 0.5 was predictive for FLD. Using this model, 81% of the FLD group and 74% of the (S)DAT were correctly classified.. Technetium-99m-HMPAO SPECT may help in discriminating FLD from (S)DAT. Bifrontal hypoperfusion was found to be the most powerful predictor of clinical classification. Further validation of the presented logistic regression model is warranted.

Topics: Aged; Alzheimer Disease; Brain; Cerebrovascular Circulation; Dementia; Diagnosis, Differential; Female; Humans; Logistic Models; Male; Organotechnetium Compounds; Oximes; Predictive Value of Tests; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The objective of this study was to assess the diagnostic value for Alzheimer disease (AD) of single-photon-emission computed tomography (SPECT) and magnetic resonance imaging (MRI), separately and in combination. The study was part of a two-stage population-based study of mental functioning among noninstitutionalized 65-to 85-year-olds living in Amsterdam, The Netherlands. Participants (n = 51) were randomly selected within strata of cognitive function to obtain a sample of AD patients (n = 10) and clinically normal subjects (n = 41), of whom 22 displayed some cognitive impairment and fulfilled criteria for "minimal dementia" according to the Cambridge Examination for Mental Disorders of the Elderly. Coronal T1-weighted MRI was used to visualize the medial temporal lobe. Medial temporal lobe atrophy (MTA) was assessed qualitatively on a 0-4 scale. Regional cerebral blood flow on SPECT was assessed with the use of technetium 99m-HMPAO in three manually drawn regions of interest (frontal, parietal, and temporoparietal). Ratios were calculated by using the cerebellum as the reference area. MTA differed significantly between AD patients and clinically normal subjects (p = 0.0009), with sensitivity for AD of 70% and a specificity of 76%. None of the three SPECT ratios differed between normal and AD subjects. The temporoparietal/cerebellar ratio had a sensitivity of 30% and a specificity of 71% as a cutoff of 0.76. When both tests were positive the combined sensitivity was low (20%), but the false-positive rate was also very low (5%). A negative result on MRI or any SPECT ratio yielded a high specificity (93%-98%) but also a high false-negative rate (60-80%). Adding SPECT to MRI seems useful only if a diagnosis of AD is suspected clinically and confirmation is needed. When the clinical probability that AD is absent is high, normal results on either MRI or SPECT may confirm this notion. Given the fact that structural imaging should be performed in a clinical workup for dementia, using MRI only would be the most cost-effective approach.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Female; Humans; Magnetic Resonance Imaging; Male; Organotechnetium Compounds; Oximes; Predictive Value of Tests; Residence Characteristics; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To examine neurological, neuropsychological, psychiatric, and cerebral perfusion correlates of leukoaraiosis in Alzheimer's disease.. A consecutive series of patients with probable Alzheimer's disease was assessed with a comprehensive neuropsychological battery, a structured psychiatric evaluation, the unified Parkinson's disease rating scale, MRI, and single photon emission computed tomography with technetium 99m hexamethylpropyleneamine oxime (HMPAO) and regional cerebral perfusion measurements.. Patients with Alzheimer's disease and leukoaraiosis were significantly more apathetic and had significantly more extrapyramidal signs than patients with Alzheimer's disease without leukoaraiosis. Patients with Alzheimer's disease with leukoaraiosis also had significantly lower bilateral perfusion in the basal ganglia, thalamus, and frontal lobes than patients with Alzheimer's disease without leukoaraiosis. On the other hand, there were no significant differences between groups in age, duration of illness, depression scores, severity of delusions, or deficits on specific neuropsychological tasks.. Leukoaraiosis in Alzheimer's disease may produce significant basal ganglia, and thalamic and frontal lobe dysfunction, which may be associated with more severe apathy and extrapyramidal signs.

Topics: Aged; Alzheimer Disease; Analysis of Variance; Basal Ganglia Diseases; Brain; Brain Diseases; Cerebrovascular Circulation; Female; Humans; Magnetic Resonance Imaging; Male; Neurologic Examination; Neuropsychological Tests; Organotechnetium Compounds; Oximes; Psychiatric Status Rating Scales; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The purpose of this study was to investigate the ability of patients with Alzheimer's disease to shift attention between spatial locations and between objects, and to examine the brain regions involved in these cognitive operations using single photon emission computed tomography (SPECT) imaging. A recent study of patients with focal lesions provided evidence that the right and left parietal lobes are differentially involved in shifting selective attention from invalidly cued spatial locations and objects, respectively (Egly et al. J Exp Psychol Gen 1994; 123: 161-77). Accordingly, in Alzheimer's disease patients, we hypothesized that right parietal hypoperfusion on SPECT would be associated with deficits on the spatial-based component of a cued reaction time task, and left parietal hypoperfusion would be associated with the deficits on the object-based component. Attentional performance of Alzheimer's disease patients (n = 29) was compared with aged-matched normal controls (n = 17) using a cued reaction time task based on Egly et. al. (1994). Regions of interest were defined semi-automatically on SPECT, and were anatomically localized with the aid of co-registered MRI. As hypothesized, in Alzheimer's disease patients, reaction time costs of invalid targets eliciting shifts of attention between spatial locations were selectively correlated with SPECT hypoperfusion in the right superior parietal lobe; while reaction time costs of between-object shifts of attention were correlated with hypoperfusion in the left inferior parietal lobe. These results provide evidence for the specialized roles of the right and left parietal regions in the spatial and object components of attentional shifting respectively, and suggest that the cognitive profile associated with Alzheimer's disease includes both spatial- and object-based attentional impairments.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Attention; Brain Mapping; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Organotechnetium Compounds; Oximes; Parietal Lobe; Reaction Time; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The purpose of this study was to investigate patterns of 99mTc-HMPAO single-photon emission computed tomography (SPECT) abnormality in Lewy body disease (LBD) and to compare findings with those encountered in Alzheimer's disease (AD). The study group comprised 20 consecutive patient referrals fulfilling clinical criteria for LBD. All patients had fluctuating cognitive impairment and 'subcortical' dysfunction with or without perceptuospatial and/or linguistic impairment. Six patients had asymmetrical signs of parkinsonism (three left-sided and three right-sided), and 14 patients had symmetrical features of extrapyramidal involvement. 99mTc-HMPAO SPECT imaging was performed on LBD patients and findings compared with those of 57 patients with 'probable' AD and 11 normal age-matched controls. Within the LBD and AD groups, patterns of cortical and subcortical blood-flow abnormality were compared with patterns of cognitive and neurological breakdown. LBD was associated with bilateral posterior cortical blood flow abnormality, a pattern strikingly similar to that found in AD. Within the LBD group, cortical blood-flow abnormality was found to reflect patterns of neurological dysfunction (parkinsonism) indicative of subcortical involvement. In contrast, cortical blood-flow changes did not reflect patterns of neuropsychological impairment suggestive of cortical dysfunction. Within the AD group, cortical blood-flow changes were mirrored by the pattern of neuropsychological impairment. Findings support the notion that cortical blood-flow abnormality in LBD might reflect a combination of direct cortical pathology and cortical deafferentation secondary to subcortical Lewy body pathology. It would appear that 99mTc-HMPAO SPECT imaging is of limited value in the clinical differentiation of LBD and AD.

Topics: Aged; Alzheimer Disease; Analysis of Variance; Case-Control Studies; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Parkinson Disease; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The authors studied 33 normal patients who ranged in age from 8 to 71 years to establish a normative data base for young-age, middle-age, and older-age subjects using a computer automated semi-quantitative cortical annular region of interest (ROI) method. The data were grouped to obtain a "young age-range" normative data base of mean age +/- 1 S.D. = 13.1 +/- 4.8 years (seven subjects with an age range of 6 to 20 years); a "middle age-range" normative data base of mean age +/- 1 S.D. = 39 +/- 2.7 years (12 subjects with an age range of 35 to 43 years); and an "older age-range" normative data base of mean age +/- 1 S.D. = 59.7 +/- 5.8 years (14 subjects with an age range of 55 to 71 years). Normative values were obtained for brain level parallel to and positioned at 3.5, 5.5, and 7.5 cm above the canthomeatal (CM) line. The results show that the average global rCBF indices (defined as cortical/cerebellar ratios) for the young age-range group were 0.98, 0.99, 1.07; middle age-range group were 0.84, 0.86, and 0.88; and older age-range group were 0.86, 0.87 and 0.87 for CM + 3.5 cm, CM + 5.5 cm, and CM + 7.5 cm, respectively. In routine clinical studies, on more then 2,000 Tc-99m HMPAO brain SPECT scans, the authors have employed this semi-quantitative cortical circumferential normalization method of analysis to accurately calculate indices representing cortical blood flow values. This method also allows efficient comparison of individual patient values to age-range matched normal control groups to assist in disease diagnosis.

Topics: Adolescent; Adult; Aged; Aging; Alzheimer Disease; Brain Diseases; Case-Control Studies; Cerebellum; Cerebral Cortex; Cerebrovascular Circulation; Child; Corpus Callosum; Frontal Lobe; Gyrus Cinguli; Humans; Image Processing, Computer-Assisted; Middle Aged; Parietal Lobe; Radiopharmaceuticals; Reference Values; Reproducibility of Results; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Alzheimer's disease is the most frequent cause of degenerative dementia. Despite the available diagnostic criteria, improvement of diagnosic accuracy is still required. The aim of this prospective study was to assess in a large population of patients referred to a memory clinic the diagnostic value of the combination of medial temporal lobe atrophy on temporal oriented CT and decreased temporoparietal uptake on HMPAO single photon emission tomography (SPECT).. The study was conducted in 125 patients aged 51-93: 64 with probable Alzheimer's disease (Mean (SD) mini mental state examination (MMSE)=18.34 (6.93)), duration of disease=6.48 (2.93) years, 13 possible Alzheimer's disease (MMSE=21.58 (5.48), duration of disease=6.08 (2.56)), 48 patients with miscellaneous memory disorders (MMSE=21.98 (6.10), duration the disease = 6.85 (3.91)).. For the diagnosis of probable Alzheimer's disease, the sensitivity of this association was 0.56, the specificity 0.93, the positive predictive value 0.95, and the negative predictive value 0.45. The diagnosic accuracy was 0.68. Both medial temporal atrophy and parietotemporal decrease in uptake were present in four of 13 patients with possible Alzheimer's disease and 11 of 48 with miscellaneous memory disorders. The association was absent in 27 of 29 patients with frontotemporal dementia. In mild stages (MMSE>18; n = 32), the sensitivity of the association was 0.34, the specificity 0.93, the positive predictive value 0.85, and the negative predictive value 0.57. The diagnosic accuracy was 0.53.. This association, although not sensitive, helps to select patients with high probability of Alzheimer's disease at an early stage which can be of interest for clinical and research purposes.

Topics: Aged; Alzheimer Disease; Atrophy; Cognition Disorders; Dementia; Female; Frontal Lobe; Humans; Male; Neuropsychological Tests; Parietal Lobe; Predictive Value of Tests; Retrospective Studies; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

The purpose of this study was to analyse the frequency of the different pathological perfusion patterns in SPECT in a clinical, unselected population of patients with Alzheimer's disease. In 91 patients and 16 control subjects regional cerebral blood flow (rCBF) was measured with Single Photon Emission Computed Tomography (SPECT) using 99mTc-hexa-methyl-propyleneamine oxime (HMPAO). 95% confidence intervals obtained from the perfusion values of the control subjects were used to define normal perfusion ranges. The frequency of perfusion deficits in the left frontal, temporal, parietal and occipital lobes were 62.2%, 60.4%. 70.3% and 23.1%, respectively. In the right hemisphere the corresponding values were 60.4%, 58.2%, 63.7% and 9.9%. With the exception of the occipital lobes these frequencies were not significantly different. The analysis of the perfusion pattern of each patient revealed 35 different combinations of lobes with perfusion deficits. The temporo-parietal perfusion deficits were not more frequent than the temporofrontal perfusion deficits. These results suggest that in the clinical routine a high variety of heterogeneous rCBF patterns have to be expected.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Case-Control Studies; Cerebrovascular Disorders; Cognition Disorders; Female; Follow-Up Studies; Humans; Male; Middle Aged; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

In a prospective study of more than 200 cases of dementia and 119 controls, annual technetium-99m-hexamethyl-propylene amineoxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) and annual medial temporal lobe (MTL) oriented X-ray computed tomography (CT) have been used to evaluate the diagnostic potential of functional and structural neuroimaging in the differential diagnosis of dementia. Some subjects have had up to 7 annual evaluations. So far, of 151 who have died, 143 (95%) have come to necropsy. Histology is known for 118, of whom 80 had Alzheimer's disease (AD), 24 had other "non-AD" dementias, and 14 controls with no cognitive deficit in life also had no significant central nervous system pathology. To compare the findings in the dementias with the profile of structural and functional imaging in the cognitively normal elderly, scan data from 105 living, elderly controls without cognitive deficit have also been included in the analysis. All clinical diagnoses were according to National Institute of Neurological and Communicable Disease and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; DSM-III-R) criteria, and all histopathological diagnoses according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. Early data from this cohort have suggested that the combination of both MTL atrophy seen on CT with parietotemporal hypoperfusion on SPECT may predict the pathology of AD. The diagnostic sensitivity, specificity, accuracy, and positive and negative predictive values of the NINCDS-ADRDA and DSM-III-R criteria could be assessed in this cohort against the gold standard of histopathology. The diagnostic potential of CT evidence of MTL atrophy alone, SPECT evidence of parietotemporal hypoperfusion alone, and the combination of both of these scan changes in the same individual could then be compared against the diagnostic accuracy of clinical operational criteria in the pathologically confirmed cases. Furthermore, all of these modalities could be compared with the diagnostic accuracy of apolipoprotein E4 (Apo E4) genotyping to predict AD in the histopathologically confirmed cohort. In this population, NINCDS "probable-AD" was 100% specific, 49% sensitive, and 66% accurate; "possible-AD" was only 61% specific, but 93% sensitive and 77% accurate; and the combination of both "probable-AD" and "possible-AD"

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Apolipoproteins E; Atrophy; Cognition Disorders; Dementia; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Parietal Lobe; Predictive Value of Tests; Psychiatric Status Rating Scales; Radiopharmaceuticals; Severity of Illness Index; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

To better understand how to differentiate the "in vivo" normal aging brain from pathological conditions, namely dementia of the Alzheimer type (DAT), by means of magnetic resonance imaging (MRI), single photon emission computerized tomography (SPECT), and proton magnetic resonance spectroscopy (1H-MRS), to show neuroanatomical, perfusional and neurochemical details, respectively.. 1H-MRS, MRI-based hippocampal volumetry and 99mTc-HMPAO SPECT were performed in healthy older subjects as well as patients suffering from age-associated memory impairment (AAMI) and dementia of Alzheimer type (DAT).. Eighteen subjects were selected from those referred to an outpatient clinic for diagnostic evaluation of cognitive impairment entered the study. Six patients fulfilled NINCDS-ADRDA diagnostic criteria for DAT, six subjects were affected by AAMI, and six cognitively healthy subjects, selected from among relatives of the patients, were defined as controls.. The 1H-MRS and MRI studies were performed on a 1.5 Tesla NMR-imaging system equipped with a spectroscopy research package. SPECT scans were performed on a Gamma 11 computer system.. 1H-MRS showed significantly lower N-acetylasparatate concentration in DAT and AAMI compared with controls. Conversely, mean inositol concentration was significantly higher in DAT than in controls, whereas AAMI subjects registered intermediate values. MRI measurements showed significantly reduced volumes of hippocampal formations in DAT and AAMI groups compared with controls. Finally, 99mTc-HMPAO SPECT showed a significant frontal, temporo-parietal, and occipital hypoperfusion in DAT patients only.. These findings support the hypothesis of a continuum among the three conditions studied, or at least between AAMI and DAT, where AAMI seems to be an early, monosymptomatic stage of Alzheimer disease. Accepting this view, it would be questionable to maintain the term "age-associated memory impairment" as a discrete entity.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Aspartic Acid; Brain Chemistry; Case-Control Studies; Diagnosis, Differential; Female; Hippocampus; Humans; Inositol; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Memory Disorders; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Psychiatric, neuropsychological, and cerebral blood flow differences between patients with ischemic vascular dementia (IVD) or Alzheimer's disease (AD) were examined.. A consecutive series of patients who met either the criteria of the National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association for probable AD or the State of California AD Diagnostic and Treatment Centers criteria for probable IVD were included in the study. Twenty consecutive patients with IVD were matched for age, sex, and Mini-Mental State Examination scores with 40 consecutive patients with probable AD. Patients underwent a psychiatric interview, a neuropsychological assessment, and single-photon emission CT imaging with 99mTc-hexamethylpropyleneamine oxime.. Patients with IVD showed significantly more severe anosognosia (P<.05) and emotional lability (P<.01) than AD patients, but no significant between-group differences were found in the frequency and severity of depression. IVD patients showed significantly more severe deficits in tests of planning, sequencing (P<.05), and verbal fluency (P<.05) as well as significantly more severe cerebral blood flow deficits in the basal ganglia (P<.01) and the frontal lobes (P<.001) than AD patients.. Patients with IVD showed a relatively more severe dysfunction of the frontal lobes as demonstrated by single-photon emission CT and expressed in specific psychiatric and neuropsychological changes than AD patients matched for age, sex, and severity of dementia.

Topics: Aged; Alzheimer Disease; Basal Ganglia; Brain Ischemia; Case-Control Studies; Cerebrovascular Circulation; Cognition Disorders; Dementia, Vascular; Depression; Emotions; Female; Frontal Lobe; Humans; Interview, Psychological; Male; Mental Health; Neuropsychological Tests; Neuropsychology; Organotechnetium Compounds; Oximes; Self Concept; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Verbal Behavior

The value of functional and morphological neuroimaging in the early diagnosis of Alzheimer's disease (AD) is still debated. Described here are cerebral perfusion and linear measures of medial temporal lobe atrophy in 2 monozygotic twins discordant for AD who were investigated with technetium 99m-hexamethylpropy-leneamineoxime single-photon emission tomography (SPET) and magnetic resonance (MR) imaging. Both showed pathological cortical perfusion findings on SPET, while medical temporal lobe atrophy was present only in the affected twin. MR measures of medial temporal lobe atrophy have greater agreement with clinical data than do SPET measures of cerebral perfusion. Evaluation of atrophy may be useful in the early diagnosis of AD.

Topics: Activities of Daily Living; Alzheimer Disease; Atrophy; Cerebrovascular Circulation; Diseases in Twins; Electroencephalography; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon; Twins, Monozygotic

The usefulness of artificial neural networks in the classification of 99mTc-HMPAO SPECT axial brain scans was investigated in a study group of Alzheimer's disease patients and age-matched normal subjects.. The cortical circumferential profiling (CCP) technique was used to extract information regarding patterns of cortical perfusion. Traditional analysis of the CCP data, taken from slices at the level of the basal ganglia, indicated significant perfusion deficits for Alzheimer's disease patients relative to normals, particularly in the left temporo-parietal and left posterior frontal areas of the cortex. The compressed profiles were then used to train a neural-network classifier, the performance of which was compared with that of a number of more traditional statistical (discriminant function) techniques and that of two expert viewers.. The optimal classification performance of the neural network (ROC area = 0.91) was better than that of the alternative statistical techniques (max. ROC area = 0.85) and that of the expert viewers (max. ROC area = 0.79).. The CCP produces perfusion profiles which are well suited to automated classification methods, particularly those employing neural networks. The technique has the potential for wide application.

Topics: Aged; Alzheimer Disease; Brain; Case-Control Studies; Cerebrovascular Circulation; Discriminant Analysis; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Neural Networks, Computer; Organotechnetium Compounds; Oximes; ROC Curve; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

SPECT has shown increasing promise as a diagnostic tool in Alzheimer's disease (AD). Recently, a new SPECT brain perfusion agent, 99mTc-ethyl cysteinate dimer (99mTc-ECD) has emerged with purported advantages in image quality over the established tracer, 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO). This research aimed to compare cerebral images for 99mTc-HMPAO and 99mTc-ECD in discriminating patients with AD from control subjects.. Twenty-four AD patients (mean age +/- s.d. = 68.9 +/- 8.2 yr) and 13 healthy subjects (68.4 +/- 8.0 yr) were scanned sequentially with 20 mCi of each tracer using the CERASPECT system within 1 mo. Scanning began on average 11.5 +/- 2.8 min after 99mTc-HMPAO injection and 41.8 +/- 10.1 min after 99mTc-ECD. A ratio, R, was derived of count densities in "typically affected" brain structures (parietal and temporal association cortices) to "unaffected" structures (cerebellum, basal ganglia, thalamus, occipital cortex, and sensorimotor cortex).. Analysis of variance revealed significant interaction between diagnostic group and radiopharmaceutical (F = 4.71; df = 1.35; p = 0.04), with 99mTc-ECD demonstrating better separation of R values between AD patients and control subjects than 99mTc-HMPAO. Receiver operating characteristic (ROC) analysis, revealed no significant difference in the ability of the two tracers to correctly classify AD patients and control subjects. Both tracers showed high diagnostic accuracy (99mTc-ECD: sensitivity = 100%, specificity = 92%; 99mTc-HMPAO: sensitivity = 100%, specificity = 85%).. Technetium-99m-ECD shows greater contrast than 99mTc-HMPAO between affected and unaffected brain structures in AD when patients are compared to age-matched control subjects. Both tracers perform equally well in correctly classifying patients and control subjects.

Topics: Aged; Alzheimer Disease; Analysis of Variance; Brain; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; ROC Curve; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The aim of the study was to clarify, whether the selection of the reference-region and/or the reconstruction-filter influences the result of the semiquantitative analysis of a 99mTc-HMPAO-SPECT that was conducted to diagnose the dementia of the Alzheimer type (DAT).. A group of 19 DAT-patients according to the criteria of NINCDS-ADRDA and DSM-III-R was examined together with a comparison group (n = 14) with normal cerebral perfusion. Three reference-regions (cerebellum, whole slice, occipital cortex) and four reconstruction-filters (Hanning fc = 0.7 and 1.0 Nyquist; Butterworth (n = 8); fc = 0.5 and 0.9 Nyquist) were applied to twelve standardized regions of interest (per patient) respectively. The data was evaluated through a ROC-analysis.. It has been showed, that the bilateral parieto-temporal perfusion reduction as a characteristic of DAT depends on the filters and reference-regions used. The most secure separation of both groups of patients was obtained through a Butterworth-filter (n = 8; fc = 0.5) in combination with the cerebellum as reference-region.. The selection of the reference-region and the reconstruction-filter has an important influence on the results of a semiquantitative analysis. Therefore standardisation in dependency on the actual questioning is necessary.

Topics: Aged; Alzheimer Disease; Brain; Cerebellum; Equipment Design; Female; Humans; Male; Occipital Lobe; Organ Specificity; Organotechnetium Compounds; Oximes; Reference Standards; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

Twenty-three patients with Alzheimer's dementia (AD) in relatively early stages and 40 patients with other cognitive disorders of vascular or degenerative aetiology underwent neuropsychological examination and [99mTc]-HM PAO single photon emission computed tomography (SPECT). In contrast to the commonly accepted notion of a posterior temporoparietal reduction of tracer uptake as the typical SPECT pattern of AD, the most consistent feature found in the SPECT images of our AD patients was a hippocampal uptake deficit, associated with a variable degree of temporal, parietal and frontal deficit (extending from the posterior to the anterior regions), according to the severity of the disease. These results support the theory of AD as a "hippocampal dementia", at least in the early stages. Neuropsychological tests were found to be somewhat more specific and more accurate than SPECT in distinguishing AD from non-AD cases.

Topics: Aged; Alzheimer Disease; Humans; Neuropsychological Tests; Organotechnetium Compounds; Oximes; Retrospective Studies; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

This study examined whether psychosis in Alzheimer's disease is associated with cerebral perfusion patterns appreciable by single photon emission computed tomography (SPECT) scans.. All cooperative outpatients enrolled in an Alzheimer's disease research center with the diagnosis of probable Alzheimer's disease and a Clinical Dementia Rating of mild or moderate were interviewed with their primary caregivers. Current and past psychiatric functioning was assessed by using the Hamilton Depression Rating Scale, the Structured Clinical Interview for DSM-III-R, and the Behavioral Pathology in Alzheimer's Disease Rating Scale. Patients without premorbid psychosis received SPECT scans, and the scans of the patients with delusions or hallucinations (N = 30) were compared to the scans of patients without these symptoms (N = 16).. The patients with delusions (N = 29) had hypoperfusion of the left frontal lobe in relation to the right frontal lobe. The patients with hallucinations (N = 10) had hypoperfusion in the parietal lobe.. Psychotic patients with Alzheimer's disease had a pattern of cerebral blood flow deficits significantly different from that of nonpsychotic patients. This suggests that patterns of cerebral dysfunction may be expressed symptomatically as psychosis.

Topics: Alzheimer Disease; Ambulatory Care; Brain; Cerebrovascular Circulation; Comorbidity; Delusions; Frontal Lobe; Hallucinations; Humans; Organotechnetium Compounds; Oximes; Parietal Lobe; Psychiatric Status Rating Scales; Psychotic Disorders; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

It is quite difficult to confirm the diagnosis of demential disorders, including senile dementia of the Alzheimer type (SDAT) by clinical means only. Through the combination of 99mTc-HMPAO brain SPECT and serum vitamin B12 determination it was hoped to speed up and improve the diagnosis of SDAT. 116 patients who had been divided into four groups according to their defect pattern in the 99mTc-HMPAO brain SPECT 17 very probably had SDAT; of these 15 showed a defect-pattern with brain SPECT which could be associated to SDAT. The majority of SDAT patients had serum vitamin B12 levels in the lower normal range or pathologically below that range. Both investigations contributed to establishing the SDAT diagnosis without replacing other investigations. The determination of serum vitamin B12 does not require any major additional effort.

Topics: Aged; Alzheimer Disease; Brain; Cerebral Infarction; Dementia; Diagnosis, Differential; Humans; Organotechnetium Compounds; Oximes; Reference Values; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Vitamin B 12

To better understand cortical perfusion, we developed a method for a three-dimensional display technique with 99mTc-hexamethylpropyleneamine oxime (HMPAO) SPECT.. Twelve patients with higher cortical dysfunction due to Alzheimer's disease and 18 age-matched controls were examined. Data acquisition was performed after intravenous injection of 740 MBq of 99mTc-HMPAO. After reconstructing the transaxial images, the three-dimensional images were obtained by modified volume rendering, where the surfaces were displayed in the corresponding colors as the maximum cortical value within a depth of 2 cm.. In the control studies, almost all surface cortices were over 60% of the maximum cerebellar value. In Alzheimer's disease patients, areas of perfusion below 60% were detected in the temporo-parietal lesions and frontal lobe lesions in 6 of 12. These findings correlated with the neurological dysfunction.. This method provides realistic three-dimensional information about surface cortical perfusion, which was found to be useful in clinical investigations of higher cortical dysfunction due to degenerative or cerebrovascular diseases.

Topics: Alzheimer Disease; Brain; Cerebral Cortex; Cerebrovascular Circulation; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Single photon emission with computed tomography (SPECT) hexamethylphenylethyleneamineoxime technetium-99 images were analyzed by an optimal interpolative neural network (OINN) algorithm to determine whether the network could discriminate among clinically diagnosed groups of elderly normal, Alzheimer disease (AD), and vascular dementia (VD) subjects. After initial image preprocessing and registration, image features were obtained that were representative of the mean regional tissue uptake. These features were extracted from a given image by averaging the intensities over various regions defined by suitable masks. After training, the network classified independent trials of patients whose clinical diagnoses conformed to published criteria for probable AD or probable/possible VD. For the SPECT data used in the current tests, the OINN agreement was 80 and 86% for probable AD and probable/possible VD, respectively. These results suggest that artificial neural network methods offer potential in diagnoses from brain images and possibly in other areas of scientific research where complex patterns of data may have scientifically meaningful groupings that are not easily identifiable by the researcher.

Topics: Aged; Aged, 80 and over; Algorithms; Alzheimer Disease; Brain; Dementia, Vascular; Female; Humans; Male; Middle Aged; Neural Networks, Computer; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Topics: Alzheimer Disease; Brain; Cerebrovascular Circulation; Deoxyglucose; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Humans; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

A 52-year-old patient with mosaic Down's syndrome exhibiting clinical features of early dementia who underwent high resolution SPECT neuroimaging is reported. While a CT scan of the brain showed no abnormality, cranial SPECT confirmed the presence of marked cortical blood flow deficits.

Topics: Alzheimer Disease; Brain; Down Syndrome; Humans; Male; Middle Aged; Mosaicism; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Single-photon emission tomographic (SPET) images using technetium-99m labelled hexamethyl-propylene amine oxime were obtained from 97 patients diagnosed as having Alzheimer's disease, as well as from a comparison group of 64 normal subjects. Multiple linear regression was used to predict subject type (Alzheimer's vs comparison) using scintillation counts from 14 different brain regions as predictors. These results were disappointing: the regression equation accounted for only 33.5% of the variance between subjects. However, the same data were also used to train parallel distributed processing (PDP) networks of different sizes to classify subjects. In general, the PDP networks accounted for substantially more (up to 95%) of the variance in the data, and in many instances were able to distinguish perfectly between the two subjects. These results suggest two conclusions. First, SPET images do provide sufficient information to distinguish patients with Alzheimer's disease from a normal comparison group. Second, to access this diagnostic information, it appears that one must take advantage of the ability of PDP networks to detect higher-order nonlinear relationships among the predictor variables.

Topics: Aged; Alzheimer Disease; Brain; Female; Humans; Linear Models; Male; Middle Aged; Neural Networks, Computer; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Although specific patterns of technetium-99m exametazime [99mTc-hexamethylpropylene amine oxime (HMPAO)] brain single-photon emission tomography (SPET) uptake have been described for patients with dementia, no multi-institutional study has evaluated interobserver agreement. Interobserver agreement for 99mTc-HMPAO brain SPET uptake patterns in 50 clinically diagnosed demented subjects from four institutions were studied. Neurologists classified these subjects as presumed Alzheimer's disease (n = 21), confirmed Alzheimer's disease (n = 10), multi-infarct dementia (n = 9), HIV-related dementia (n = 7), or "mixed" (n = 3). In addition 20 normal (five per institution) 99mTc-HMPAO studies were included in a randomized blinded evaluation by three readers each from a different institution. Readers classified the general appearance of the images in one of four categories: normal, globally decreased uptake, focal areas of decreased uptake, and patchy changes in uptake. Consensus results show a sensitivity of 72% and specificity of 79% for identifying abnormalities in scans of demented subjects. Readers also rated 99mTc-HMPAO uptake in eight designated regions in each hemisphere. Significant reader agreement (P < 0.01) for the classification by general appearance and the ratings of regional uptake was obtained. This study demonstrates that interpretation of regional cerebral blood flow/SPET images is concordant across multiple institutions and readers.

Topics: AIDS Dementia Complex; Alzheimer Disease; Brain; Dementia, Multi-Infarct; Humans; Observer Variation; Organotechnetium Compounds; Oximes; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The value of hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) as a diagnostic test for Alzheimer's disease (AD) was assessed in 44 patients attending a Memory Clinic. A comprehensive physical and psychiatric examination and detailed neuropsychological tests were used to arrive at a clinical diagnosis, in accordance with NINCDS-ADRDA criteria. The mean patient age was 69 (range 59-84) years, and the mean score on the Mini-Mental State Examination (MMSE) was 24 (range 7-30). Of 26 patients with a clinical diagnosis of AD, only 15 demonstrated a scan pattern strongly suggestive of AD. Four scans were normal, four showed evidence of ischaemic change and three were in the category 'other', one of which showed bilateral frontal hypoperfusion, but normal temporoparietal flow. Of the eight patients considered by clinical criteria to be non-demented, no scan showed an AD pattern, but three showed an ischaemic pattern. Both of the patients diagnosed clinically as suffering from multi-infarct dementia showed SPECT scan evidence of ischaemic change. Of the remaining eight patients with other clinical diagnoses only one scan suggested AD. We conclude that the HMPAO SPECT scan appearances which arise from AD in the early stages of the disease do not on their own allow the disease to be accurately diagnosed, but they may be useful if interpreted in conjunction with other imaging techniques.

Topics: Aged; Alzheimer Disease; Brain; Female; Geriatric Assessment; Humans; Male; Memory Disorders; Organotechnetium Compounds; Outpatient Clinics, Hospital; Oximes; Referral and Consultation; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

This study evaluated the effect of using two different reference regions in the quantification of single-photon emission tomography (SPET). SPET scans of 30 patients with Alzheimer's disease (AD) and 30 patients with frontotemporal dementia were compared with the scans of ten age-matched controls. Regions of interest (ROIs) were defined on transaxial slices by a semi-automatic method. Regional cerebral blood flow indices (rCBFi) in each ROI were determined by normalizing the count densities to both cerebellar and occipital cortex reference regions. Mean rCBFi for each ROI were calculated for the patient and control groups and significant group differences determined. The number and topographical distribution of ROIs with significant group differences varied depending upon the choice of reference region. The magnitude of these differences was greatest when the cerebellum was used as the reference region. The disparity between results obtained with the two reference regions was most apparent in the AD group. The reasons for these differences are discussed and we conclude that the cerebellum is the more appropriate choice of reference region in the quantification of SPET in primary degenerative dementia.

Topics: Alzheimer Disease; Brain; Cerebellum; Cerebrovascular Circulation; Dementia; Female; Frontal Lobe; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

99mTc-HM-PAO single photon emission computed tomography (SPECT) was used to image 30 patients referred for the assessment of dementia. SPECT images revealed various patterns of regional cerebral perfusion (rCBF) in the subgroups of patients with the clinical diagnoses of Alzheimer's disease (AD, n = 14), Pick's disease (n = 1), and multi-infarct dementia (n = 7). In three patients, SPECT clarified the clinical differential diagnostic possibilities. Using a relative rCBF quantification technique, the relationship between specific cognitive impairments and rCBF in the AD patients was determined. There was a significant correlation between language impairment and left hemisphere hypoperfusion, whereas, apraxia correlated with hypoperfusion in the left parietal region. Thus, HM-PAO SPECT is useful as an aid in the differential diagnosis of dementia and the technique of relative rCBF quantification with SPECT may contribute to the understanding of the clinico-anatomical relations of cognitive deficits in dementia.

Topics: Aged; Alzheimer Disease; Brain; Cerebrovascular Circulation; Cognition Disorders; Dementia; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

A computer-assisted mapping program was developed to determine changes of cerebral perfusion in normal and pathological aging using single photon emission computer tomography (SPECT) and 99mTc-hexamethylpropyleneamine oxime (HMPAO). The software program outlined the cortex on 14 adjacent brain slices, and superimposed a ring of 12 regions of interest on each slice. Regional/global and regional/cerebellar relative flow values were calculated in 27 patients with clinically diagnosed Alzheimer's disease (AD) (mean age 71 years, SD 7.6) and in 10 normal controls (mean age 73.7 years, SD 7.3). The Dementia Rating Scale (DRS) was used to assess mental status in all subjects. Multiple regression analysis demonstrated a significant correlation between relative flow values and the DRS score. Regional/cerebellar (R = 0.88, p < 0.0001) relative flow values were a better indicator of cortical impairment than regional/global relative flow values (R = 0.68, p = 0.003). Of the brain regions of interest, the left parietal flow values correlated best with the DRS score (r = 0.83, p < 0.0001), a cutoff value of 77 accurately classifying 80% of the normals and 100% of the patients diagnosed as having Alzheimer's disease. The data show that computer-assisted mapping of SPECT can provide semiquantitative flow values with high diagnostic accuracy.

Topics: Aged; Alzheimer Disease; Brain; Cerebrovascular Circulation; Female; Humans; Image Interpretation, Computer-Assisted; Male; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

We studied the diagnostic accuracy of single-photon emission computed tomography (SPECT) with technetium 99m-labeled hexamethylpropylene amine oxime (Tc 99m HMPAO) in 48 patients with probable Alzheimer's disease (AD) according to NINCDS-ADRDA criteria and in 60 controls recruited from a population-based study. With logistic regression, we identified decreased temporal regional cerebral blood flow as the best discriminating variable between patients and controls. Receiver-operator characteristic curves showed that the discriminative ability of SPECT improved with increasing dementia severity. With specificity set at 90%, sensitivity figures were 42% in mild, 56% in moderate, and 79% in severe AD. The diagnostic gain as a function of the prior probability of the disease being present was computed for those with mild AD. When the prior probability varied at around 50%, the diagnostic gain for mild AD patients was substantial (a maximum of 34%) for a positive test result but poor for a negative test result. The results suggest that the practical usefulness of SPECT as a diagnostic adjunct in patients suspected of having mild AD is confined to situations in which, on clinical grounds, there is considerable diagnostic doubt.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Cerebrovascular Circulation; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; ROC Curve; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Regional cerebral blood flow (rCBF) was measured with high resolution brain dedicated single photon emission computer tomography (SPECT) and [99mTc]-d,l-hexamethyl-propylene-amine-oxime (HMPAO) in 25 patients with probable Alzheimer's disease and in 25 control subjects, selected according to rigorous inclusion and exclusion criteria. The aim was to analyse the topography of rCBF deficits in individual patients. In the group of patients with Alzheimer's disease as a whole, global CBF was reduced, but a factorial analysis of variance did not show disproportionate reduction of rCBF in any brain region. A parametric analysis of the rCBF data in individual patients was carried out with reference to normal values for internal rCBF ratios and to 13 different abnormal rCBF patterns. These theoretical patterns were predefined by showing significant hypoperfusion in at least one, or in any relevant combination of two, three, or four, of four major brain regions (a left and right frontal and a left and right posterior region). All patients with Alzheimer's disease and none of the control subjects had an abnormal rCBF pattern. Eleven of the 13 different patterns were seen in the patients. Frontal changes were seen in 19 (76%) of the patients, more often than previously reported. No single Alzheimer's disease pattern could be derived from our data. The number of regions with hypoperfusion, but not the presence of frontal changes, correlated significantly with the duration of disease. It is concluded that a clinical diagnosis of probable Alzheimer's disease is associated with heterogeneous patterns of rCBF deficits as measured with SPECT and [99mTc]-d,l-HMPAO. This heterogeneity may reflect different stages of the disease or cognitive subtypes and help explain published discrepancies concerning the topography of hypoperfusion in Alzheimer's disease. An analysis of individual rCBF data may add important information in the investigation of diseases with heterogeneous effects on the brain.

Topics: Adult; Aged; Alzheimer Disease; Cerebral Cortex; Cerebrovascular Circulation; Female; Frontal Lobe; Humans; Male; Middle Aged; Occipital Lobe; Organotechnetium Compounds; Oximes; Prospective Studies; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Xenon Radioisotopes

This report describes a comparative study between technetium-99m ethyl cysteinate dimer (ECD) and 99mTc-hexamethylpropylene amine oxime (HMPAO) in five neurological patients. The conversion kinetics of the tracers in the blood from forms capable of diffusion across the blood-brain barrier to non-diffusible forms were studied by arterial sampling and rapid octanol extraction. We observed that HMPAO has a faster conversion rate in the blood but that the fraction of the injected dose available for brain extraction is higher than in the case of ECD. Regional brain concentrations of the tracers were measured with single-photon emission tomography (SPET) 35 min and 60 min after the injection and remained stable within this interval. On the basis of the measurements of the arterial input and of SPET brain concentrations of the tracers, the regional steady-state influx constants (Ki in ml/min/g) were determined for several brain regions. In the grey matter the Ki values were (mean +/- SD) 0.32 +/- 0.03 and 0.35 +/- 0.04 for HMPAO and ECD, respectively; in the white matter the values were 0.23 +/- 0.01 and 0.23 +/- 0.02, respectively. The Ki values of the two tracers in corresponding regions were closely correlated (P < 0.001). The correspondence of the Ki values of ECD and HMPAO demonstrates that ECD can also be considered a tracer that may be used for quantitative measurements of brain perfusion.

Topics: Aged; Alzheimer Disease; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Artificial neural networks have been applied to a variety of pattern recognition tasks in medical imaging and have been shown to be a powerful classification tool. The potential usefulness to discriminate normal from abnormal cerebral perfusion patterns was investigated.. Cerebral perfusion imaging with 99mTc-labeled hexamethylpropyleneimine oxime was performed on 52 normal control subjects, 29 patients with clinically diagnosed Alzheimer's disease (AD) and 25 patients with chronic cocaine polydrug abuse. Each study was registered and scaled to a common anatomic coordinate system, yielding 120 standardized cortical regions. A back-propagation neural network classifier based on regional perfusion was used to classify normal and abnormal perfusion patterns. The neural network was trained to discriminate patients with AD from age-matched normal controls and cocaine polydrug abuse patients from normal controls. The performance of the neural network in these two tasks was evaluated quantitatively by receiver operating characteristic (ROC) analysis using cross-validation.. For patients with AD, the area under the ROC curve was 0.93 +/- 0.04. When testing with the cocaine polydrug abuser data, the area under the ROC curve was 0.89 +/- 0.04.. Neural networks provide a potentially useful tool in the decision-making task to discriminate patients with AD and cocaine abuse from normal controls.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Brain; Cocaine; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Neural Networks, Computer; Organotechnetium Compounds; Oximes; Radionuclide Imaging; ROC Curve; Substance-Related Disorders; Technetium Tc 99m Exametazime

SPECT studies of regional cerebral perfusion with a high-resolution system were compared to PET studies of regional cerebral glucose utilization (rCMRglc) in 21 patients with probable Alzheimer's disease (AD). Ten normal subjects were also evaluated with SPECT and 10 with PET.. rCMRglc (for PET) and counts (for SPECT) in the associative cortices were normalized to the average rCMRglc, and counts in the calcarine cortex and basal ganglia were considered as a "reference area" to obtain a ratio. The ratio differences between patients and controls were tested with ANOVA performed separately for PET and SPECT.. The difference between probable AD patients and controls was significant for both PET (p < 0.00001) and SPECT (p < 0.005); this difference was significant for the frontal, temporal and parietal cortices (p < 0.0001) for PET, and for the temporal (p < 0.005) and parietal (p < 0.001) cortices for SPECT. Temporo-parietal defects were detected in all subjects with PET and in 90% with SPECT.. PET and SPECT are able to detect characteristic temporo-parietal abnormalities in probable AD. However, the presence of abnormalities in other associative areas is better evaluated with PET.

Topics: Adult; Aged; Alzheimer Disease; Deoxyglucose; Female; Fluorodeoxyglucose F18; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

A normal atlas for HMPAO rCBF SPECT images was obtained from images of 53 normal controls. Following image registration and normalization, a mean image was extracted, while images representing correlated normal deviants were identified using principal component analysis. These images formed the "building blocks" of the atlas. For subsequent images, the atlas was used to create a "nearest normal equivalent" image, which was compared to a residual standard deviation image to determine the significance of deviations in the new image.. Images from 30 patients (10 with Alzheimer's disease; 12 with single or multiple infarcts; and 8 normals) were analyzed.. Using an optimal decision level, 10/10 patients with Alzheimer's disease and 11/12 patients with infarcts were correctly identified, with only one false-positive resulting. We utilized a database of images obtained from normal controls to create a normal atlas.

Topics: Alzheimer Disease; Brain; Cerebral Infarction; Cerebrovascular Disorders; Humans; Methods; Organotechnetium Compounds; Oximes; Reference Values; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The uptake, at rest, of 99mTc-exametazime into different brain regions was compared using SPECT for 20 elderly subjects with major depressive disorder, 20 with Alzheimer-type dementia, and 30 age-matched normal volunteers. Uptake was referred to calcarine-occipital cortex as a reference sensory area. Cross-sectional differences between the three groups were highly statistically significant, but reflected primarily the reductions in cortical uptake in the Alzheimer group. A detailed comparison of depressed patients and controls identified decrements in anterior cingulate, temporal and frontal cortex and in caudate and thalamus in men only. These decrements were correlated with impairment of performance on a trail-making task, but were also associated with continuing treatment with antidepressants or benzodiazepines. However, most depressed patients had quantitatively normal scans for posterior parietal association cortex, and this suggests that SPECT may find a limited role in the differential diagnosis of depression and dementia. The reduced brain function in some depressed patients may parallel the findings from studies of brain structure in elderly depressives; there was between good outcome at 6-18 months and increased tracer uptake in subcortical areas.

Topics: Age of Onset; Aged; Aged, 80 and over; Alzheimer Disease; Analysis of Variance; Brain; Cognition Disorders; Dementia; Depressive Disorder; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Sex Factors; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To improve the diagnostic utility of brain single-photon emission computed tomography (SPECT) in Alzheimer's disease (AD), we have developed and evaluated an objective method of differentiating patients and healthy elderly controls using a quantitative image analysis protocol. HMPAO-SPECT image datasets from 29 patients with probable AD and 78 age-matched controls were registered to a common anatomic frame of reference. Activity levels within 120 standardized cortical volumes were determined by an automated procedure. Subjects were classified into normal and AD groups by quadratic discriminant analysis using two features: global average activity level and average normalized activity levels within the two clusters of standardized volumes identified as most significantly different in AD by analysis of covariance. The classification used split-half replication to ensure valid results. Classification performance quantified by the area under a binormal ROC curve fitted to the data was 0.923 +/- 0.036; at a threshold likelihood ratio of 1, the sample sensitivity was 91% and specificity was 86%. We conclude that quantitative SPECT accurately distinguishes AD patients from elderly controls.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Brain; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The aim of the present study was to see whether HMPAO-SPECT may contribute to the differentiation between dementia of the Alzheimer type (DAT) and major depression (MD). The results in 77 patients with memory impairment were evaluated. 48 patients suffered from DAT and 29 from MD. Initially, the defects in SPECT imaging were attributed to a cerebral region and the degree of decrease was evaluated (-1/-2/-3). Thereafter, the results were classified by 7 categories. In some of these categories an accumulation of cases of either DAT or MD was found. 35% of the patients suffering from DAT had bilateral defects with distinct (> -1) parietal/parietotemporal hypoperfusions, but no patient with MD showed this perfusion pattern. 62% of the patients with MD had unilateral defects but only 31% of the patients with DAT. The present study demonstrates that only 35% of all patients suffering from DAT show a perfusion pattern, thought earlier as "pathognomonic" for this disease. This perfusion pattern--if it exists--may be used as a safe criterion to exclude MD. Beyond that no clearcut ("specific") perfusion pattern may be recognized but unilateral defects point to MD.

Topics: Aged; Alzheimer Disease; Depressive Disorder; Female; Humans; Male; Memory Disorders; Organotechnetium Compounds; Oximes; Retrospective Studies; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Fourteen young patients with Down's syndrome (nine males, five females, age range 8-30 years) were studied. 99Tcm-hexamethylpropylene amine oxime (HMPAO) brain single photon emission computed tomography (SPECT) was performed to evaluate regional cerebral blood flow (rCBF). Two experienced nuclear medicine physicians analysed the results of the SPECT by visual interpretation. The SPECT in all 14 patients with Down's syndrome invariably showed significantly unilateral perfusion defects in the temporal-parietal-occipital region, occasionally combined with small perfusion defects over other discrete cerebral areas. In this preliminary study, 99Tcm-HMPAO brain SPECT in the patients with Down's syndrome were abnormal. Patterns of rCBF in Down's syndrome were similar to the usual images of rCBF in Alzheimer's disease reported in the literature. Our findings provide new evidence of the similarities between Down's syndrome and Alzheimer's disease.

Topics: Adolescent; Adult; Alzheimer Disease; Cerebrovascular Circulation; Child; Down Syndrome; Female; Humans; Male; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The pattern of abnormal distribution of the single photon emission computed tomography (SPECT) cerebral blood flow tracer 99m-technetium-hexamethylpropyleneamine oxime (99Tcm-HMPAO) was investigated in 14 patients with clinically diagnosed Alzheimer's disease (AD) who subsequently had post-mortem confirmation of the disease and also in 14 elderly control subjects. These abnormalities were compared with computed tomography (CT) scans to investigate the degree to which the focal SPECT deficits were due to atrophy. The results show that SPECT imaging with 99Tcm-HMPAO and CT scanning both have a higher incidence of abnormality in AD patients than in controls and that the difference between patients and controls is greater with SPECT than with CT. Frontal SPECT and CT abnormalities in moderate/severe Alzheimer's disease occur as frequently as temporal/occipital abnormalities but the latter are rare in control subjects. Around 50% of the SPECT deficits occur in CT normal brain regions, showing that atrophy is not the sole cause of SPECT deficits.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Cerebrovascular Circulation; Humans; Longitudinal Studies; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

99m-technetium-hexamethylpropylene-amineoxine (99m-Tc-HMPAO) single-photon-emission-computer-tomography (SPECT)-scans and spectral analyzed electroencephalogram (EEGs) of 20 patients with Alzheimer's disease (AD) were studied. A significant correlation was found between the temporoparietal-cerebellar-ratio (TP/C-ratio) of the SPECT-scan and the peak frequencies of leads T3-T5, C3-P3, and C4-P4 of the EEG. In addition a significant negative correlation between the TP/C-ratio and the theta/alpha-ratio (t/a-ratio) of leads T3-T5, T4-T6, C3-P3, and C4-P4 was demonstrated. Our study demonstrates that slowing of the EEG parallels a decrease in blood flow in the temporoparietal regions in AD-patients. Both findings could be parallel phenomena of regional hypometabolism.

Topics: Adult; Aged; Alzheimer Disease; Electroencephalography; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Occipital Lobe; Organotechnetium Compounds; Oximes; Parietal Lobe; Signal Processing, Computer-Assisted; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

Topics: Alzheimer Disease; Brain; Cerebral Aqueduct; Dementia; Diagnosis, Differential; Female; Humans; Hydrocephalus; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

A loss of acetylcholine is one of the most consistent neurochemical findings in Alzheimer's disease (AD) post-mortem, but the debate concerning receptor abnormalities is unresolved. The aim of this investigation was to measure the density of acetylcholine muscarinic receptors in AD patients at various stages in the disease (N = 8) by synthesising a radio-iodinated version of quinuclidinyl benzilate QNB, a potent muscarinic antagonist. Deficits were identified by comparison with a control data set obtained from four elderly volunteers and then compared to the deficit in total functional activity in the same brain regions measured using the cerebral perfusion tracer technetium-99m hexamethylpropylene amine oxime. Iodine-123 (R,R)quinuclidinyl benzilate (QNB) was synthesised using a CuI assisted nucleophilic aromatic exchange reaction. 160 MBq of the radioligand (specific activity 400 Ci/mmol: dose 90 ng/kg) was administered to each subject. Diagnosis of AD was made using the CAMDEX and DSMIIIR criteria with a physical examination, full blood screen, CT and chest X-ray. All subjects were scanned at 21 h post injection on an SME810 emission tomograph. 123I(R,R)QNB activity in the controls was found to be consistent with the known distribution of muscarinic receptors with no activity in the cerebellum and low activity in the thalamus. In the AD patients deficits in 123I-QNB binding which exceeded the corresponding total functional regional perfusion deficit were not found in six of the patients and were observed only in the two most severely affected patients, both of whom were untestable on the cognitive battery.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Brain Chemistry; Cerebrovascular Circulation; Female; Humans; Iodine Radioisotopes; Middle Aged; Organotechnetium Compounds; Oximes; Quinuclidinyl Benzilate; Radionuclide Imaging; Receptors, Muscarinic; Technetium Tc 99m Exametazime

Thirty-five patients with a clinical diagnosis of probable Alzheimer's disease underwent computed tomography (CT) and regional cerebral blood flow (rCBF) studies using single photon emission computed tomography (SPECT). Two sets of images in each subject were scored for the extent of structure and function changes. Thirty-four of 35 patients had various degrees of atrophy on CT, 33 of whom also had perfusion deficits of varying severity. One patient with normal CT had perfusion deficits, and another patient with a normal perfusion pattern had changes on CT. Regional perfusion deficits on SPECT were seen with and without associated changes on CT. Correlations were studied between CT and SPECT scores using Spearman's rank correlation coefficients. While regional scores on CT and SPECT did not significantly correlate, the total and left hemisphere scores on two sets of images showed fair correlations (r = 0.425 and r = 0.535, respectively, P less than 0.01). The correlations between cognitive performance in patients as assessed on Mini-Mental State Examination (MMSE) and CAM-COG and perfusion scores were highly significant while CT scores showed lower correlations. These findings suggest that the relationship between structural and functional changes in Alzheimer's disease is not straightforward and that the extent of changes in function as assessed by regional cerebral blood flow studies is a reliable measure of deficits in cognitive function.

Topics: Aged; Alzheimer Disease; Cerebrovascular Circulation; Cognition Disorders; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Regional cerebral blood flow was assessed in 35 patients with Alzheimer's disease and the same number of matched normal volunteers. Images were scored for regional perfusion deficits. Mildly demented patients had parietal and temporal perfusion deficits, often unilateral. Moderate to severely demented patients had bilateral temporal and parietal perfusion deficits. All severely demented patients also had involvement of both occipital regions. Frontal lobe deficits were seen in 14 patients. Left cortical perfusion deficits were more severe than the right cortical perfusion deficits in general. Patients with early onset of the disease showed left frontal deficits, more often, however, the total perfusion deficit scores in early and late onset groups were not statistically significant. Also, the cognitive performance scores were not statistically significant in these two groups. These results suggest a stage-dependent reduction in regional cerebral blood flow in patients with Alzheimer's disease.

Topics: Aged; Alzheimer Disease; Cerebrovascular Circulation; Cognition Disorders; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime

For the purpose of facilitating anatomical localization in interpretation of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) brain single photon emission tomographic (SPECT) scans, a stereotaxic proportional grid system was applied in the form of an interactive computer program. This method takes advantage of a rotating gamma camera system which permits planar scout imaging for the determination of anatomical reference lines, and standardization of tomographic slices for brain size. Using measurements made on a lateral planar HMPAO image, proportional grids were constructed onto standardized transaxial images. This method was implemented for 33 clinical HMPAO SPECT studies. It required less than 15 min of an operator's time. This simple and practical neuroanatomical localization technique can be instrumental as an aid to the interpretation of routine clinical HMPAO SPECT images.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Brain; Brain Diseases; Brain Injuries; Dementia; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Software; Stereotaxic Techniques; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The effects of the choice of the reference region in determining the relative regional cerebral blood flow (rCBF) using 99Tcm-hexamethylpropylene amine oxime (HMPAO) single photon emission tomography (SPECT) have been studied in order to establish or exclude it as a cause of inconsistencies in these studies. Relative rCBF was estimated by normalizing the regional count densities to two reference regions, the cerebellum and the whole slice, in 35 patients with Alzheimer's disease (AD), 25 patients with chronic schizophrenia (SCH) and the same number of matched normal volunteers. The statistical significance of the differences in rCBF between patients and their matched normals varied in the two sets of rCBF data. Smaller differences were highly significant while some larger differences were of less significance with whole slice normalization. The results suggest that the choice of reference region is one of the causes resulting in discrepancies in the results from various centres. The need to use a standard reference region is indicated.

Topics: Alzheimer Disease; Cerebrovascular Circulation; Chronic Disease; Female; Humans; Male; Organotechnetium Compounds; Oximes; Reference Values; Schizophrenia; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Thirty five patients with dementia of the Alzheimer type (DAT) and 35 controls matched for age, sex and handedness were investigated using single photon emission computer tomography (SPECT) with 99m technetium HMPAO. Regional cerebral blood flow (rCBF) was assessed semi-quantitatively in 18 cortical and 4 subcortical areas by normalising mean information density in each region to cerebellar mean information density. Analysis revealed significantly reduced rCBF to temporal, parietal, frontal and left occipital cortex in the patients whilst blood flow to subcortical areas showed no differences between the 2 groups. In addition, significant left-sided cortical hypoperfusion was seen in the DAT group but not in controls. When patients were sub-divided on the basis of disease severity, those with mild disease showed temporal, parietal and left frontal changes with more severely affected patients also showing right frontal and left occipital involvement. rCBF patterns did not distinguish between presenile and senile onset cases once duration and severity of illness were controlled. Eight cortical areas were also rated visually for perfusion deficits on a simple 4 point scale. Perfusion deficits were detected in 34 of 35 patients but in only 4 of 35 controls. In the DAT group significant correlations were found between many of the neuropsychological tests used and rCBF. Memory correlated with left temporal activity, praxis, perception, object assembly and block design with right parietal activity and language with activity throughout the left hemisphere. Significant correlations were also seen between subcortical and cortical blood flow, possibly explaining the correlations observed between many of the neuropsychological tests and thalamic blood flow.

Topics: Aged; Alzheimer Disease; Brain; Brain Mapping; Cerebral Cortex; Cognition Disorders; Dominance, Cerebral; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Organotechnetium Compounds; Oximes; Regional Blood Flow; Technetium Tc 99m Exametazime; Thalamus; Tomography, Emission-Computed, Single-Photon

Brain single photon emission computed tomography (SPET) using 99mTcm-hexamethylpropyleneamine oxime (HMPAO) was performed in 37 patients satisfying the standard clinical criteria of Alzheimer's disease (AD), correlating results with patient's age of onset, duration of illness, severity of dementia, neuropsychological impairment, computed tomography (CT) and EEG findings. All patients had abnormal SPET: 23 were bilaterally symmetric, 10 were bilaterally asymmetric and four showed unilateral low regional cerebral perfusion. Low perfusion in bilateral parietal regions was the most consistent finding and was present alone or with other abnormal regions in 31 patients (84%). The only significant clinical correlation was found between asymmetric SPET changes and onset of disease before the age of 65 years. Fifty per cent of patients with presenile onset, but only 19% with senile onset had asymmetric low regional cerebral perfusion. Fifteen of the 36 patients had normal brain CT scans, and 9 of 31 patients receiving EEG examination had normal results. Although clinical evaluation is the most valuable diagnostic tool, brain SPET is a sensitive test for physiological investigation in AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Alzheimer's disease produces regional abnormalities in brain blood flow and metabolism that may result in recognizable scintigraphic patterns. We determined the predictive value of 99mTc-HMPAO SPECT for the presence of Alzheimer's disease based on a prospective study of 132 consecutive patients coming to our nuclear medicine clinical unit for evaluation of their memory loss or cognitive abnormalities. During clinical follow-up averaging 10.1 mo, a final diagnosis was established in 113 patients, 52 of which had Alzheimer's disease. The probability of Alzheimer's disease was determined for seven scintigraphic patterns. The probability was 19% that patients with memory loss and normal perfusion had Alzheimer's disease. For abnormal perfusion patterns, the probability of Alzheimer's disease was 82% with bilateral temporoparietal defects, 77% with bilateral temporoparietal defects with additional defects, 57% with unilateral temporoparietal defects, 43% with frontal defects only, 18% with other large defects and 0% with multiple small cortical defects. We conclude that for 99mTc-HMPAO SPECT the predictive value of bilateral temporoparietal defects for Alzheimer's disease is high, while the perfusion patterns of unilateral temporoparietal perfusion defects and frontal defects only, which occur in 20% of patients with Alzheimer's disease, are not predictive of that disease.

Topics: AIDS Dementia Complex; Alzheimer Disease; Cerebrovascular Circulation; Dementia, Vascular; Diagnosis, Differential; Humans; Organotechnetium Compounds; Oximes; Parkinson Disease; Predictive Value of Tests; Probability; Prospective Studies; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Topics: Alzheimer Disease; Humans; Organotechnetium Compounds; Oximes; Prospective Studies; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

SPECT with Tc-99m HM-PAO as a radiopharmaceutical was performed in 17 patients meeting research criteria for Alzheimer's disease (AD), in 10 patients with a clinical diagnosis of multi-infarct-dementia (MID) and in 12 healthy volunteers. Regional tracer uptake was measured in frontal, parietal, and temporoparietal regions. A statistically significant decrease of tracer uptake in the temporoparietal region was found in AD-patients compared with controls. AD-patients showed less activity in this region than MID-patients, but this difference did not reach statistical significance. In both AD- and MID-patients decrease of tracer uptake was not correlated with dementia severity. We conclude that SPECT brain imaging is not yet ready for routine use in the distinction between AD and MID.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Analysis of Variance; Brain; Dementia, Multi-Infarct; Female; Humans; Male; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Alzheimer's disease often occurs in patients with Down's syndrome. SPECT scanning with I-123 IMP and Tc-99m HMPAO identifies decreased cerebral perfusion and metabolism in these patients at lower cost. In this case, SPECT scanning revealed changes in Alzheimer's disease in a Down's syndrome patient.

Topics: Alzheimer Disease; Amphetamines; Brain; Down Syndrome; Humans; Iodine Radioisotopes; Iofetamine; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

A method for registering three-dimensional CT, MR, and PET data sets that require no special patient immobilization or other precise positioning measures was adapted to high-resolution SPECT and MRI and was applied in 14 subjects (five normal volunteers, four patients with dementia (Alzheimer's disease), two patients with recurrent glioblastoma, and three patients with focal lesions (stroke, arachnoid cyst and head trauma]. T2-weighted axial magnetic resonance images and transaxial 99mTc-HMPAO and 201Tl images acquired with an annular gamma camera were merged using an objective registration (translation, rotation and rescaling) program. In the normal subjects and patients with dementia and focal lesions, focal areas of high uptake corresponded to gray matter structures. Focal lesions observed on MRI corresponded to perfusion defects on SPECT. In the patients who had undergone surgical resection of glioblastoma followed by interstitial brachytherapy, increased 201Tl corresponding to recurrent tumor could be localized from the superimposed images. The method was evaluated by measuring the residuals in all subjects and translational errors due to superimposition of deep structures in the 12 subjects with normal thalamic anatomy and 99mTc-HMPAO uptake. This method for superimposing magnetic resonance and high-resolution SPECT images of the brain is a useful technique for correlating regional function with brain anatomy.

Topics: Alzheimer Disease; Arachnoid Cysts; Brain; Brain Injuries; Cerebrovascular Disorders; Glioma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon

To evaluate the usefulness of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) in suspected dementia we studied 160 consecutively imaged elderly patients from our hospital's memory disorder clinic. The diagnosis was based on clinical data, laboratory tests, neuropsychological examination, computed tomography (CT) and EEG. The patients were divided into six diagnostic categories: Alzheimer's disease (AD), multi-infarct dementia (MID), frontal lobe-type dementia (FTD), vascular encephalopathy not fulfilling the criteria of dementia, specific organic conditions, and psychiatric disorders. SPECT images were assessed without knowing the clinical diagnosis, and divided into AD pattern, FTD pattern, MID pattern, abnormal but unclassifiable, and normal. Twenty-three of 36 patients with clinical AD, 25/33 patients with clinical MID, and 2/5 patients with clinical TFD had compatible SPECT patterns. SPECT distinguished AD from MID in the majority (80%) of cases. In patients with depression or anxiety SPECT was abnormal in 16/21 cases, suggesting that SPECT may give early clues to the presence of an underlying organic disease in such elderly patients. Thus, SPECT with 99Tcm-HMPAO seems to be useful in the diagnosis of suspected dementia.

Topics: Aged; Alzheimer Disease; Cerebrovascular Circulation; Dementia; Dementia, Multi-Infarct; Diagnosis, Differential; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Regional cerebral perfusion was evaluated by single photon emission computed tomography (SPET) using technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO) as a tracer, in 13 control subjects and 44 age-matched patients suffering from dementia of the Alzheimer's type (DAT, n = 19), presumed Pick's disease (n = 5), idiopathic Parkinson's disease with dementia (DPD, n = 15) and progressive supranuclear palsy (PSP, n = 5). HMPAO uptake was measured in the superior frontal, inferior frontal, parietal, temporal and occipital cortices, and the perfusion values were expressed as cortical/cerebellar activity ratios. As compared with controls, tracer uptake ratios in the DAT group were significantly reduced over all cortical regions, with the largest defects in the parieto-temporal and superior frontal cortices. A marked hypoperfusion affecting the superior and inferior frontal cortices was found in Pick's disease, whereas a mild but significant hypoperfusion was observed only in the superior frontal cortex of patients with PSP. In the DPD group, HMPAO uptake was significantly reduced in the parietal, temporal and occipital cortices, but not in the frontal cortex. These results show that DAT and DPD share an opposite anteroposterior HMPAO uptake defect as compared with the Pick's and PSP groups.

Topics: Aged; Alzheimer Disease; Brain; Dementia; Female; Humans; Male; Organotechnetium Compounds; Oximes; Parkinson Disease; Supranuclear Palsy, Progressive; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Regional cerebral blood flow was studied in 7 patients with clinically suspected Alzheimer's disease and 10 normal controls by single photon computed emission tomography (SPECT) using HM-PAO. All patients with Alzheimer's disease and no controls had parietal lobe hypoperfusion which was usually bilateral. In patients with more severe dementia hypoperfusion extended into the frontal lobes. Parietal lobe hypoperfusion corresponds to parietal lobe degeneration which is the one of the first neocortical regions to show the typical degenerative changes of Alzheimer's disease. SPECT with HM-PAO is a non-invasive investigation available in most nuclear medicine departments and complements existing tests in the routine evaluation of patients presenting with dementia.

Topics: Aged; Alzheimer Disease; Cerebrovascular Circulation; Female; Functional Laterality; Humans; Male; Middle Aged; Neurologic Examination; Organotechnetium Compounds; Oximes; Parietal Lobe; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Patients with Alzheimer disease (AD) had reduced regional cerebral blood flow (rCBF) in the posterior parietotemporal region compared with controls, as determined with technetium-99m hexamethyl propyleneamine oxime and single photon emission tomography. Central cholinergic stimulation with physostigmine produced a focal increase in rCBF in the posterior parietotemporal region in the patients with AD but not in controls.

Topics: Aged; Alzheimer Disease; Cerebral Cortex; Dominance, Cerebral; Humans; Neuropsychological Tests; Organotechnetium Compounds; Oximes; Physostigmine; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Patients with Alzheimer disease (AD) had reduced regional cerebral blood flow (rCBF) in the posterior parietotemporal region compared with controls, as determined with technetium-99m hexamethyl propyleneamine oxime and single photon emission tomography. Central cholinergic stimulation with physostigmine produced a focal increase in rCBF in the posterior parietotemporal region in the patients with AD but not in controls.

Topics: Aged; Alzheimer Disease; Analysis of Variance; Cerebrovascular Circulation; Drug Evaluation; Female; Glycopyrrolate; Humans; Infusions, Intravenous; Male; Middle Aged; Organotechnetium Compounds; Oximes; Parasympathetic Nervous System; Parietal Lobe; Physostigmine; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

We compared I-123 IMP and 99m-Tc HMPAO SPECT studies with 0-15 H2O and F-18 FDG PET studies, and evaluated the clinical significance of SPECT studies in dementia. Seventeen patients including 9 patients with Alzheimer's disease, 3 patients with Pick's disease and 5 patients with multi-infarct dementia were studied. IMP and HMPAO SPECT studies could not detect mildly affected areas when compared with FDG PET. However, they revealed decreased perfusion in the bilateral parietal regions in Alzheimer's disease and in the bilateral frontal regions in Pick's disease, while MRI and/or CT showed mild to moderate cerebral atrophy. IMP and HMPAO SPECT studies can be easily performed in clinical practice, and these findings were useful in the differential diagnosis of dementia. Our preliminary results suggested that SPECT studies with I-123 IMP and Tc-99m HMPAO, despite their limitations, are useful in the differential diagnosis of dementia.

Topics: Aged; Alzheimer Disease; Amphetamines; Dementia; Dementia, Multi-Infarct; Female; Humans; Iodine Radioisotopes; Iofetamine; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

A new semi-automatic method for quantifying regional cerebral uptake of 99m technetium-hexamethylpropylene amine oxime (99mTc-HMPAO) was used to assess single photon emission tomograms from 5 normal subjects, 14 patients with Alzheimer's disease, 14 patients with dementia of frontal lobe type and 4 patients with dementia with motor neurone disease. Uptake in both posterior cortical regions, although not in other regions, was significantly lower (P less than 0.05) in Alzheimer's disease than in normal controls. Conversely in both dementia of frontal lobe type and dementia with motor neurone disease, uptake was significantly reduced (P less than 0.05) compared with controls in all anterior cortical regions but not in posterior regions. Numerical findings in each disease mirrored the pattern of reduced tracer uptake previously reported by visual assessment. Nine patients were re-examined after an interval of at least 1 year. Comparison of follow-up scans with original images showed significant decreases in mid-anterior, left anterior and left posterior cortical uptake (P less than 0.01) in patients with Alzheimer's disease and in left middle, left posterior and right posterior cortical uptake (P less than 0.01) in patients with dementia of frontal lobe type. The method of quantification may be a useful adjunct to the visual assessment of single photon emission tomograms.

Topics: Alzheimer Disease; Brain; Dementia; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The aim of this study was to compare technetium-99m-hexamethylpropyleneamineoxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) with regional cerebral blood flow (rCBF) imaging using positron emission tomography (PET). As investigation of dementia is likely to be one of the main uses of routine rCBF imaging, 18 demented patients were imaged with both techniques. The PET data were compared quantitatively with three versions of the SPECT data. These were, first, data normalized to the SPECT cerebellar uptake, second, data linearly corrected using the PET cerebellar value and, finally, data Lassen corrected for washout from the high flow areas. Both the linearly-corrected (r = 0.81) and the Lassen-corrected (r = 0.79) HMPAO SPECT data showed good correlation with the PET rCBF data. The relationship between the normalized HMPAO SPECT data and the PET data was nonlinear. It is not yet possible to obtain rCBF values in absolute units from HMPAO SPECT without knowledge of the true rCBF in one reference region for each patient.

Topics: Aged; Alzheimer Disease; Carbon Dioxide; Carbon Radioisotopes; Cerebrovascular Circulation; Dementia, Multi-Infarct; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

Single-photon emission computed tomography (SPECT) of the brain using hexamethyl propylene amine oxime (HMPAO) was performed in a 37-year-old patient suffering from mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Reduced blood flow was observed bilaterally in the parieto-occipital regions (resembling Alzheimer type dementia) and in the right parietal lobe.

Topics: Acidosis, Lactic; Adult; Alzheimer Disease; Brain Diseases; Cerebrovascular Disorders; Diagnosis, Differential; Humans; Male; Mitochondria, Muscle; Organotechnetium Compounds; Oximes; Syndrome; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Patients with a clinical diagnosis of Alzheimer's disease were studied using MRI, SPECT, and psychometric tests. Significant correlations between focal perfusion deficits and focal cognitive deficits were found. Significant correlations between regional relaxation time of white matter and psychometric tests of diffuse and focal categories were also found. Pathological examination confirmed Alzheimer's disease as the only diagnosis.

Topics: Aged; Alzheimer Disease; Amphetamines; Blood Flow Velocity; Brain; Cerebral Arteries; Cerebral Cortex; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Organotechnetium Compounds; Oximes; Psychometrics; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

An interactive computer program has been developed to align a three-dimensional region of interest (ROI) model to technetium-99m-hexamethylpropylenamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) studies of the brain. The ROI model subdivides the human brain into fourteen discrete regions. A study was performed to determine normal ranges for HMPAO uptake in the ROIs defined by the model, and to assess the relative interobserver variability using the fitting program. HMPAO SPECT studies of twelve normal volunteers were independently analyzed by four observers. Small but significant differences between operators occurred primarily because of difficulty in defining the angle of the orbitomeatal plane on sagittal SPECT images. Despite this difficulty, the program and model have proven useful in defining ranges for normal cerebral perfusion in a healthy adult population. A study of a small group of patients with Alzheimer's dementia suggests that this procedure may be of use in the diagnosis of this disease.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Brain; Cerebrovascular Circulation; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Organotechnetium Compounds; Oximes; Reference Values; Software; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Thirty-four demented patients, 19 with Alzheimer's and 15 with multi-infarct dementia, were studied using single photon emission computed tomography, and 99mTc-hexamethyl-propylenemine oxime as a tracer of regional cerebral perfusion. Tracer activity ratios, determined in cortical and subcortical regions, were compared with those of 11 age-matched controls. In both groups of demented patients, most of the cortical regions showed significant declines in tracer uptake from control values, with the greatest reductions in the parietal cortex. Significantly lower parietal indexes were found in the Alzheimer's patient group as compared both to the control values and to the group of multi-infarct dementia patients. A positive correlation was found between the magnitude of the parietal deficits and the severity of dementia.

Topics: Aged; Alzheimer Disease; Basal Ganglia; Brain; Cerebral Cortex; Dementia, Multi-Infarct; Dominance, Cerebral; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Organotechnetium Compounds; Oximes; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Single photon emission computed tomography (SPECT) with 99mTc-HMPAO was used to image 26 patients with dementia of the Alzheimer type (DAT) and 10 healthy controls. Regional cerebral blood flow (rCBF) data indicated a relative sparing of the occipital regions in DAT. Normalisation to occipital flow illustrated highly significant CBF deficits in a number of cortical regions, particularly in the left and right posterior--temporal cortex in DAT compared to controls. The cognitive performance of DAT patients was measured using a clinical cognitive assessment procedure (CAMCOG) and numerous correlations between these scores and rCBF were obtained. The implications and value of this investigative technique are discussed.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Dominance, Cerebral; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, X-Ray Computed

Twenty patients satisfying standard clinical criteria for Alzheimer's disease (AD) and six age-matched normal controls were studied using 99mTc hexamethyl-propyleneamine oxime and single photon emission tomography. The AD patients had lower regional cerebral blood flow (rCBF) in the temporal and posterior parietal lobes compared to controls. AD patients with apraxia and aphasia had lower rCBF in the lateral temporal and posterior parietal lobes than AD patients without these features. Within the AD group, correlations were found between neuropsychological tests and rCBF: praxis correlated with posterior parietal activity, memory with left temporal lobe activity and language with activity throughout the left hemisphere.

Topics: Aged; Alzheimer Disease; Aphasia; Apraxias; Brain; Cerebrovascular Circulation; Dominance, Cerebral; Humans; Mental Recall; Neuropsychological Tests; Organometallic Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed

Topics: Alzheimer Disease; Cerebral Cortex; Cerebrovascular Circulation; Dementia; Dementia, Multi-Infarct; Humans; Huntington Disease; Organotechnetium Compounds; Oximes; Parkinson Disease; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Single photon emission tomography (SPET) with the lipophilic blood flow marker 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO) has been used to determine regional uptake of radiolabel into brain regions of patients with presenile Alzheimer's disease and Korsakoff's psychosis, and age-matched controls. Using occipital cortical uptake as reference area, the pattern of relative regional cerebral blood flow (rCBF) was determined in other cortical areas and basal ganglia. In Alzheimer's disease, reduction in rCBF occurred most strikingly in posterior temporal and parietal areas. By contrast, in Korsakoff's psychosis, posterior temporal rCBF was maintained, although there was a trend to reduced tracer uptake in other cortical areas. These impairments of flow were correlated with impairments of neuropsychological function. In Alzheimer's disease, left posterior temporal and left parietal regions in particular showed rCBF to be strongly correlated with most aspects of cognitive function. In Korsakoff's psychosis, however, impaired flow in frontal regions was correlated with impaired performance on tests of memory and orientation. The findings in Alzheimer's disease show quantitative parallels with those from studies using Positron Emission Tomography (PET), and extend our understanding of the relationship between cognition and regional brain function in dementia. The findings in Korsakoff's psychosis offer the first direct evidence linking frontal lobe dysfunction with the cognitive impairment seen in the disorder.

Topics: Adult; Aged; Alcohol Amnestic Disorder; Alzheimer Disease; Basal Ganglia; Cerebral Cortex; Cerebrovascular Circulation; Cognition; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Topics: Aged; Alzheimer Disease; Cerebellum; Cerebral Cortex; Cerebrovascular Circulation; Humans; Neuropsychological Tests; Organotechnetium Compounds; Oximes; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Topics: Aged; Alzheimer Disease; Blood Flow Velocity; Brain; Cerebral Cortex; Dominance, Cerebral; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Organometallic Compounds; Oximes; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed; Xenon Radioisotopes

The acute effects of intravenously administered L-acetylcarnitine (LAC) were evaluated with single-photon emission computed tomography (SPECT) and 99mTc-hexamethylpropyleneamine oxime in 30 demented patients (21 with a clinical diagnosis of Alzheimer's dementia and 9 with mixed-type dementia). Two SPECT scans were performed: in basal conditions, and 30 min after the administration of 500, 1,000, 1,500, or 2,000 mg LAC intravenously. Tracer activity ratios were determined in 10 pairs of cerebellar, cortical and subcortical regions. After administration of the lowest dose of LAC, no changes from the basal values were observed in any of the regions examined. The higher doses of the drug significantly elevated the tracer activity in cortical regions, particularly in the parietal lobe, which showed an impaired regional cerebral blood flow in the basal study. These effects of LAC and their relation with the cholinomimetic properties of the drug are discussed.

Topics: Acetylcarnitine; Aged; Alzheimer Disease; Carnitine; Dementia; Female; Humans; Injections, Intravenous; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed

Single photon emission tomography with Hm PAO Tc99m was used in 27 patients with probable Alzheimer's disease, 9 patients with multi-infarct, dementia, and 11 healthy volunteers. The data were quantified in 4 regions of interest (using the basal ganglia as an internal standard): left and right prefrontal areas (Fg and Fd), and left and right parietal areas (Pg and Pd). Pg and Pd indices were lower in patients with Alzheimer's disease than in patients with multi-infarct dementia, and healthy volunteers (p less than 0.05). The ratio (Fd + Pd)/(Fg + Pg) was lower in patients with dressing apraxia (p less than 0.02), anosognosia (p less than 0.001), spatial agnosia (p less than 0.01), ideomotor apraxia (p less than 0.02), ideatory apraxia (p less than 0.01), and constructive apraxia (p less than 0.01). No correlation could be established between this ratio and the severity of aphasia, or between the indices and mini mental state scores. With Pg and Pd indices lower than 0.90, sensitivity for Alzheimer's disease was 70 p. 100 and specificity, 75 p. 100.

Topics: Aged; Alzheimer Disease; Data Interpretation, Statistical; Dementia, Multi-Infarct; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Predictive Value of Tests; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

A new radiotracer of cerebral perfusion, 99mTc-labelled hexamethylpropylene amine-oxime, has been tried in 78 subjects: 6 controls and 72 patients. Qualitatively, the distribution of this tracer in healthy subjects was very much the same as that obtained with a reference method using 133xenon inhalation. Quantitatively, there was no correlation between the real blood flow rate and the normalized cerebral uptake rate. On the other hand, the asymmetry indices obtained in controls (but also in 16 patients) correlated very closely with those obtained with 133xenon. Our first results in acute ischaemic diseases as well as in the evaluation of vasospasm or Alzheimer-like presenile dementia point to wide fields of application for the new compound. Unlike its predecessors, it is always available and will probably be used, without any logistic investment, with the standard equipment of all Nuclear medicine departments.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Brain Ischemia; Cerebral Hemorrhage; Cerebrovascular Circulation; Cerebrovascular Disorders; Female; Hematoma; Humans; Ischemic Attack, Transient; Male; Middle Aged; Organometallic Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed

One hundred fourteen patients suffering from neuropsychiatric conditions have been studied using 99mTc-labeled hexamethylpropyleneamine oxime (HM-PAO) and single photon emission computed tomography (SPECT). Ninety-one patients had a firm clinical diagnosis while 23 were examined without knowledge of the clinical diagnosis. Of the 91 patients, 51 were suffering from dementia, 25 multi-infarct type and 26 Alzheimer's disease. In 19 of the Alzheimer's patients, a characteristic pattern of decreased perfusion in the parieto-occipital regions was demonstrated while those with multi-infarct type showed varying degrees of irregular uptake in the cerebral cortex. These appearances are similar to those shown with positron emission tomography (PET) and we believe that HM-PAO will provide a widely available method for identifying patients with Alzheimer's disease. Twenty-nine patients were suffering from diseases involving the basal ganglia. Fifteen patients with Parkinson's disease showed no significant abnormality in basal ganglia uptake, while 7 or 8 patients with Huntington's disease who had full examinations showed decreased uptake in the caudate nuclei. Similarly, four of six patients with other basal ganglia diseases showed impaired uptake by basal ganglia, and it is concluded that HM-PAO may be useful for the diagnosis and management of this type of patient. Twenty-three patients received HM-PAO imaging as part of their diagnostic work-up; in 19 of them, detailed follow-up was obtained, which indicated that in 7 cases the result of the HM-PAO scan altered the clinical diagnosis and in 9 cases resulted in a change in management. In the remaining 13 cases, the study was found to be helpful in confirming the diagnosis.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Basal Ganglia Diseases; Brain; Dementia; Female; Humans; Huntington Disease; Male; Middle Aged; Organometallic Compounds; Oximes; Parkinson Disease; Radionuclide Imaging; Technetium; Technetium Tc 99m Exametazime

Eleven patients with Alzheimer type dementia were investigated by single-photon-emission computed tomography (SPECT) using 99mTc-hexamethylpropylene-aminoxim (HM-PAO). Nine had a typical, symmetrically reduced enrichment in the parieto-temporo-occipital area. In three of these nine patients a similar pattern was recorded additionally in the frontal, in the remaining two in the temporal or parietal region. In a semi-quantitative evaluation radioactivity concentrations in the cerebrum and cerebellum were compared. It demonstrated that there was in relation to the cerebellum a reduced concentration in seven of the eight studied cerebral regions. The relative blood flow of the parieto-temporo-occipital region was most markedly affected and in patients with Alzheimer type dementia was reduced by 25% below that of normal subjects. The results indicate that cerebral SPECT with HM-PAO is a reasonable method of investigation to confirm the diagnosis of "Alzheimer type dementia" and exclude other cerebral disease, especially if pathognomonic findings are to be obtained.

Topics: Alzheimer Disease; Brain; Cerebrovascular Circulation; Diagnosis, Differential; Humans; Middle Aged; Organometallic Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed; Tomography, X-Ray Computed

Regional cerebral perfusion was evaluated by single photon emission computed tomography (SPECT) using technetium-99m hexamethylpropyleneamine oxime ([99mTc]HM-PAO) in sixteen patients with Alzheimer's disease (AD) in early clinical phase and in 16 healthy elderly controls. In all patients transmission computed tomography (TCT) and/or magnetic resonance imaging (MRI) did not show focal brain abnormalities. Relative to normal subjects, AD patients showed significant reductions in cortical/cerebellar activity ratio: cortical perfusion was globally depressed with the largest reductions in frontal and posterior temporo-parietal cortices. Asymmetries of relative perfusion between cerebral hemispheres were also demonstrated when language was affected or visuospatial functions were unevenly impaired. In patients with early AD, SPECT provides functional information to be compared with clinical and psychometric data.

Topics: Aged; Alzheimer Disease; Brain; Cerebrovascular Circulation; Female; Humans; Male; Middle Aged; Organometallic Compounds; Oximes; Technetium; Technetium Tc 99m Exametazime; Tomography, Emission-Computed

We present preliminary data on the utility of functional brain imaging with [99mTc]-d,l-HM-PAO and single photon emission computed tomography (SPECT) in the study of patients with dementia of the Alzheimer type (DAT), HIV-related dementia syndrome, and the "on-off" syndrome of Parkinson's disease. In comparison with a group of age-matched controls, the DAT patients revealed distinctive bilateral temporal and posterior parietal deficits, which correlate with detailed psychometric evaluation. Patients with amnesia as the main symptom (group A) showed bilateral mesial temporal lobe perfusion deficits (p less than 0.02). More severely affected patients (group B) with significant apraxia, aphasia, or agnosia exhibited patterns compatible with bilateral reduced perfusion in the posterior parietal cortex, as well as reduced perfusion to both temporal lobes, different from the patients of the control group (p less than 0.05). SPECT studies of HIV patients with no evidence of intracraneal space occupying pathology showed marked perfusion deficits. Patients with Parkinson's disease and the "on-off" syndrome studied during an "on" phase (under levodopa therapy) and on another occasion after withdrawal of levodopa ("off") demonstrated a significant change in the uptake of [99mTc]-d,l-HM-PAO in the caudate nucleus (lower on "off") and thalamus (higher on "off"). These findings justify the present interest in the functional evaluation of the brain of patients with dementia. [99mTc]-d,l-HM-PAO and regional cerebral blood flow (rCBF)/SPECT appear useful and highlight individual disorders of flow in a variety of neuropsychiatric conditions.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Alzheimer Disease; Brain; Cerebrovascular Circulation; Dementia; Female; Humans; Male; Middle Aged; Organometallic Compounds; Oximes; Parkinson Disease; Technetium; Technetium Tc 99m Exametazime; Tomography, Emission-Computed

SPECT images of the brain can be obtained using either 123I labelled amines or 99mTc-hexamethylpropyleneamineoxime (HM-PAO). Both materials produce images which are blood flow dominated and so appear similar in normal subjects, although the respective mechanisms of uptake are not yet finally established. It seems likely, however, that the different mechanisms of uptake are responsible for recent reports of some differences seen in images obtained with the two types of agent in patients with cerebral pathology, mainly cerebrovascular disease. In this study, 12 demented patients, 6 with dementia of the Alzheimer type (DAT) and 6 with multi infarct dementia (MID), were imaged with 123I-isopropylamphetamine (IMP) and 99mTc-HM-PAO and the images compared. Significantly more lesions were seen with IMP than HM-PAO (P less than 0.02); out of a possible 120 sites, 41 lesions were seen with IMP compared to 28 with HM-PAO, 23 being seen with both agents. However, it is concluded that either agent can be used for the differential diagnosis of dementia, a task for which the new cerebral blood flow agents seem well suited.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amphetamines; Brain; Dementia, Multi-Infarct; Humans; Iodine Radioisotopes; Iofetamine; Middle Aged; Organometallic Compounds; Oximes; Technetium; Technetium Tc 99m Exametazime; Tomography, Emission-Computed

Topics: Alzheimer Disease; Brain; Dementia; Humans; Huntington Disease; Ischemic Attack, Transient; Organometallic Compounds; Oximes; Radionuclide Imaging; Technetium Tc 99m Exametazime

Single photon emission tomographic imaging of the brain using 99mTc HM-PAO was carried out in patients with a clinical diagnosis of Alzheimer's disease, non-Alzheimer frontal-lobe dementia, and progressive supranuclear palsy. Independent assessment of reductions in uptake revealed posterior hemisphere abnormalities in the majority of the Alzheimer group, and selective anterior hemisphere abnormalities in both other groups. The findings were consistent with observed patterns of mental impairment. The imaging technique has potential value in the differential diagnosis of primary cerebral atrophy.

Topics: Aged; Alzheimer Disease; Atrophy; Brain Ischemia; Dementia; Dominance, Cerebral; Female; Frontal Lobe; Humans; Male; Middle Aged; Organometallic Compounds; Oximes; Supranuclear Palsy, Progressive; Technetium Tc 99m Exametazime; Tomography, Emission-Computed