2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane and Dementia

To systematically review the utility of dopamine system imaging using 123I-FP-CIT SPECT in the differential diagnosis between dementia with Lewy bodies (DLB) and other dementia syndromes.. We searched MEDLINE, CENTRAL and ClinicalTrials.gov to identify studies reporting enough data to determine accuracy measure of 123I-FP-CIT SPECT in differentiating between DLB and other dementia syndromes. Studies including patients with Parkinson's disease or other parkinsonisms associated with abnormal DAT imaging were excluded. The methodological quality of studies was evaluated with QUADAS-2.. Eight studies were included. Studies adopting a clinical diagnosis as a reference standard showed sensitivity and specificity values of DaTSCAN in differentiating between DLB and non-DLB dementia syndromes (all subtypes, AD and FTD) consistently higher than 80%, both considering a visual and a semiquantitative analysis. The meta-analyses from the three studies using a neuropathological reference standard yielded sensitivity and specificity values higher than those adopting a clinical diagnostic reference.. 123I-FP-CIT SPECT can represent an accurate method to differentiate between DLB and other dementia syndromes. However, most data in the literature derive from studies adopting the clinical diagnosis as the reference diagnostic standard and which are therefore intrinsically unable to demonstrate an accuracy of DAT imaging above that of careful clinical diagnosis alone. The very few studies providing information on the neuropathologic correlation for the DaTSCAN findings show however high sensitivity and specificity values, suggesting that SPECT scan is more accurate than clinical diagnosis and may prove useful in supporting the clinical diagnosis of DLB.

Topics: Dementia; Diagnosis, Differential; Humans; Lewy Body Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

This review article is focused upon the most recent biomarker studies of Parkinson's disease. It provides an update on promising areas of biomarker research in a rapidly expanding field, and discusses future directions that might lead to successful development of Parkinson's disease biomarkers.. Studies of molecular-genetic and biochemical biomarkers of Parkinson's disease have not only targeted hypothesis-driven measures of specific substrates involved in processes such as protein misprocessing, but also have made use of sophisticated analyses such as transcriptomic, proteomic, and metabolomic approaches. Whereas none of these are yet established as Parkinson's disease biomarkers, brain imaging using the 123I-ioflupane ligand with single-photon emission computed tomography was recently approved in the United States to aid in Parkinson's disease diagnosis, and research on other imaging modalities is ongoing. Neurophysiological tests are also being adapted for biomarker research, and we review recent promising data.. The search for effective biomarkers for diagnosis and surveillance of Parkinson's disease continues. A battery of biomarkers comprising different modalities might be required to address clinical needs in this complex disorder. Critically, collaborative efforts including centralized tissue repository and clinical research infrastructure that are being organized will advance this field further.

Topics: alpha-Synuclein; Animals; Biomarkers; Dementia; Humans; MicroRNAs; Neurophysiology; Nortropanes; Parkinson Disease; Tomography, Emission-Computed, Single-Photon

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Topics: Alzheimer Disease; Dementia; Humans; Image Processing, Computer-Assisted; Movement Disorders; Nortropanes; Observer Variation; Parkinsonian Disorders; Radiopharmaceuticals; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon

The objective of this study was to investigate the rate of progression of nigrostriatal dopaminergic loss in subjects with dementia with Lewy bodies (DLB), Parkinson's disease (PD) and PD with dementia (PDD) using serial 123I-FP-CIT SPECT imaging. We hypothesised that striatal rates of decline in patients would be greater than in controls, and that DLB and PDD would show similar rates, reflecting the similarity in neurobiological mechanisms of dopaminergic loss between the two disorders.. We studied 20 patients with DLB, 20 with PD, 15 with PDD and 22 healthy age-matched controls. Semi-automated region of interest (ROI) analysis was performed on both baseline and repeat scans for each subject and mean striatal uptake ratios (caudate, anterior and posterior putamen) were calculated.. Rates of decline in striatal binding between groups were assessed using ANCOVA. Significant differences between patients and controls were observed in caudate (DLB, PD, PDD, p< or =0.01), anterior putamen (DLB, PDD, p< or =0.05; PD, p=0.07) and posterior putamen (DLB, PD, PDD, p<0.006). Rates of decline were similar between DLB, PD and PDD.. In conclusion, this is the first study to show that significant progressive dopaminergic loss occurs in DLB and PDD using serial 123I-FP-CIT SPECT. Dementia severity and motor impairment were correlated with decline, suggesting that dopaminergic loss may play an important role in cognitive as well as motor features.

Topics: Aged; Corpus Striatum; Dementia; Disease Progression; Dopamine; Female; Humans; Lewy Body Disease; Male; Parkinson Disease; Radiopharmaceuticals; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes

To investigate whether the cingulate island sign (CIS) ratio (i.e., the ratio of regional uptake in the posterior cingulate cortex relative to the precuneus and cuneus on cerebral perfusion scans) is associated with early dementia conversion in Parkinson's disease (PD).. We enrolled 226 patients with newly diagnosed PD and 48 healthy controls who underwent dual-phase. There were no significant differences in age, sex, education, or baseline cognitive function between the PD groups. The PD-CIS group had higher Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and more severely decreased dopamine transporter availability in the putamen. The PD-iCIS group had a smaller hippocampal volume compared with the other groups. The risk of dementia conversion in the PD-CIS group did not differ from that in the PD-iCIS and PD-nCIS groups. Meanwhile, the PD-iCIS group had a higher risk of dementia conversion than the PD-nCIS group.. The results of this study suggest that inverse CIS, rather than CIS, is relevant to early dementia conversion in patients with PD.

Topics: Dementia; Humans; Parkinson Disease; Positron-Emission Tomography; Tropanes

Aging is the most important risk factor of development of dementia in Parkinson's disease (PD), but there are no data on clinical and radiological heterogeneity of PD dementia (PDD) depending on age at onset.. The goal of this study was to examine whether patients with PDD are clinically and radiologically heterogeneous depending on age at onset.. A total of 116 patients with PD dementia and 121 age- and sex-matched normal controls were enrolled. The subjects were divided into early-onset (EOPDD; n = 39) and late-onset (LOPDD; n = 77) PDD with the respective age-matched control group based on a cutoff value of 70 years. The effects of diagnosis, age, and their interaction on neuropsychological tests, cortical thickness, and substantia innominata volume were assessed using analysis of covariance.. EOPDD patients had a poorer cognitive performance on digit backward, forward span test (p = 0.011 and 0.05), and visual recognition memory function (p = 0.012) compared with LOPDD patients. Additionally, EOPDD patients exhibited cortical thinning in the left anterior cingulate gyrus and the right inferior temporal gyrus, with significantly decreased normalized substantia innominata volume (p = 0.044).. Our data demonstrated that EOPDD patients exhibit poorer cognitive performance and more severe atrophy in the cortex and substantia innominata, implying that EOPDD may be a distinct phenotype different from LOPDD.

Topics: Age of Onset; Aged; Case-Control Studies; Cerebral Cortex; Cognition Disorders; Dementia; Female; Fluorine Radioisotopes; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Statistics, Nonparametric; Tropanes

Establishing an early, accurate diagnosis is fundamental for appropriate clinical management of patients with movement disorders or dementia. Ioflupane (123)I Injection (DaTscan, (123)I-ioflupane) is an important adjunct to support the clinical diagnosis. Understanding individual-reader diagnostic performance of (123)I-ioflupane in a variety of clinical scenarios is essential.. Sensitivity, specificity, interreader, and intrareader data from 5 multicenter clinical studies were reviewed. The different study designs offered an assortment of variables to assess the effects on the diagnostic performance of (123)I-ioflupane: on-site versus 3-5 blinded image readers, number of image evaluations, early/uncertain versus late/confirmed clinical diagnosis as reference standard, and subjects with movement disorders versus dementia.. Eight hundred eighteen subjects had individual-reader efficacy data available for analysis. In general, sensitivity and specificity were high and comparable between on-site versus blinded independent readers. In subjects with dementia, when the clinical diagnosis was made at month 12 versus baseline, specificity improved from 77.4%-91.2% to 81.6%-95.0%. In subjects with movement disorders, this effect was observed to an even greater extent, when diagnostic performance using month-18 diagnosis as a reference standard (sensitivity, 67.0%-73.7%; specificity, 75.0%-83.3%) was compared versus month-36 diagnosis (77.5%-80.3% and 90.3%-96.8%, respectively). Diagnostic performance was similar in subjects with dementia (74.4%-89.9% and 77.4%-95.0%, respectively) and subjects with movement disorders (67.0%-97.9% and 71.4%-98.4%, respectively). In most of the comparisons, between-reader agreement was very good (almost perfect), with κ ranging from 0.81 to 1.00. Within-reader agreement, measured in 1 study, was 100% for 3 blinded readers.. Individual-reader diagnostic performance, as assessed by measuring sensitivity and specificity of (123)I-ioflupane to detect the presence or absence of striatal dopaminergic deficit, using the clinical diagnosis as a reference standard, was high in subjects with either movement disorders or dementia and was similar in on-site readers versus blinded analyses. Between- and within-reader agreements were very good (almost perfect). Longer follow-up between imaging and clinical diagnosis improved the diagnostic accuracy, most likely due to improvement in the clinical diagnosis reference standard, rather than changes in reader accuracy.

Topics: Adult; Aged; Aged, 80 and over; Clinical Trials as Topic; Dementia; Female; Follow-Up Studies; Humans; Injections; Male; Middle Aged; Multicenter Studies as Topic; Nortropanes; Observer Variation; Parkinsonian Disorders; Sensitivity and Specificity; Time Factors; Tomography, Emission-Computed, Single-Photon; Young Adult

To pool clinical trials of similar design to assess overall sensitivity and specificity of ioflupane I123 injection (DaTSCAN or ioflupane ((123)I)) to detect or exclude a striatal dopaminergic deficit disorder (SDDD), such as parkinsonian syndrome and dementia with Lewy bodies.. Pooled analysis of three phase 3 and one phase 4 clinical trials. These four trials were selected because they were the four studies used for the US new drug application to the Food and Drug Administration (FDA).. Multicentre, open-label, non-randomised.. Patients with either a movement disorder or dementia, and healthy volunteers.. Ioflupane ((123)I) was administered.. Images were assessed by panels of 3-5 blinded experts and/or on-site nuclear medicine physicians, classified as normal or abnormal and compared with clinical diagnosis (reference standard) to determine sensitivity and specificity.. Pooling the four studies, 928 participants were enrolled, 849 were dosed and 764 completed their study. Across all studies, when images were assessed by on-site readers, ioflupane ((123)I) diagnostic effectiveness had an overall (95% CI) sensitivity of 91.9% (88.7% to 94.5%) and specificity of 83.6% (78.7% to 87.9%). When reads were conducted blindly by a panel of independent experts, the overall sensitivity was 88.7% (86.8% to 90.4%) and specificity was 91.2% (89.0% to 93.0%).. In this pooled analysis, the visual assessment of ioflupane ((123)I) images provided high levels of sensitivity and specificity in detecting the presence/absence of an SDDD. Ioflupane ((123)I) imaging has the potential to improve diagnostic accuracy in patients with signs and symptoms of a movement disorder and/or dementia.. NCT00209456.

Topics: Adult; Aged; Aged, 80 and over; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Dementia; Female; Humans; Injections; Iodine Radioisotopes; Male; Middle Aged; Movement Disorders; Nortropanes; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity

Dopamine transporter (DAT) imaging with [(123)I]FP-CIT (DaTSCAN) is an established diagnostic tool in parkinsonism and dementia. Although qualitative assessment criteria are available, DAT quantification is important for research and for completion of a diagnostic evaluation. One critical aspect of quantification is the availability of normative data, considering possible age and gender effects on DAT availability. The aim of the European Normal Control Database of DaTSCAN (ENC-DAT) study was to generate a large database of [(123)I]FP-CIT SPECT scans in healthy controls.. SPECT data from 139 healthy controls (74 men, 65 women; age range 20-83 years, mean 53 years) acquired in 13 different centres were included. Images were reconstructed using the ordered-subset expectation-maximization algorithm without correction (NOACSC), with attenuation correction (AC), and with both attenuation and scatter correction using the triple-energy window method (ACSC). Region-of-interest analysis was performed using the BRASS software (caudate and putamen), and the Southampton method (striatum). The outcome measure was the specific binding ratio (SBR).. A significant effect of age on SBR was found for all data. Gender had a significant effect on SBR in the caudate and putamen for the NOACSC and AC data, and only in the left caudate for the ACSC data (BRASS method). Significant effects of age and gender on striatal SBR were observed for all data analysed with the Southampton method. Overall, there was a significant age-related decline in SBR of between 4 % and 6.7 % per decade.. This study provides a large database of [(123)I]FP-CIT SPECT scans in healthy controls across a wide age range and with balanced gender representation. Higher DAT availability was found in women than in men. An average age-related decline in DAT availability of 5.5 % per decade was found for both genders, in agreement with previous reports. The data collected in this study may serve as a reference database for nuclear medicine centres and for clinical trials using [(123)I]FP-CIT SPECT as the imaging marker.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Brain; Brain Mapping; Calibration; Case-Control Studies; Databases, Factual; Dementia; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Models, Statistical; Nuclear Medicine; Parkinsonian Disorders; Reference Values; Sex Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

There is still a need for simple, noninvasive, and inexpensive methods to diagnose the causes of cognitive impairment and dementia. In this study, contemporary statistical methods were used to classify the clinical cases of cognitive impairment based on electroencephalograms (EEG).. An EEG database was established from seven different groups of subjects with cognitive impairment and dementia as well as healthy controls. A classifier was created for each possible pair of groups using statistical pattern recognition (SPR).. A good-to-excellent separation was found when differentiating cases of degenerative disorders from controls, vascular disorders, and depression but this was less so when the likelihood of comorbidity was high.. Using EEG with SPR seems to be a reliable method for diagnosing the causes of cognitive impairment and dementia, but comorbidity must be taken into account.

Topics: Aged; Aged, 80 and over; Area Under Curve; Cognitive Dysfunction; Dementia; Electroencephalography; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multivariate Analysis; Neuropsychological Tests; Nortropanes; Pattern Recognition, Automated; Radiopharmaceuticals; Reproducibility of Results; ROC Curve; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

We performed 123I-FP-CIT/SPECT and ECD/SPECT in 30 patients with Parkinson's disease with dementia (PDD) and 30 patients with dementia with Lewy bodies (DLB) to evaluate whether presynaptic nigro-striatal function and/or cerebral perfusional pattern is different in these diseases. The striatal uptake of DAT tracer was statistically significantly lower in PDD and DLB with respect to control data (p < 0.0005), however no significant difference was found between PDD and DLB. Patients with PDD and DLB showed a significant reduction of rCBF (p < 0.001) in parieto-occipital and frontal areas, with respect to controls, but the comparison between the two groups did not result in any significant difference by SPM analysis. Finally no correlation was found between any regional perfusional changes and nigro-striatal dysfunction. We conclude that neither studies with 123I-FP-CIT nor ECD/SPECT were able to discriminate between DLB and PDD in vivo.

Topics: Aged; Aged, 80 and over; Brain Mapping; Cerebrovascular Circulation; Corpus Striatum; Dementia; Diterpenes, Clerodane; Female; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Parkinson Disease; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Brain; Dementia; Diagnosis, Differential; Diagnostic Imaging; Dopamine; Humans; Lewy Body Disease; Predictive Value of Tests; Tomography, Emission-Computed, Single-Photon; Tropanes

Extrapyramidal symptoms are observed in frontotemporal dementia (FTD). (123)I-FP-CIT (DaT scan) single photon emission computed tomography (SPECT) can detect loss of presynaptic dopamine transporters in the striatum. We aimed to evaluate the dopaminergic status of the striatum in patients with FTD using DaT scan. Seven patients (age range 65-76 years), who fulfilled the Neary criteria and in whom the diagnosis of FTD was confirmed by hexamethylpropyleneamine oxime SPECT, were included in the study. The severity of the extrapyramidal symptoms was evaluated by the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS). SPECT using (123)I-FP-CIT was done. A (region - occipital)/occipital ratio was calculated for the striatum, putamen and caudate nucleus. The results were compared with those of the 7 age-matched normal controls. The uptake of the radiotracer in the right and left striatum was reduced to 62% (p = 0.000) and 68% (p = 0.000), respectively, compared to controls. The motor UPDRS score of the patients with FTD showed a negative correlation to the uptake of the radiotracer. The presynaptic dopamine transporter in FTD is impaired, related to the severity of the extrapyramidal symptoms. Since an effective treatment for FTD is still to be established, there is a need for evaluating the efficacy of dopaminergic drugs.

Topics: Aged; Basal Ganglia Diseases; Brain; Corpus Striatum; Dementia; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Hypokinesia; Male; Muscle Rigidity; Tomography, Emission-Computed, Single-Photon; Tropanes

With the dopaminergic presynaptic ligand FP-CIT and single photon emission tomography we have shown a severe dopaminergic degeneration in a patient with a necropsy confirmed diagnosis of dementia with Lewy bodies (DLB). We suggest that functional imaging of the nigrostriatal dopamine pathway helps to distinguish DLB from Alzheimer's disease during life.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Dementia; Diagnosis, Differential; Dopamine; Humans; Lewy Bodies; Male; Nerve Degeneration; Neurons; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes