2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane and Lewy-Body-Disease

Dopaminergic scintigraphic imaging is a cornerstone to support the diagnosis in dementia with Lewy bodies. To clarify the current state of knowledge on this imaging modality and its impact on clinical diagnosis, we performed an updated systematic review of the literature.. This systematic review was carried out according to PRISMA guidelines. A comprehensive computer literature search of PubMed/MEDLINE, EMBASE, and Cochrane Library databases for studies published through June 2022 was performed using the following search algorithm: (a) "Lewy body" [TI] OR "Lewy bodies" [TI] and (b) ("DaTscan" OR "ioflupane" OR "123ip" OR "123?ip" OR "123 ip" OR "123i-FP-CIT" OR "FPCIT" OR "FP-CIT" OR "beta?CIT" OR "beta CIT" OR "CIT?SPECT" OR "CIT SPECT" OR "Dat?scan*" OR "dat scan*" OR "dat?spect*" OR "SPECT"). Risk of bias and applicability concerns of the studies were evaluated using the QUADAS-2 tool.. We performed a qualitative analysis of 59 studies. Of the 59 studies, 19 (32%) addressed the diagnostic performance of dopamine transporter imaging, 15 (25%) assessed the identification of dementia with Lewy bodies in the spectrum of Lewy body disease and 18 (31%) investigated the role of functional dopaminergic imaging in distinguishing dementia with Lewy bodies from other dementias. Dopamine transporter loss was correlated with clinical outcomes in 19 studies (32%) and with other functional imaging modalities in 15 studies (25%). Heterogeneous technical aspects were found among the studies through the use of various radioligands, the more prevalent being the [123I]N‑ω‑fluoropropyl‑2β‑carbomethoxy‑3β‑(4‑iodophenyl) nortropane (. Our systematic review confirms the major role of dopaminergic scintigraphic imaging in the assessment of dementia with Lewy bodies. Early diagnosis could be facilitated by identifying the prodromes of dementia with Lewy bodies using dopaminergic scintigraphic imaging coupled with emphasis on clinical neuropsychiatric symptoms. Most published studies use a semi-quantitative analytical assessment of tracer uptake, while there are no studies using quantitative analytical methods to measure dopamine transporter loss. The superiority of a purely quantitative approach to assess dopaminergic transmission more accurately needs to be further clarified.

Topics: Dopamine Plasma Membrane Transport Proteins; Humans; Iodine Radioisotopes; Lewy Body Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

The 123I-FP-CIT dopamine transporter SPECT imaging is a sensitive method to assess functional dopaminergic neuron terminals in the striatum. The method has also been available in Hungary for years. There are two main indications: (i) to help differentiate essential tremor from clinically uncertain Parkinsonism, including patients with early symptoms and (ii) to help differentiate dementia with Lewy bodies from Alzheimer's disease. The aim of this paper is to review 123I-FP-CIT SPECT imaging based on international data/guidelines and our own experiences, thereby assisting nuclear medicine practitioners and neurologists.. A 123I-FP-CIT dopamintranszporter SPECT-képalkotás egy érzékeny módszer a működőképes striatalis dopaminerg idegvégződések működésének megítélésére. A módszer évek óta Magyarországon is elérhető. Két fő indikációja az 1. klinikailag bizonytalan, vagy korai tüneteket produkáló parkinsonizmus és az esszenciális tremor elkülönítése, valamint a 2. Lewy-testes dementiának az Alzheimer-kórtól való megkülönböztetése. A jelen összefoglaló célja, hogy a nemzetközi adatok és ajánlások, valamint saját tapasztalatok alapján bemutassa a 123I-FP-CIT SPECT-képalkotást, ezzel segítve a gyakorló nukleáris medicina szakemberek és a neurológusok munkáját.

Topics: Alzheimer Disease; Dopamine Plasma Membrane Transport Proteins; Humans; Hungary; Lewy Body Disease; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

The use of biomarkers (BMs) for accurate diagnosis of Alzheimer's disease (AD) has been proposed by recent diagnostic criteria; however, their maturity is not sufficient to grant implementation in the clinical routine. A proper diagnostic process requires not only confirmation of the disease but also the exclusion of similar disorders entering differential diagnosis, like dementia with Lewy bodies (DLB). This review is aimed at evaluating the clinical validity of

Topics: 3-Iodobenzylguanidine; Alzheimer Disease; Biomarkers; Cognitive Dysfunction; Diagnosis, Differential; Heart; Humans; Iodine Radioisotopes; Lewy Body Disease; Nortropanes; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon

Dementia with Lewy bodies (DLB) is a common cause of neurodegenerative dementia of old age. Its accurate recognition can be important in clinical management and is essential for the development of disease-modifying treatments. The current clinical diagnostic criteria are limited particularly by relatively poor sensitivity. Dopamine transporter (DAT) imaging using single-photon emission computed tomography (SPECT) is the most highly developed supplementary test for DLB, and is now incorporated as a suggestive feature in the consensus diagnostic criteria. However, there is uncertainty about its accuracy and its place in clinical practice. It is most commonly used in people who are already suspected of having DLB.. We had two objectives in this review: (A) to estimate the accuracy of DAT imaging for the diagnosis of DLB in people with dementia in secondary care (specialist dementia services), and (B) to estimate the accuracy of DAT imaging for the diagnosis of DLB in people with dementia in secondary care who are already suspected of having DLB on the basis of a prior clinical work-up.. We searched MEDLINE (1946 to February 2013), Embase (1980 to February 2013), BIOSIS Previews (1926 to February 2013), PsycINFO (1806 to February 2013), CINAHL (1982 to February 2013), LILACS (February 2013) and Web of Science and Conference Proceedings (ISI Web of Science) (1945 to February 2013). Several of these sources contain conference abstracts. We also searched four specialised databases containing diagnostic reviews: Meta-analyses van Diagnostisch Onderzoek (MEDION; February 2013), Database of Abstracts of Reviews of Effects (DARE; February 2013), Health Technology Assessment Database (HTA; February 2013), and Aggressive Research Intelligence Facility (ARIF; February 2013). We checked reference lists of relevant studies and reviews for potential additional studies. Terms for electronic database searching were devised in conjunction with the team at the Cochrane Dementia and Cognitive Improvement Group.. We included test accuracy studies with delayed verification, diagnostic case-control studies, and two-gate studies with alternative diagnosis controls.. (A) participants with dementia in secondary care, (B) participants in secondary care meeting consensus clinical criteria (other than the DAT imaging criterion) for possible or probable DLB, or both.. SPECT or positron emission tomography (PET) imaging of brain dopamine transporters. Reference standard: Neuropathological diagnosis at autopsy.. Two review authors independently selected studies for inclusion and extracted data. We extracted results into a 2x2 table, showing the binary test results cross-classified with the binary reference standard. We used this data to calculate sensitivities, specificities, and their 95% confidence intervals. We used the QUADAS-2 tool plus some additional items to assess methodological quality.. We included one study that was applicable to our first objective (A). It reported data on 22 participants who met consensus clinical criteria for DLB or National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for Alzheimer's disease, or both (a two-gate design with alternative diagnosis controls). The index test was SPECT scanning using the ligand (123)I-FP-CIT. We considered the study to be at high risk of bias in the participant selection and index test domains (QUADAS-2). (123)I-FP-CIT SPECT analysed semiquantitatively had a sensitivity of 1.00 (95% confidence interval (CI) 0.66 to 1.00) and a specificity of 0.92 (95% CI 0.64 to 1.00) for the diagnosis of DLB (n = 22, 1 study). Analysed visually, the sensitivity was 0.86 (95% CI 0.42 to 1.00) and the specificity was 0.83 (95% CI 0.52 to 0.98) (n = 19, 1 study).We considered that the study also provided the best available data to address our second objective (B). At baseline, 15 participants were clinically suspected of having DLB. In this group, (123)I-FP-CIT SPECT scanning analysed semiquantitatively had a sensitivity of 1.00 (95% CI 0.63 to 1.00) and a specificity of 1.00 (95% CI 0.59 to 1.00) for the diagnosis of DLB (n = 15, 1 study). Analysed visually, accuracy in this group was lower with a sensitivity of 0.83 (95% CI 0.36 to 1.00) and a specificity of 0.71 (95% CI 0.29 to 0.96) (n = 13, 1 study).. Only one study has used a neuropathological reference standard to assess the accuracy of DAT imaging for the diagnosis of DLB. The small size of the included study means that sensitivity and specificity estimates are imprecise. However, data from this study suggest that DAT imaging is more accurate than clinical diagnosis. Clinical diagnosis is therefore unsuitable to use as a reference standard for assessing the accuracy of DAT imaging.No studies using a neuropathological reference standard have directly addressed the common clinical scenario where the use of DAT imaging is considered as a diagnostic test in a person with possible DLB, or assessed the accuracy of DAT imaging in people with mild dementia. However, the data from the included study suggest that, where there is moderately severe dementia and a strong pre-existing suspicion of DLB (probable DLB), then a normal (123)I-FP-CIT SPECT scan may be an accurate means of excluding the diagnosis.Semiquantitative ratings of (123)I-FP-CIT SPECT scans appeared to be more accurate than visual ratings in all analyses.

Topics: Alzheimer Disease; Brain; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Humans; Iodine Radioisotopes; Lewy Body Disease; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

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

A systematic meta-analysis of published studies on the diagnostic accuracy of presynaptic dopaminergic imaging with ¹²³I-FP-CIT (DaTSCAN) in dementia with Lewy bodies (DLB).. We included (a) studies in which DaTSCAN was performed in cases of diagnostic uncertainty to differentiate between DLB and non-DLB dementia and (b) studies of patients with already established diagnoses of DLB, non-DLB dementia, or normalcy, against which the diagnostic accuracy of DaTSCAN was tested. We applied fixed-effects Mantel-Haenszel and hierarchical logistic regression models for meta-analysis of the diagnostic test's accuracy. The pooled sensitivity, specificity and diagnostic odds ratio (DOR) were estimated. Heterogeneity among studies was estimated by calculating the corresponding I² statistic. We tested for publication or other bias by creating the respective funnel plot.. Four studies, with a total of 419 subjects, were judged to be suitable for meta-analysis. According to hierarchical models, the estimated pooled sensitivity of DaTSCAN in differentiating DLB versus no DLB was 86.5% [95% Confidence Intervals (CI): 72-94.1%], the specificity was 93.6% (95% CI: 88.5-96.6%), and the DOR was 94.2 (95% CI: 25.7-345). The Mantel-Haenszel estimate of overall DOR was calculated at 48.95 (95% CI: 26.16-91.59). There was some heterogeneity among studies (I² = 45%), but this was not found statistically significant (χ² test for heterogeneity p value = 0.142). Funnel plot analysis showed no significant bias.. Allowing for the small number of studies in the meta-analysis, our results showed high diagnostic accuracy of DaTSCAN in DLB diagnosis, especially in terms of specificity.

Topics: Dopamine Plasma Membrane Transport Proteins; Humans; Lewy Body Disease; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity; Tropanes

Early, accurate diagnosis of dementia with Lewy bodies (DLB), in particular its differentiation from Alzheimer's disease, is important for optimal management, providing patients/carers with information about the likely symptomatology and illness course, allowing initiation of effective pharmacotherapy, and avoiding the consequences of neuroleptic sensitivity. Clinical diagnosis of DLB has high specificity but low sensitivity. Clinical trials of [(123)I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography ([(123)I]FP-CIT SPECT) indicate high positive and negative percent agreement with reference to clinical diagnosis, and high sensitivity and specificity in patients with neuropathologically confirmed diagnoses of DLB. An abnormal [(123)I]FP-CIT SPECT image in patients fulfilling criteria for possible DLB advances the certainty of a diagnosis to probable DLB. [(123)I]FP-CIT SPECT, by identifying the striatal dopaminergic deficit, can be a valuable diagnostic aid and can provide support to a clinical diagnosis of DLB in patients with dementia. The technique is likely to be of particular utility in patients with dementia with an uncertain diagnosis.

Topics: Alzheimer Disease; Brain; Humans; Lewy Body Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

The clinical diagnostic criteria for dementia with Lewy bodies (DLB) have a low sensitivity, and there are no generally accepted biomarkers to distinguish DLB from other dementias. Our aim was to identify biomarkers that may differentiate DLB from Alzheimer's disease (AD).. We performed a systematic literature search for studies of EEG, imaging techniques and genetic and CSF markers that provide sensitivity and specificity in the identification of DLB.. The best evidence was for scintigraphy of the striatal dopamine transporter system using FP-CIT SPECT. Several small scintigraphy studies of cardiovascular autonomic function using metaiodobenzylguanidine SPECT have reported promising results. Studies exploring innovative techniques based on CSF have reported interesting findings for the combination of amyloid beta (abeta) isoforms as well as alpha-synuclein, and there are interesting results emerging from preliminary studies applying proteomic techniques. Data from studies using structural MRI, perfusion SPECT, genetics and EEG studies show differences between DLB and AD but only at a group level.. Several potential biomarkers for the differential diagnosis of probable DLB and AD have shown good diagnostic accuracy in the research setting. Data from large multicentre studies and from studies with autopsy confirmation exist for scintigraphy of the dopamine transporter system. Future studies should explore its value in possible DLB and for clinical management and health economics.

Topics: Aged; alpha-Synuclein; Alzheimer Disease; Biomarkers; Cognition Disorders; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Early Diagnosis; Electroencephalography; Humans; Iodine Radioisotopes; Lewy Body Disease; Neuropsychological Tests; Phosphorylation; Positron-Emission Tomography; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes; Ubiquitin

Functional imaging of the dopamine transporter (DAT) defines integrity of the dopaminergic system and has its main clinical application in patients with mild, incomplete, or uncertain parkinsonism. Imaging with specific single positron emission computerised tomography ligands for DAT (FP-CIT, beta-CIT, IPT, TRODAT) provides a marker for presynaptic neuronal degeneration. Striatal uptake correlates with disease severity, in particular bradykinesia and rigidity, and monitoring of progression assists in clinical trials of potential neuroprotective drugs. DAT imaging is abnormal in idiopathic Parkinson's disease, multiple system atrophy and progressive supranuclear palsy and does not distinguish between these disorders. Dopamine loss is seen even in the earliest clinical presentations of true parkinsonism; a normal scan suggests an alternative diagnosis such as essential tremor, vascular parkinsonism (unless there is focal basal ganglia infarction), drug-induced parkinsonism, or psychogenic parkinsonism. Congruence between working clinical diagnosis and DAT imaging increases over time in favour of baseline DAT imaging results. Additional applications are characterising dementia with parkinsonian features (abnormal results in dementia with Lewy bodies, normal in Alzheimer's disease); and differentiating juvenile-onset Parkinson's disease (abnormal DAT) from dopa-responsive dystonia (normal DAT).

Topics: Alzheimer Disease; Brain; Cocaine; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Humans; Iodine Radioisotopes; Lewy Body Disease; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Organotechnetium Compounds; Parkinson Disease; Practice Patterns, Physicians'; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Tropanes

Early biomarkers for dementia with Lewy bodies (DLB) are lacking. To determine whether EEG differentiates the prodromal phase of DLB from other causes of mild cognitive impairment (MCI) and whether EEG is predictive for time to conversion from MCI to DLB, we compared EEGs and clinical follow-up of patients with MCI due to DLB with those of patients with MCI due to Alzheimer disease (MCI-AD).. We compared 37 patients with MCI who developed DLB during follow-up or had an abnormal. The visual EEG score was higher in MCI-DLB (score >2 in 60%) compared to MCI-AD (score >2 in 8%,. Profound EEG abnormalities are already present in the prodromal stage of DLB and have diagnostic and prognostic value.. This study provides Class III evidence that EEG abnormalities are more common in MCI-DLB than MCI-AD.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Cognitive Dysfunction; Diagnosis, Differential; Disease Progression; Early Diagnosis; Electroencephalography; Female; Follow-Up Studies; Fourier Analysis; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Middle Aged; Netherlands; Peptide Fragments; Prospective Studies; Radiopharmaceuticals; Symptom Assessment; tau Proteins; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

To test the hypothesis that core and suggestive features in possible dementia with Lewy bodies (DLB) would vary in their ability to predict an abnormal dopamine transporter scan and therefore a follow-up diagnosis of probable DLB. A further objective was to assess the evolution of core and suggestive features in patients with possible DLB over time depending on the (123)I-FP-CIT SPECT scan result.. A total of 187 patients with possible DLB (dementia plus one core or one suggestive feature) were randomized to have dopamine transporter imaging or to follow-up without scan. DLB features were compared at baseline and at 6-month follow-up according to imaging results and follow-up diagnosis.. For the whole cohort, the baseline frequency of parkinsonism was 30%, fluctuations 29%, visual hallucinations 24%, and REM sleep behavior disorder 17%. Clinician-rated presence of parkinsonism at baseline was significantly (p = 0.001) more frequent and Unified Parkinson's Disease Rating Scale (UPDRS) score at baseline was significantly higher (p = 0.02) in patients with abnormal imaging. There was a significant increase in UPDRS score in the abnormal scan group over time (p < 0.01). There was relatively little evolution of the rest of the DLB features regardless of the imaging result.. In patients with possible DLB, apart from UPDRS score, there was no difference in the evolution of DLB clinical features over 6 months between cases with normal and abnormal imaging. Only parkinsonism and dopamine transporter imaging helped to differentiate DLB from non-DLB dementia.

Topics: Aged; Brain; Disease Progression; Europe; Female; Follow-Up Studies; Hallucinations; Humans; Lewy Body Disease; Male; Mental Status Schedule; Parkinsonian Disorders; Radiopharmaceuticals; REM Sleep Behavior Disorder; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes

Dementia with Lewy bodies (DLB) is underrecognised in clinical settings.. To investigate whether performing a (123)I-ioflupane injection ((123)I-FP-CIT also called DaTSCAN™) single photon emission computed tomography (SPECT) scan in patients with possible DLB would lead to a more certain diagnosis (probable DLB or non-DLB dementia).. We randomised 187 patients with possible DLB 2:1 to have a scan or not (control group). The outcome measure was a change in diagnosis to probable DLB or non-DLB.. There were 56 controls and 114 scanned patients, of whom 43% had an abnormal scan. More patients in the imaging group had a change in diagnosis compared with controls at 8 and 24 weeks (61% (n = 70) v. 4% (n = 2) and 71% (n = 77) v. 16% (n = 9); both P<0.0001). Clinicians were more likely to change the diagnosis if the scan was abnormal (82%) than if it was normal (46%).. Imaging significantly contributed to a more certain diagnosis, proving to be a useful adjunct in the work-up of patients with possible DLB.

Topics: Aged; Brain; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Lewy Body Disease; Male; Nortropanes; Predictive Value of Tests; Tomography, Emission-Computed, Single-Photon

Dementia with Lewy bodies (DLB) needs to be distinguished from other types of dementia because of important differences in patient management and outcome. Current clinically based diagnostic criteria for DLB have limited accuracy. Severe nigrostriatal dopaminergic degeneration occurs in DLB, but not in Alzheimer's disease or most other dementia subtypes, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the sensitivity and specificity, in the ante-mortem differentiation of probable DLB from other causes of dementia, of single photon emission computed tomography (SPECT) brain imaging with the ligand (123)I-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT), which binds to the dopamine transporter (DAT) reuptake site. Diagnostic accuracy, positive and negative predictive values, and inter-reader agreement were the secondary endpoints and a subgroup of possible DLB patients was also included.. We did a phase III study in which we used a (123)I-FP-CIT SPECT scan to assess 326 patients with clinical diagnoses of probable (n=94) or possible (n=57) DLB or non-DLB dementia (n=147) established by a consensus panel (in 28 patients no diagnosis could be made). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The study had 90% power to detect the differences between our anticipated sensitivity (0.80) and specificity (0.85) targets and prespecified lower thresholds (sensitivity 0.65, specificity 0.73) using one-sided binomial tests with a significance level of alpha=0.025.. Abnormal scans had a mean sensitivity of 77.7% for detecting clinical probable DLB, with specificity of 90.4% for excluding non-DLB dementia, which was predominantly due to Alzheimer's disease. A mean value of 85.7% was achieved for overall diagnostic accuracy, 82.4% for positive predictive value, and 87.5% for negative predictive value. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's kappa=0.87). The procedure was well tolerated with few adverse events.. A revision of the International Consensus Criteria for DLB has recommended that low DAT uptake in the basal ganglia, as shown by SPECT or PET imaging, be a suggestive feature for diagnosis. Our findings confirm the high correlation between abnormal (low binding) DAT activity measured with (123)I-FP-CIT SPECT and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from Alzheimer's disease.

Topics: Aged; Aged, 80 and over; Basal Ganglia; Binding, Competitive; Brain; Brain Chemistry; Diagnosis, Differential; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Lewy Body Disease; Male; Middle Aged; Observer Variation; Predictive Value of Tests; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

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

The occurrence of parkinsonism in Alzheimer's disease (AD) is quite common, however the molecular and neurochemical changes underlying such extrapyramidal features in AD have been not fully understood. Post-mortem as well as in vivo imaging study have produced conflicting results as regards the existence of dopaminergic changes in AD. Aim of the present study was to investigate in vivo the nigro-striatal dopaminergic function in a group of AD patients with parkinsonism. Thirteen patients with AD and extrapyramidal features not related to past neuroleptic use (AD-P) underwent SPECT with 123I-FP-CIT, a ligand of dopamine transporter, and the data were compared with those obtained in 15 patients with Diffuse Lewy Body Dementia (DLBD), 20 patients with Parkinson's disease (PD), and 8 healthy elderly controls. The analysis of the data was performed by regions-of-interest approach and calculations of the striatal-to-non specific (occipital lobes) radioactivity ratios were made. The 123I-FP-CIT striatal uptake in patients with AD-P was similar to that obtained in the control population. Both the DLBD and PD groups showed significantly lower 123I-FP-CIT uptake in all striatal areas with respect to AD-P and control groups (p < 0.005). The lack of dopamine transporter changes in our series of AD-P patients can indicate that dopaminergic presynaptic function is preserved in this population and that different dopaminergic changes such as postsynaptic ones, or different neurotransmitter alterations might underlie the extrapyramidal features in AD.

Topics: Aged; Alzheimer Disease; Basal Ganglia Diseases; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Lewy Body Disease; Male; Membrane Glycoproteins; Membrane Transport Proteins; Neostriatum; Nerve Tissue Proteins; Parkinson Disease; Radiopharmaceuticals; Receptors, Presynaptic; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

Dementia with Lewy bodies (DLB) is characterized by a wide clinical and biological heterogeneity, with sex differences reported in both clinical and pathologically confirmed DLB cohorts. No research evidence is available on sex differences regarding molecular neurotransmission. This study aimed to assess whether sex can influence neurotransmitter systems in patients with probable DLB (pDLB).. We included 123 pDLB patients (male/female: 77/46) and 78 control subjects (male/female: 34/44) for comparison, who underwent. We found comparable. Sex-specific differences in

Topics: Female; Humans; Lewy Body Disease; Male; Sex Characteristics; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Dopamine Plasma Membrane Transport Proteins; Humans; Lewy Body Disease; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Tomography, Emission-Computed, Single-Photon

Progressive nigrostriatal pathway degeneration occurs in individuals with dementia with Lewy bodies (LB). Our objective was to investigate whether repeat 123[I]-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) single photon emission computed tomography (SPECT) can identify progressive dopaminergic loss in mild cognitive impairment (MCI) with Lewy bodies (MCI-LB).. Individuals with MCI-LB and MCI due to Alzheimer disease (MCI-AD) underwent comprehensive clinical assessment, 123[I]-FP-CIT SPECT at baseline and annual reviews, and baseline cardiac. We recruited 20 individuals with MCI-AD, 11 with possible MCI-LB, 25 with probable MCI-LB, and 29 age-matched controls. The mean time between baseline and the final image was 1.6 years (SD = 0.9, range 1.0-4.3). The annual estimated change in SBR was 0.23 for controls (95% CI -0.07 to 0.53), -0.09 (-0.55 to 0.36) for MCI-AD, -0.50 (-1.03 to 0.04) for possible MCI-LB, and -0.48 (-0.89 to -0.06) for probable MCI-LB. The median annual percentage change in SBR in MCI-LB was -5.6% (95% CI -8.2% to -2.9%) and 2.1% (-3.5% to 8.0%) for MCI-AD. The extrapolated time for a normal scan to become abnormal was 6 years. Controls and MCI-AD showed no significant change in dopaminergic binding over time. The mean test-retest variation in controls was 12% (SD 5.5%), which cautions against overinterpretation of small changes on repeat scanning.. Progressive dopaminergic loss in the striatum is detectable using 123[I]-FP-CIT SPECT in MCI-LB at a group level. In clinical practice, individual change in striatal 123[I]-FP-CIT uptake seems to be of limited diagnostic value because of high test-retest variation.. This study provides Class II evidence that longitudinal declines in striatal uptake measured using 123[I]-FP-CIT SPECT are associated with MCI due to Lewy body disease but not MCI due to Alzheimer disease.

Topics: Aged; Alzheimer Disease; Cognitive Dysfunction; Dopaminergic Imaging; Humans; Lewy Body Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

The specific binding ratio (SBR) is an objective indicator of N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-[123I] iodophenyl) nortropane ([

Topics: Atrophy; Biomarkers; Brain; Computer Simulation; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Humans; Image Interpretation, Computer-Assisted; Lewy Body Disease; Monte Carlo Method; Neurodegenerative Diseases; Parkinson Disease; Predictive Value of Tests; Radiopharmaceuticals; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon; Tropanes

In Lewy body diseases (LBD), various symptoms occur depending on the distribution of Lewy body in the brain, and the findings of brain perfusion and dopamine transporter single-photon emission computed tomography (DAT-SPECT) also change accordingly. We aimed to evaluate the correlation between brain perfusion SPECT and quantitative indices calculated from DAT-SPECT in patients with LBD.. We retrospectively enrolled 35 patients with LBD who underwent brain perfusion SPECT with N-isopropyl-p-[. In patients with LBD, decreased PCR index correlated with hypoperfusion in the brainstem (medulla oblongata and midbrain) (uncorrected p < 0.001, k > 100), while decreased CPR index correlated with hypoperfusion in the right temporoparietal cortex (family-wise error corrected p < 0.05), right precuneus (uncorrected p < 0.001, k > 100), and bilateral temporal cortex (uncorrected p < 0.001, k > 100). However, there was no significant correlation between decreased SBR index and brain perfusion. Additionally, the MMSE score was correlated with hypoperfusion in the left temporoparietal cortex (uncorrected p < 0.001).. This study suggests that regional changes in striatal

Topics: Brain; Dopamine; Dopamine Plasma Membrane Transport Proteins; Humans; Lewy Bodies; Lewy Body Disease; Perfusion; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

The AUC was high with all ML methods (0.92-0.96) for high or low uptake. The AUC was the highest for symmetry or asymmetry with the kNN method (AUC 0.75) and the comma-dot feature with the GBT method (AUC 0.94). Based on the test data set, the diagnostic accuracy for a diagnosis of PS/PD/DLB was 0.86 ± 0.04 (SE), 0.87 ± 0.04, and 0.93 ± 0.02 for Models 1, 2 and 3, respectively. The AUC was optimal for Model 3, and significantly differed between Models 3 and 1 (p = 0.027), and 3 and 2 (p = 0.029).. Image features such as high or low uptake, symmetry or asymmetry, and comma- or dot-like profiles can be determined using ML. The diagnostic accuracy of differentiating PS/PD/DLB was the highest for the multivariate model with three features and age compared with the conventional ROI-based method.

Topics: Alzheimer Disease; Diagnosis, Differential; Humans; Iodine Radioisotopes; Lewy Body Disease; Machine Learning; Nortropanes; Parkinson Disease; Tomography, Emission-Computed, Single-Photon

Reduced nigrostriatal uptake on N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-[

Topics: Alzheimer Disease; Brain; Diagnosis, Differential; Female; Humans; Iodine Radioisotopes; Lewy Body Disease; Magnetic Resonance Imaging; Male; Multimodal Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Software; Tomography, Emission-Computed, Single-Photon; Tropanes

To provide evidence that cardiac I-123-metaiodobenzylguanidine sympathetic innervation imaging (MIBG) scintigraphy differentiates probable mild cognitive impairment with Lewy bodies (MCI-LB) from mild cognitive impairment due to Alzheimer disease (MCI-AD), we scanned patients with MCI and obtained consensus clinical diagnoses of their MCI subtype. We also performed baseline FP-CIT scans to compare the accuracy of MIBG and FP-CIT.. We conducted a prospective cohort study into the accuracy of cardiac MIBG scintigraphy in the diagnosis of MCI-LB. Follow-up clinical assessment was used to diagnose MCI-AD (no core features of MCI-LB and normal FP-CIT), probable MCI-LB (2 or more core features, or 1 core feature with abnormal FP-CIT), or possible MCI-LB (1 core feature or abnormal FP-CIT). For the comparison between MIBG and FP-CIT, only core clinical features were used for diagnosis.. We recruited 95 people with mild cognitive impairment. Cardiac MIBG was abnormal in 22/37 probable and 2/15 possible MCI-LB cases and normal in 38/43 MCI-AD cases. The sensitivity in probable MCI-LB was 59% (95% confidence interval [CI], 42%-75%), specificity 88% (75%-96%), and accuracy 75% (64%-84%). The positive likelihood ratio was 5.1 and negative likelihood ratio 0.46. With symptom-only diagnoses, the accuracies were 79% for MIBG (95% CI, 68%-87%) and 76% for FP-CIT (95% CI, 65%-85%).. Cardiac MIBG appears useful in early disease, with an abnormal scan highly suggestive of MCI-LB. Validation in a multicenter setting is justified.. This study provides Class I evidence that cardiac MIBG distinguishes MCI-LB from MCI-AD.

Topics: 3-Iodobenzylguanidine; Aged; Aged, 80 and over; Alzheimer Disease; Cognitive Dysfunction; Diagnosis, Differential; Female; Follow-Up Studies; Heart; Humans; Lewy Body Disease; Male; Myocardial Perfusion Imaging; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

To study the influence of concomitant Alzheimer's disease (AD) pathology in dementia with Lewy bodies (DLB) on dopamine transporter (DAT) and serotonin transporter (SERT) availability, using. Based on their cerebrospinal fluid biomarker profile, fifty-two patients with probable DLB were divided in a group with (DLB/AD+, N = 15) and without concomitant AD-pathology (DLB/AD-, N = 37). We conducted atrophy-corrected region of interest (ROI) analyses comparing binding ratios (BRs) in the DAT-rich striatal and SERT-rich extrastriatal brain areas (amygdala, hippocampus, thalamus, midbrain and pons).. DLB/AD+ patients had significantly lower. DLB/AD+ patients may have lower SERT binding in limbic brain regions than DLB/AD- patients, possibly indicating faster neurodegeneration in mixed pathology.

Topics: Aged; Alzheimer Disease; Amygdala; Comorbidity; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Hippocampus; Humans; Lewy Body Disease; Male; Middle Aged; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

Our rationale was to conduct a retrospective study comparing 3

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Corpus Striatum; Female; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Middle Aged; Parkinson Disease; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

Assessment of nigrostriatal degeneration is a key element to discriminate between dementia with Lewy bodies (DLB) and Alzheimer disease (AD), and it is often evaluated using ioflupane (. A nigroputaminal bundle mask was delineated on 12 healthy volunteers (HV) and applied to MRI diffusion-weighted data of 18 subjects with DLB, 21 subjects with AD and another group of 12 HV. The correlation between nigroputaminal fractional anisotropy (FA) values and. DLB patients showed a higher nigroputaminal FA values compared with both AD and HV-controls groups (p = 0.001 for both comparisons), while no difference was observed between HV-controls and AD groups (p = 0.450); at ROC analysis, the area under the curve for the discriminating DLB and AD subjects was 0.820; FA values correlated with. In DLB, nigroputaminal degeneration could be reliably assessed on MRI diffusion scans using a mask of nigroputaminal bundle trajectory. Nigroputaminal FA in DLB patients correlated with

Topics: Aged; Diagnosis, Differential; Diffusion Tensor Imaging; Female; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Putamen; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). The study aims at performing a case-controlled region-of-interest (ROI)-based analysis of. We included 157 patients with early degenerative parkinsonism (mean age 72.6 years, 44% female, mean disease duration at scan 1.6 years), i.e. PD (n = 59), multiple system atrophy parkinsonian variant (MSA-P, n = 17), progressive supranuclear palsy (PSP, n = 28), corticobasal syndrome (CBS, n = 19), dementia with Lewy bodies (DLB, n = 34) as well as 58 similarly-aged control participants.. This study provides evidence of a major extrastriatal

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Female; Humans; Lewy Body Disease; Male; Middle Aged; Multiple System Atrophy; Neurodegenerative Diseases; Parkinson Disease; Parkinsonian Disorders; Serotonin Plasma Membrane Transport Proteins; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon; Tropanes

Variations in alertness and attention are common in Lewy body diseases (LBD) and among the core features of dementia with Lewy bodies (DLB). Dopamine transporter SPECT is an accurate biomarker of nigrostriatal degeneration (NSD) in LBD.. The present study investigated performance on a computerized alertness test as a potential measure of attention in patients with NSD compared to patients without NSD.. Thirty-six patients with cognitive impairment plus at least one core feature of DLB referred for [123I]FP-CIT SPECT imaging were prospectively recruited. Performance in a computerized test of intrinsic alertness was compared between patients with and those without NSD as assessed by [123I]FP-CIT SPECT.. Reaction times to auditory stimuli (adjusted for age, sex, and education) were significantly longer in patients with NSD compared to those with a normal [123I]FP-CIT SPECT scan (p < 0.05). Statistical analyses revealed no significant differences comparing reaction times to visual stimuli or dispersion of reaction times between groups. Exploratory analysis in a subgroup of patients with available [18F]FDG PET revealed that longer reaction times were associated with decreased glucose metabolism in the prefrontal cortex (statistical parametric mapping, adjusted for age and sex; p < 0.005, cluster extent > 50 voxels).. Computerized assessment of auditory reaction times is able to detect alertness deficits in patients with NSD and might help to measure alertness deficits in patients with LBD and NSD. Future studies in larger samples are needed to evaluate the diagnostic utility of computerized alertness assessment for the differential diagnosis of LBD.

Topics: Aged; Aged, 80 and over; Attention; Brain; Female; Fluorodeoxyglucose F18; Humans; Lewy Body Disease; Male; Middle Aged; Neostriatum; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Single Photon Emission Computed Tomography Computed Tomography; Substantia Nigra; Tropanes; Wakefulness

Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.. We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.. The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2-68.6], with a specificity of 89.0% (95% CI 70.8-97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5-77.4) and in possible MCI-LB was 40.0% (95% CI 16.4-67.7).. Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognitive Dysfunction; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Lewy Body Disease; Male; Neuroimaging; Sensitivity and Specificity; Tomography, Emission-Computed; Tropanes

To calculate the specific binding ratio (SBR) appropriately in dopamine transporter (DAT) imaging, a method for extracting the striatal volume of interest (VOI) was developed.. This study included 200 patients (72 ± 10 years) who were suspected of parkinsonian syndromes (PS) or dementia with Lewy body (DLB). The patients were divided into three groups of PS with dopaminergic degeneration, DLB and non-PS after [. The mean SBR values for the PS and DLB groups were significantly different from that of the non-PS group with both methods. The coefficients of variation of the SBR were significantly smaller with the proposed method compared with those of SBR. Our new method for SBR calculation in the FP-CIT SPECT showed less coefficients of variation with high reproducibility, which would be useful for clinical diagnosis and in assessing the severity of diseases in follow-up studies.

Topics: Aged; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Processing, Computer-Assisted; Lewy Body Disease; Male; Neostriatum; Observer Variation; Parkinsonian Disorders; Protein Binding; ROC Curve; Tomography, Emission-Computed, Single-Photon; Tropanes

We report a 77-year-old woman suffering from dementia with Lewy bodies (DLB) who presented with Hashimoto encephalopathy. The patient began to mistakenly believe that another person was sleeping in her bed from approximately 70 years of age. She began to show symptoms of parkinsonism after 75 years of age. One night, the patient began to exhibit loitering behavior, and made incomprehensible comments while also exhibiting other abnormal behaviors. Clinical examination revealed rigidity and tremor of the limbs, as well as hallucination, abnormal speech and behavior. We first considered DLB. However, serum anti-thyroglobulin levels turned out to be elevated, indicating Hashimoto encephalopathy as well, and treated the patient with steroid pulse therapy. Her mental symptoms subsequently improved, but rigidity and tremor remained.

Topics: Aged; Autoantibodies; Biomarkers; Encephalitis; Female; Hashimoto Disease; Humans; Immunotherapy; Iodine Radioisotopes; Lewy Body Disease; Methylprednisolone; Nortropanes; Phosphopyruvate Hydratase; Prednisolone; Pulse Therapy, Drug; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are thought to be part of a spectrum: both have a clinical profile including symptoms associated with dopaminergic and serotonergic loss, yet few imaging studies have focused on serotonergic neurodegeneration in both disorders. We aimed to study degeneration of terminals with dopamine and serotonin transporter (DAT and SERT, respectively) in patients with early-stage PD and DLB relative to healthy controls, using

Topics: Aged; Cross-Sectional Studies; Dopamine Plasma Membrane Transport Proteins; Female; Hippocampus; Humans; Hypothalamus; Lewy Body Disease; Male; Middle Aged; Neostriatum; Parkinson Disease; Retrospective Studies; Serotonin Plasma Membrane Transport Proteins; Thalamus; Tomography, Emission-Computed, Single-Photon; Tropanes

Lewy body disease is postulated, by the Braak model, to originate in the enteric nervous system, before spreading to the central nervous system. Therefore, a high prevalence of gastroparesis symptoms would be expected in prodromal dementia with Lewy bodies (DLB) and be highest in those with a dopaminergic deficit on imaging. The aim of this study was to explore whether gastroparesis symptoms are an early diagnostic marker of prodromal DLB and explore the relationship between symptoms and dopaminergic imaging findings on FP-CIT SPECT.. We recruited 75 patients over 60 with mild cognitive impairment (MCI), 48 with MCI with suspected Lewy body disease (MCI-LB) and 27 with MCI with suspected Alzheimer's disease (MCI-AD). All patients completed the Gastroparesis Cardinal Symptom Index (GSCI) questionnaire and also underwent FP-CIT [. At least one symptom suggestive of gastroparesis was reported in 48% (n = 23) MCI-LB vs 37% MCI-AD (n = 10) (P = 0.36). Rates of definite symptoms of gastroparesis, as defined by a GCSI total score ≥ 1.90, were rare and rates in MCI-LB were not different from MCI-AD (6% vs 0%, p = 0.55). After adjusting for gender differences between groups, no difference in gastroparesis symptom prevalence (2.27 vs 0.81 P = 0.05) or severity score (0.62 vs 0.28, p = 0.28) was noted between normally and abnormally visually rated FP-CIT SPECT scans.. The GCSI is not a useful tool for differentiating MCI-LB from MCI-AD. A low rate of definite gastroparesis was detected in prodromal DLB. No association was found between gastroparesis symptoms and FP-CIT SPECT findings.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Female; Gastroparesis; Humans; Lewy Body Disease; Male; Middle Aged; Prevalence; Prodromal Symptoms; Tomography, Emission-Computed, Single-Photon; Tropanes

Little is known regarding the clinical relevance or neurobiology of subtle motor disturbance in Alzheimer's disease (AD). This study aims to investigate the patterns of striatal. Patients with ADCI with mild parkinsonism exhibited decreased DAT availability in the caudate that was intermediate between healthy controls and patients with DLB. The DAT availability in other striatal subregions, including the posterior putamen, did not differ between the ADCI with parkinsonism and healthy control groups. The ROC analysis showed that DAT availability of all striatal subregions, especially the whole striatum, had a fair discriminatory power. Parkinsonian motor severity did not correlate with the striatal DAT availability in ADCI with parkinsonism.. The present study demonstrated that patients with ADCI with mild parkinsonism had distinct DAT scan patterns and suggests that parkinsonism is associated with the extranigral source of pathology.

Topics: Aged; Alzheimer Disease; Corpus Striatum; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Lewy Body Disease; Male; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity; Tropanes

Topics: Humans; Iodine Radioisotopes; Lewy Body Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).. Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.. MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD.. MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognitive Dysfunction; Female; Humans; Lewy Bodies; Lewy Body Disease; Male; Middle Aged; Tomography, Emission-Computed, Single-Photon; Tropanes

We aimed at examining sensitivity of combined visual and semi-quantitative. 3/155 (2.1%) subjects with degenerative parkinsonism (1 CBS, 1 MSA-C and 1 PD) and 1/53 (1.9%) with DLB had a normal visual SPECT. Subsequent semi-quantitative analysis showed mild striatal uptake impairment for the DLB and the PD subject. Therefore, only two patients (1 CBS and 1 MSA) had a strictly normal combined assessment.. The present study shows that SWEDD cases represent a negligible proportion of patients with degenerative conditions (1.3%), when stringent diagnostic criteria are applied, a thorough follow-up is performed and visual SPECT analysis is combined with precise semi-quantitative assessment.

Topics: Adult; Aged; Aged, 80 and over; Brain; Dopamine; Female; Humans; Lewy Body Disease; Male; Middle Aged; Multiple System Atrophy; Neurodegenerative Diseases; Parkinsonian Disorders; Prospective Studies; Retrospective Studies; Sensitivity and Specificity; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon; Tropanes; Young Adult

Topics: Dopamine; Humans; Lewy Body Disease; Neurodegenerative Diseases; Parkinson Disease; Presynaptic Terminals; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Brain; Humans; Lewy Body Disease; Parkinsonian Disorders; Tomography, Emission-Computed, Single-Photon; Tropanes

Dopaminergic loss on. We aimed to develop a new visual rating scale for. Four experienced observers developed and tested a new scale consisting of two metrics, reflecting overall loss and heterogeneity of loss. 66 subjects were used during development including clinical diagnoses of Alzheimer's disease (n = 14), Parkinson's disease (n = 9), Parkinson's disease dementia (n = 9), dementia with Lewy bodies (n = 15) and normal controls (n = 19). The scale was then tested on an independent group of 46 subjects with autopsy confirmed diagnosis: Alzheimer's disease (n = 11), Parkinson's disease (n = 3), Parkinson's disease dementia (n = 15), dementia with Lewy bodies (n = 12), normal controls (n = 4) and Frontotemporal dementia (n = 1).. In the autopsy validation the sensitivity and specificity of the new scale for Lewy body disease was 97% and 100% respectively, compared with the standard scale which had the same sensitivity (97%), but lower specificity (80%). The new scale had excellent inter rater reliability (intra-class correlation coefficient 0.93).. A new robust and reliable rating scale is described that straightforwardly captures the visual appearance of

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Female; Humans; Image Processing, Computer-Assisted; Lewy Body Disease; Male; Nortropanes; Parkinson Disease; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

The objective of this study was to investigate the discriminating value of a range of CSF α-synuclein species for dementia with Lewy bodies compared with Alzheimer's disease, PD, and cognitively normal controls.. We applied our recently published enzyme-linked immunosorbent assays to measure the CSF levels of total α-synuclein, oligomeric α-synuclein, and phosphorylated α-synuclein in dementia with Lewy bodies (n = 42), Alzheimer's disease (n = 39), PD (n = 46), and controls (n = 78). General linear models corrected for age and sex were performed to assess differences in α-synuclein levels between groups. We used backward-elimination logistic regression analysis to investigate the combined discriminating value of the different CSF α-synuclein species and Alzheimer's disease biomarkers.. CSF levels of total α-synuclein were lower in dementia with Lewy bodies and PD compared with Alzheimer's disease as well as controls (P < 0.001). In contrast, CSF levels of oligomeric α-synuclein were higher in dementia with Lewy bodies and PD compared with Alzheimer's disease (P < 0.05) and controls (P < 0.001). No group differences were found for phosphorylated α-synuclein. In dementia with Lewy bodies and PD, CSF total α-synuclein levels positively correlated with tau and phosphorylated tau (both r > 0.40, P < 0.01), but not with amyloid-β. CSF α-synuclein species could be useful as part of a biomarker panel for dementia with Lewy bodies. Evaluating both oligomeric α-synuclein and total α-synuclein in CSF helps in the diagnosis of dementia with Lewy bodies. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Topics: Aged; alpha-Synuclein; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Electroencephalography; Female; Humans; Lewy Body Disease; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Peptide Fragments; Psychiatric Status Rating Scales; Retrospective Studies; tau Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

It is widely known that there is low striatal. Patients with Alzheimer's disease (AD) (n = 95) and patients with DLB (n = 133) who underwent DAT-SPECT were enrolled. We examined the correlation between symptoms [cognitive function decline, fluctuations, visual hallucinations, parkinsonism, and REM sleep behavior disorder (RBD)] and regional striatal DAT uptake in the patients with DLB.. When comparing the DLB patients with or without fluctuations, visual hallucinations, or RBD, there were no significant differences in DAT uptake in any regions of the striatum. DLB patients with parkinsonism had significantly lower DAT uptake in entire striatum, entire putamen, and anterior putamen compared to DLB patients without parkinsonism. Moreover, there was weak but significant correlation between severity of parkinsonism and DAT uptake in entire regions of the striatum in patients with DLB. There was no significant correlation between cognitive function and DAT uptake in any regions of the striatum in patients with DLB.. In patients with DLB, only parkinsonism is associated with a reduction in striatal DAT uptake.

Topics: Aged, 80 and over; Biological Transport; Cognition; Female; Humans; Lewy Body Disease; Male; Neostriatum; Tomography, Emission-Computed, Single-Photon; Tropanes

Visual and semi-quantitative assessments of

Topics: Aged; Aged, 80 and over; Brain; Corpus Striatum; Diagnosis, Differential; Female; Humans; Lewy Body Disease; Male; Neurodegenerative Diseases; Retrospective Studies; Sensitivity and Specificity; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Autopsy; Humans; Iodine Radioisotopes; Lewy Body Disease; Neuroimaging; Tropanes

Topics: Autopsy; Humans; Iodine Radioisotopes; Lewy Body Disease; Neuroimaging; Tropanes

Dopamine transporter single photon emission CT (DAT-SPECT) is useful in the evaluation of dementia with Lewy bodies (DLB). The specific binding ratio (SBR) is an index to measure DAT density. However, poorly reproducible cases are occasionally experienced in clinical practice. We hypothesized that distance-weighted histogram (DWH) may be useful to improve the reproducibility of SBR. The purpose of this study was to investigate inter- and intra-observer reproducibility of SBR with conventional and DWH methods, and to visually evaluate the precision in reference voxel of interest (VOI) definition using these methods.. This study included 50 adult patients with probable DLB. They underwent brain MRI, DAT-SPECT, and cerebral blood flow SPECT with N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP). SBR of the striatum was calculated using conventional and DWH method. For inter-observer reproducibility validation, conventional and DWH SBR were independently evaluated by experienced nuclear medicine physicians; these measurements were repeated by the nuclear medicine physician to investigate intra-observer reproducibility.. Proper reference VOI definition was achieved in 60.0% using conventional SBR and in 98.0% with DWH SBR. Both conventional and DWH SBR demonstrated good inter- and intra-observer reproducibility, however, there were statistically significant inter- and intra-observer variations with conventional SBR measurements. Average inter- and intra-observer errors of conventional SBR were 7.9 and 6.1%, respectively. Conversely, DWH SBR errors were not observed in all patients. Moreover, average inter- and intra-observer errors were significantly higher in conventional SBR with improper reference VOI definition than in that with proper reference VOI definition.. Although the reproducibility of conventional and DWH SBR was good, inter- and intra-observer bias could not be ignored in conventional SBR, particularly with improper reference VOI definition. Thus, DWH may be useful to improve inter- and intra-observer reproducibility of SBR.

Topics: Aged; Aged, 80 and over; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Processing, Computer-Assisted; Lewy Body Disease; Male; Middle Aged; Observer Variation; Tomography, Emission-Computed, Single-Photon; Tropanes

The aim of this study was to investigate the diagnostic value of occipital lobe and posterior cingulate perfusion in predicting dopamine transporter imaging outcome using a quantitative measure of analysis.. In total, 99 patients with cognitive complaints who had undergone both technetium-99m-hexamethylpropyleneamine oxime single-photon emission computed tomography (Tc-HMPAO SPECT) and I ioflupane (I-FP-CIT also called DaTSCAN) imaging in a dementia diagnostic center were analyzed. Measures of perfusion were calculated from HMPAO SPECT images for the medial and lateral occipital lobe, the posterior cingulate cortex, precuneus and cuneus regions of interest using statistical parametric mapping 8. DaTSCAN images were quantified and specific binding ratios were calculated independent from HMPAO SPECT results. Statistical parametric mapping and tests of associations between perfusion and I-FP-CIT imaging were completed.. Regions of interest on HMPAO yielded poor predictive values when used independently to predict I-FP-CIT status; however, the combination of normal posterior cingulate perfusion with medial and lateral occipital hypoperfusion was associated significantly with I-FP-CIT status, χ (1, N=99)=9.72, P=0.002. This combination also yielded a high positive likelihood ratio and specificity (11.1, 98%). Sensitivity was, however, low (22%). No significant perfusion differences were found when abnormal and normal I-FP-CIT groups were compared directly using voxel-based morphometry (P<0.05, family-wise error).. The combination of medial and lateral occipital hypoperfusion with preserved posterior cingulate gyrus perfusion is highly specific for individuals with a positive I-FP-CIT scan in a clinical sample where diagnostic doubt exists. This regional combination, however, lacks sensitivity; therefore, absence of the sign cannot be used to rule out dementia with Lewy bodies. A positive finding provides strong evidence to rule in dementia with Lewy bodies.

Topics: Aged; Cerebrovascular Circulation; Female; Gyrus Cinguli; Humans; Lewy Body Disease; Male; Occipital Lobe; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Tropanes

Evidence for the prodromal stage of dementia with Lewy bodies (DLB) is very limited. To address this issue, we investigate the. We enrolled subjects into a prodromal DLB group (PRD-DLB) (n = 20) and clinical DLB group (CLIN-DLB) (n = 18) and compared these groups with an Alzheimer's disease control group (AD) (n = 10). PRD-DLB was defined as patients having the non-motor symptoms associated with Lewy body disease (LBD) [i.e. REM sleep behavior disorder (RBD), olfactory dysfunction, autonomic dysfunction, and depression] and showing characteristic diffuse occipital hypometabolism in. Mean SBR scores of both PRD-DLB and CLIN-DLB were significantly lower than those of AD. No correlation was found between SBR and MMSE scores. Both in the CLIN-DLB and total DLB groups, SBR scores were negatively correlated with UPDRS3 scores, whereas no correlation was found in PRD-DLB. Among the LBD-related non-motor symptoms, duration of olfactory dysfunction, and RBD demonstrated negative correlation with SBR scores in PRD-DLB.

Topics: Aged; Cognition; Female; Humans; Lewy Body Disease; Male; Movement; Radiopharmaceuticals; Sleep; Tomography, Emission-Computed, Single-Photon; Tropanes

To conduct a validation study of. Patients >60 years of age with dementia who had undergone. Fifty-five patients (33 with DLB and 22 with Alzheimer disease) were included. Against autopsy diagnosis,. This large autopsy analysis of. This study provides Class I evidence that

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Autopsy; Chi-Square Distribution; Female; Humans; Lewy Body Disease; Male; Middle Aged; Neurologic Examination; Psychiatric Status Rating Scales; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon; Tropanes

To assess the validity of a semi-quantitative I-FP-CIT SPECT method, compared to the commonly used visual analysis, in patients with probable dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). We also studied DLB specific uptake impairment pattern and correlation of uptake in the presence or absence of parkinsonism.. Among 1202 scans performed at our center from 2003 to 2015, we identified 93 subjects with probable DLB (mean age 76.9 ± 6.8 years, 37% women) and 18 with AD (mean age 76.9 ± 8.1 years, 50% women). Independent visual and semi-quantitative assessments based on previously established on-site reference values (including volumes-of-interest uptake, caudate-to-putamen ratio and striatal asymmetry index) were performed and compared between both groups.. Visual staging was considered abnormal in 96.8% of DLB patients, whereas 97.8% of subjects had an abnormal semi-quantitative assessment. Combining both methods yielded a 100% sensitivity. Patients with DLB exhibited a more pronounced impairment of putaminal uptake when associated with parkinsonism, whereas a more diffuse pattern and significantly higher uptake values were observed in the subgroup of DLB patients without parkinsonism (resp. striatal uptake 1.61 ± 0.66 vs. 2.28 ± 0.52, P = 0.01). A minority of AD subjects show minimal alterations of presynaptic dopaminergic transport (striatal uptake 3.07 ± 0.41), values being always significantly higher than those from DLB patients, irrespective of the presence of parkinsonism (P < 0.0001) or not (P = 0.002).. Additional use of semi-quantitative analysis allows a higher discrimination of DLB from AD and demonstrates a specific pattern of degeneration in DLB patients according to their motor phenotype.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Diagnosis, Differential; Female; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Middle Aged; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: alpha-Synuclein; Female; Humans; Lewy Body Disease; Locus Coeruleus; Middle Aged; Mutation; Parkinson Disease; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

Little is known about the underlying mechanisms of clinical symptoms in dementia with Lewy bodies. The aim of this study was to explore the association between loss of striatal dopamine transporter binding and symptoms in dementia with Lewy bodies.. Thirty-five patients with dementia with Lewy bodies underwent single-photon emission computerized tomography brain imaging with N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([(123) I]FP-CIT). Associations between striatal binding ratios and motor (UPDRS), psychiatric (Neuropsychiatric Inventory; [NPI]), and cognitive (Mini-Mental State Examination [MMSE] and neuropsychological tests) symptoms were assessed by linear regression analysis.. The explorative analysis showed that the motor UPDRS was negatively associated with putamen dopamine transporter binding, whereas no association with striatal dopamine transporter binding was found for total NPI, hallucinations, apathy, depression, anxiety, and MMSE scores. However, in post-hoc analysis, executive impairment was positively associated with dopamine transporter loss after adjustment of age and gender.. Dopamine deficiency in patients with dementia with Lewy bodies was associated with severity of motor symptoms, but did not correlate significantly with ratings of neurobehavioral disturbances or overall cognition.

Topics: Aged; Aged, 80 and over; Cognition Disorders; Dopamine Plasma Membrane Transport Proteins; Female; Fluorine Radioisotopes; Humans; Lewy Body Disease; Linear Models; Male; Mental Disorders; Mental Status Schedule; Motor Activity; Protein Binding; Tomography, Emission-Computed, Single-Photon; Tropanes

Decreased striatal dopamine transporter (DAT) binding on SPECT imaging is a strong biomarker for the diagnosis of dementia with Lewy bodies (DLB). There is still a lot of uncertainty about patients meeting the clinical criteria for probable DLB who have a normal DAT SPECT scan (DLB/S-). The aim of this study was to describe the clinical and imaging follow-up in these patients, and compare them to DLB patients with abnormal baseline scans (DLB/S+).. DLB patients who underwent DAT imaging ([(123)I]FP-CIT SPECT) were selected from the Amsterdam Dementia Cohort. All [(123)I]FP-CIT SPECT scans were evaluated independently by two nuclear medicine physicians and in patients with normal scans follow-up imaging was obtained. We matched DLB/S-- patients for age and disease duration to DLB/S+ patients and compared their clinical characteristics.. Of 67 [(123)I]FP-CIT SPECT scans, 7 (10.4 %) were rated as normal. In five DLB/S- patients, a second [(123)I]FP-CIT SPECT was performed (after on average 1.5 years) and these scans were all abnormal. No significant differences in clinical characteristics were found at baseline. DLB/S- patients could be expected to have a better MMSE score after 1 year.. This study was the first to investigate DLB patients with the initial [(123)I]FP-CIT SPECT scan rated as normal and subsequent scans during disease progression rated as abnormal. We hypothesize that DLB/S- scans could represent a relatively rare DLB subtype with possibly a different severity or spread of alpha-synuclein pathology ("neocortical predominant subtype"). In clinical practice, if an alternative diagnosis is not imminent in a DLB/S- patient, repeating [(123)I]FP-CIT SPECT should be considered.

Topics: Aged; Aged, 80 and over; Female; Follow-Up Studies; Humans; Lewy Body Disease; Male; Middle Aged; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

To compare the diagnostic value of striatal (123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123) I-FP-CIT) single photon emission computed tomography (SPECT) and (123) I-metaiodobenzylguanidine ((123) I-MIBG) myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from other dementia types.. This prospective longitudinal study included 30 patients with a clinical diagnosis of DLB and 29 patients with non-DLB dementia (Alzheimer disease, n = 16; behavioral variant frontotemporal dementia, n = 13). All patients underwent (123) I-FP-CIT SPECT and (123) I-MIBG myocardial scintigraphy within a few weeks of clinical diagnosis. All diagnoses at each center were agreed upon by the local clinician and an independent expert, both unaware of imaging data, and re-evaluated after 12 months. Each image was visually classified as either normal or abnormal by 3 independent nuclear physicians blinded to patients' clinical data.. Overall, sensitivity and specificity to DLB were respectively 93% and 100% for (123) I-MIBG myocardial scintigraphy, and 90% and 76% for (123) I-FP-CIT SPECT. Lower specificity of striatal compared to myocardial imaging was due to decreased (123) I-FP-CIT uptake in 7 non-DLB subjects (3 with concomitant parkinsonism) who had normal (123) I-MIBG myocardial uptake. Notably, in our non-DLB group, myocardial imaging gave no false-positive readings even in those subjects (n = 7) with concurrent medical illnesses (diabetes and/or heart disease) supposed to potentially interfere with (123) I-MIBG uptake.. (123) I-FP-CIT SPECT and (123) I-MIBG myocardial scintigraphy have similar sensitivity for detecting DLB, but the latter appears to be more specific for excluding non-DLB dementias, especially when parkinsonism is the only "core feature" exhibited by the patient. Our data also indicate that the potential confounding effects of diabetes and heart disease on (123) I-MIBG myocardial scintigraphy results might have been overestimated. Ann Neurol 2016;80:368-378.

Topics: 3-Iodobenzylguanidine; Aged; Aged, 80 and over; Alzheimer Disease; Corpus Striatum; Diagnosis, Differential; Female; Frontotemporal Dementia; Humans; Lewy Body Disease; Male; Middle Aged; Myocardial Perfusion Imaging; Prospective Studies; Radiopharmaceuticals; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

I-FP-CIT SPECT is increasingly used to differentiate between Alzheimer's dementia (AD) and dementia with Lewy bodies (DLB). The role of I-FP-CIT SPECT in frontotemporal dementia (FTD) is rather unclear, albeit nigrostriatal involvement may occur. The aim of this study was to evaluate its role in the differentiation of FTD, DLB, and AD.. We analyzed 34 patients with clinical diagnosis of FTD (n = 13), DLB (n = 12), and AD (n = 9) undergoing combined F-FDG PET and I-FP-CIT SPECT. We performed a semiquantitative region of interest-based analysis to determine the binding potential values in caudate nucleus, putamen, and whole striatum including the caudate/putamen binding potential ratio and asymmetry indices. The receiver operating characteristic analyses and multinomial logistic regression were conducted to assess discrimination accuracy.. The putaminal binding potential separated DLB from AD with high accuracy (area under the receiver operating characteristic curve [AUC], 0.94). It also discriminated FTD from DLB with high accuracy (AUC, 0.92), whereas differentiation between FTD and AD was less accurate (AUC, 0.74). The binding potential ratio also provided high accuracy for differentiation of FTD and DLB (AUC, 0.91). Combination of these 2 parameters yielded slightly higher results for differentiation of FTD and DLB (AUC, 0.97). In a group including all patients, accuracy remained very high for DLB (AUC, 0.95), whereas values for FTD (AUC, 0.81) and AD (AUC, 0.80) were lower.. Semiquantitative assessment of striatal dopamine transporter availability can differentiate between FTD and DLB as well as DLB and AD with high accuracy, whereas discrimination between AD and FTD is limited.

Topics: Aged; Alzheimer Disease; Diagnosis, Differential; Female; Frontotemporal Dementia; Humans; Lewy Body Disease; Male; Middle Aged; Organ Specificity; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

Although parkinsonism is considered a core feature of dementia with Lewy bodies (DLB), it is occasionally mild or even absent. I-FP-CIT SPECT has been accepted as a diagnostic support tool in this context, given that low striatal uptake is associated with neuronal loss. The aim of this retrospective study was to look for correlations between I-FP-CIT uptake in the striatum and clinical extrapyramidal signs (EPSs) in patients with a diagnosis of probable DLB to clarify the extent to which the supporting role of I-FP-CIT is related to motor impairment.. Semiquantitative I-FP-CIT uptake was analyzed and correlated with Unified Parkinson Disease Rating Scale Part III scores in a sample of 22 patients with a diagnosis of probable DLB and a wide range of EPSs.. A significant negative linear correlation between I-FP-CIT uptake and Unified Parkinson Disease Rating Scale Part III score was found both in the caudate and the putamen (r = -0.69 and -0.72, respectively, P < 0.001). Striatal uptake in patients with no or questionable EPS was comparable to that recorded in normal age-matched subjects (99% [22%] in the putamen) but significantly reduced in those with mild and severe EPS (43% [35%] and 30% [17%], respectively, P < 0.0001, but P = nonsignificant between mild and severe EPS).. SPECT may be redundant when there are no doubts about the parkinsonism (ie, when it is absent or unequivocally present), but it may be helpful in identifying presynaptic nigrostriatal degeneration in patients with mild EPSs.

Topics: Aged; Female; Humans; Lewy Body Disease; Male; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

We present a case demonstrating how correlative imaging with (123)I-ioflupane SPECT and (18)F-FDG PET can be used to help make the diagnosis of Lewy body disease more specific.

Topics: Aged, 80 and over; Brain; Diagnosis, Differential; Fluorodeoxyglucose F18; Humans; Lewy Body Disease; Male; Nortropanes; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

In elderly patients, exposure to antipsychotic medication and subsequent withdrawal may lead to the development of persistent extrapyramidal symptoms, possibly including a syndrome suggested to be tardive parkinsonism. We describe a case in which withdrawal of antipsychotics was unexpectedly associated with progressive deterioration, rather than improvement, of extrapyramidal parkinsonian symptoms. Abnormal imaging of presynaptic dopamine transporters (DaTs) using single-photon emission computed tomography (SPECT) with ioflupane I 123 (DaTscan) substantially contributed to the differential diagnosis, suggesting it was likely that the patient had an underlying neurodegenerative disorder that preceded the onset of medicationinduced parkinsonian symptoms. Our report illustrates how novel findings from DaTscan may assist with diagnosing the cause of persistent parkinsonian symptoms after antipsychotic withdrawal and provide insight into the controversial concept of tardive parkinsonism.

Topics: Aged, 80 and over; Antipsychotic Agents; Brain; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Haloperidol; Humans; Iodine Radioisotopes; Lewy Body Disease; Neuroimaging; Nortropanes; Parkinson Disease, Secondary; Tomography, Emission-Computed, Single-Photon

In this study, (123)I-FP-CIT biodistribution and dosimetry was determined in 10 adult male patients using planar gamma camera imaging alone or in combination with single photon emission computed tomography /X-ray computed tomography (SPECT/CT) imaging. Dosimetric assessment using planar plus SPECT/CT imaging resulted in significantly different estimates of organ-absorbed doses compared to estimates based on planar imaging alone. We conclude that the use of complementary SPECT/CT measurements in biodistribution studies is valuable for determining the organ doses more accurately.

Topics: Aged; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Middle Aged; Parkinsonian Disorders; Radiometry; Radiopharmaceuticals; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Tropanes

Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common neurodegenerative dementia types. It is important to differentiate between them because of the differences in prognosis and treatment approaches.. Investigate if sparse partial least squares (SPLS) classification of cortical thickness measurements could differentiate between AD and DLB.. Two independent cohorts without MR-protocol alignment in Norway and Slovenia with 97 AD and DLB subjects were enrolled. Cortical thickness measurements acquired with Freesurfer were used in subsequent SPLS classification runs. The cohorts were analyzed separately and afterwards combined. The models were trained with leave-one-out cross validation and test datasets where used when available. To study the impact of MR-protocol alignment, the classifiers were additionally tested on sets drawn exclusively from the independent cohorts.. The obtained sensitivity/specificity/AUC values were 94.4/88.89/0.978 and 88.2/94.1/0.969 in the Norwegian and Slovenian cohorts, respectively. Both cohorts showed AD-associated pattern of thinning in mid-anterior temporal, occipital and subgenual cingulate cortex, whereas the pattern supportive for DLB included thinning in dorsal cingulate, posterior temporal and lateral orbitofrontal regions. When combining the cohorts, sensitivity/specificity/AUC were 82.1/85.7/0.948 for the training and 77.8/75/0.731 for the testing datasets with the same pattern-of-difference. The models tested on datasets drawn exclusively from the independent cohorts did not produce adequate accuracy.. SPLS classification of cortical thickness is a good method for differentiating between AD and DLB, relatively stable even for mixed data, but not when tested on completely independent data drawn from different cohorts (without MR-protocol alignment).

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Area Under Curve; Brain Mapping; Cerebral Cortex; Cohort Studies; Female; Humans; Imaging, Three-Dimensional; Lewy Body Disease; Magnetic Resonance Imaging; Male; Multivariate Analysis; Postmortem Changes; Principal Component Analysis; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Alzheimer Disease; Female; Frontotemporal Dementia; Humans; Lewy Body Disease; Male; Tomography, Emission-Computed, Single-Photon; Tropanes

There is increasing evidence that imaging with [123I]FP-CIT SPECT is helpful in differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) but it is not known how well the scan performs in differentiating DLB from frontotemporal dementia (FTD).. We compared the striatal dopamine transporter (DAT) binding in FTD (n=12), DLB (n=10) and AD (n=9) by visually rating the caudate and putamen on [123I]FP-CIT SPECT scans.. The majority (9/10) of DLB cases had an abnormal scan and a significant reduction of uptake of DAT binding in the putamen and the caudate. A third (4/12) of the FTD cases also had an abnormal scan and a significant reduction in uptake in the putamen and the caudate. In contrast, only one out of nine AD cases had an abnormal scan. Significant differences were found when comparisons were made between the groups for visual analysis of the entire scan (p=0.001) and the four regions of interest (p=0.001 - 0.013). In contrast to the AD group (specificity of scan 89%), the specificity of [123I]FP-CIT SPECT scans was reduced in the FTD group to 67%. Three quarters of the study population had at least one extrapyramidal motor sign (EPMS), with bradykinesia being the most common EPMS in both FTD (83%) and DLB (70%).. This study highlights to clinicians that a positive (abnormal) [123I]FP-CIT SPECT scan, even in a patient with an EPMS, does not exclude the diagnosis of FTD and emphasises the importance of a comprehensive clinical evaluation and a detailed cognitive assessment.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Caudate Nucleus; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Frontotemporal Dementia; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Putamen; Tomography, Emission-Computed, Single-Photon; Tropanes

Dementia with Lewy Bodies (DLB) must be distinguished from other types of dementia because of important differences in patient management and outcome. Both reduction in cardiac 123I-metaiodobenzilguanidine (MIBG) uptake and decreased 123I-FP-CIT binding in basal ganglia have been described in DLB. The aim of this study was to assess the relationship between cardiac sympathetic activity and nigrostriatal degeneration in patients with probable DLB.. Twenty-eight patients (15 males; mean age 77 years, range 64-88 years) with clinical international criteria of probable DLB were included in the study. All patients underwent a cardiac MIBG scintigraphy and a FP-CIT SPECT. Global cardiac MIBG uptake was semiquantified by means of heart-to-mediastinum ratio (HMR) (normal >1.56). FP-CIT binding in basal ganglia was calculated and compared with an age-matched control group. The relation between cardiac MIBG uptake and FP-CIT uptake in basal ganglia, and the relationship of these two techniques with distinctive symptoms of DLB, features of past medical history and data from the neuropsychological examination were assessed.. Cardiac MIBG uptake was decreased in 23 of 28 patients (HMR=1.32, range 0.95-1.85). The FP-CIT binding in basal ganglia was significantly lower than in control group (2.01±0.5 vs 2.62±0.2, P<0.05). All patients with reduced cardiac HMR showed decreased FP-CIT binding in basal ganglia. There was a positive correlation between the HMR and specific binding ratio of striatum (P<0.01). A high correlation between FP-CIT SPECT and the presence of parkinsonism also was found. No correlation between cardiac MIBG uptake and demographic, clinical or neuropsychological data was found.. In probable DLB cardiac MIBG uptake and FP-CIT binding in basal ganglia are reduced. The positive correlation between both measures suggests that cardiac sympathetic degeneration and nigrostriatal degeneration parallel similarly in patients with probable DLB.

Topics: 3-Iodobenzylguanidine; Aged; Aged, 80 and over; Basal Ganglia; Female; Heart Diseases; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Retrospective Studies; Striatonigral Degeneration; Sympathetic Nervous System; Tomography, Emission-Computed, Single-Photon; Tropanes

To assess the impact of imaging the presynaptic dopaminergic terminal using DaTSCAN single-photon emission computed tomography (SPECT) on the clinical diagnosis and subsequent management of patients with possible dementia with Lewy bodies (DLB), who were referred for imaging.. A retrospective case note study was undertaken, involving a series of consecutive patients who had undergone DaTSCAN SPECT 12-24 months earlier.. Case notes of 80 patients were reviewed. DaTSCAN imaging results were abnormal (indicating DLB) in 20 (25%) and normal (suggesting an alternative diagnosis or absence of disease) in 60 (75%) patients. Of the 20 patients with an abnormal scan, 18 had a postscan working clinical diagnosis of DLB (90%), one had diagnosis of vascular dementia (5%) and another had no recorded outcome (5%). Fifty-eight out of the 60 patients with a normal DaTSCAN image result had an alternative clinical diagnosis of DLB (95%). Consequently, DaTSCAN findings were concordant with the outcome clinical diagnosis in 76 out of the 80 (95%) cases. Subsequent to DaTSCAN SPECT, scan findings and diagnoses were discussed with patients and/or their carers in 94% of cases and subsequent treatment options discussed in 93% of cases.. It would seem that DaTSCAN imaging has a marked influence on the working clinical diagnosis and subsequent management of patients with suspected DLB.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Corpus Striatum; Diagnosis, Differential; Female; Humans; Lewy Body Disease; Male; Observer Variation; Predictive Value of Tests; Presynaptic Terminals; Radiography; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

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

To explore the presenting and early symptoms of dementia with Lewy bodies (DLB).. Patients with mild dementia fulfilling diagnostic criteria for DLB (n = 61) and Alzheimer's disease (AD) (n = 109) were recruited from outpatient dementia clinics in western Norway. At diagnosis, caregivers were asked which symptom had been the presenting symptom of dementia.. Caregivers reported that memory impairment was the most common presenting symptom in DLB (57%), followed by visual hallucinations (44%), depression (34%), problem solving difficulties (33%), gait problems (28%), and tremor/stiffness (25%). In contrast, 99% of AD carers reported impaired memory as a presenting symptom, whereas visual hallucinations were a presenting symptom in 3% of the AD cases.. DLB should be suspected in predementia cases with visual hallucinations.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Caregivers; Cognition; Delirium; Depression; Diagnostic and Statistical Manual of Mental Disorders; Dopamine Plasma Membrane Transport Proteins; Educational Status; Female; Gait Disorders, Neurologic; Hallucinations; Humans; Lewy Body Disease; Male; Middle Aged; Neuropsychological Tests; Norway; Radiopharmaceuticals; Retrospective Studies; Surveys and Questionnaires; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes

Topics: Aged, 80 and over; Female; Humans; Iodine Radioisotopes; Lewy Body Disease; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon; Tropanes

(123)I-FP-CIT SPECT (single photon emission computed tomography) can help in the differential diagnosis of probable dementia with Lewy bodies (Lewy body dementia) and Alzheimer's disease.. Our aim was to determine the accuracy of (123)I-FP-CIT SPECT in diagnosing people with possible dementia with Lewy bodies.. We undertook a 12-month follow-up of 325 individuals with probable or possible Lewy body or non-Lewy body dementia who had previously undergone (123)I-FP-CIT SPECT. A consensus panel, masked to SPECT findings, established diagnosis at 12 months in 264 people.. Of 44 people with possible dementia with Lewy bodies at baseline, at follow-up the diagnosis for 19 people was probable dementia with Lewy bodies (43%), in 7 people non-Lewy body dementia (16%) and for 18 individuals it remained possible dementia with Lewy bodies (41%). Of the 19 who at follow-up were diagnosed with probable dementia with Lewy bodies, 12 had abnormal scans at baseline (sensitivity 63%); all 7 individuals with a possible diagnosis who were diagnosed as having Alzheimer's disease at follow-up had normal scans (specificity 100%).. Our findings confirm the diagnostic accuracy of (123)I-FP-CIT SPECT in distinguishing Lewy body from non-Lewy body dementia and also suggest a clinically useful role in diagnostically uncertain cases, as an abnormal scan in a person with possible dementia with Lewy bodies is strongly suggestive of dementia with Lewy bodies.

Topics: Aged; Aged, 80 and over; Female; Follow-Up Studies; Humans; Lewy Bodies; Lewy Body Disease; Male; Middle Aged; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

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

Neuropsychiatric symptoms are frequent in dementia with Lewy bodies (DLB). Dopamine transporter (DAT) imaging with (123)I-labeled ligand N-delta-(fluoropropyl)-2 beta-carbomethoxy-3beta-(4-iodophenyl)tropene ((123)I-FP-CIT), which reliably measures midbrain dopaminergic dysfunction, has provided important evidence on the neurobiological substrate of some of these symptoms including apathy and depression. However, little is known on DAT levels and other distressing symptoms such as delusions and hallucinations. Therefore, (123)I-FP-CIT imaging was performed in 18 well-characterized patients with DLB, and striatal DAT levels were correlated with the frequency/severity ratings of several neuropsychiatric symptoms. A wide range of neuropsychiatric symptoms could be observed in the sample. Significant correlations were observed between decreased striatal DAT levels and visual hallucinations. Although there were no correlations between striatal DAT levels and other neuropsychiatric symptoms, when considering the putamen and the caudate nucleus separately, delusions, depression, and apathy were inversely correlated to decreased caudate DAT levels. The seresults provide intriguing evidence on the involvement of the mesocortical dopaminergic pathways in neuropsychiatric symptoms in DLB.

Topics: Aged; Caudate Nucleus; Delusions; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Hallucinations; Humans; Image Processing, Computer-Assisted; Lewy Body Disease; Male; Middle Aged; Neostriatum; Neuropsychological Tests; Nucleus Accumbens; Parkinson Disease; Psychiatric Status Rating Scales; Putamen; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

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

There is a strong association between the e4 allele of apolipoprotein E (APOE) and Alzheimer's disease (AD). This converts this allele into a risk factor for the development of AD. The association between APOE4 and dementia with Lewy bodies (DLB) is under discussion. In DLB, the presence of APOE4 has been related with a greater amount of senile plaques and neurofibrillary tangles.. This is a case-control study in which the APOE genotype was determined using the modified PCR technique of Wenham in 306 patients with diagnosis of probably AD, NINCDS-ADRDA criteria, 58 cases of probably DLB, McKeith et al. consensus criteria (1996), all of them with SPECT with pathological 123I-FP-CIT and 80 normal controls (NC) having similar age and gender distribution.. The frequency of alleles was: DLB group epsilon4: 16%; epsilon3: 75%; epsilon2: 9%; AD: epsilon4: 32%; epsilon3: 67%; epsilon2: 1%; and in the normal control group: epsilon4: 12%; epsilon3: 83%; epsilon2: 5%. The percentage of alleles in both genders was similar in the three groups.. APOE4 percentage in DLB group (16%) was lower than in AD group (32%), and similar to the control group (12%). Considering that the presence of morphopathological Alzheimer type alterations in DBL, essentially neurofibrillary tangles, is inversely correlated with the presence of Parkinsonian signs, this group may represent pure forms of the disease, although the lack of neuropathological demonstration does not make it possible to confirm this hypothesis.

Topics: Alzheimer Disease; Apolipoprotein E4; Carbon Radioisotopes; Female; Gene Frequency; Genotype; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Tomography, Emission-Computed, Single-Photon; Tropanes

123I-labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) imaging is a diagnostic tool to help differentiate dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). However, in animals, cholinesterase inhibitors (ChEi) have been reported to reduce radioligand binding to the striatal dopamine transporter. As ChEi are frequently used in people with dementia, it is important to determine whether their use affects 123I-FP-CIT uptake in the striatum.. To clarify whether chronic ChEi therapy modulates striatal dopamine transporter binding measured by 123I-FP-CIT in patients with AD, DLB and Parkinson's disease with dementia (PDD).. Cross sectional study in 99 patients with AD (nine on ChEi, 25 not on ChEi), DLB (nine on ChEi, 19 not on ChEi) and PDD (six on ChEi, 31 not on ChEi) comparing 123I-FP-CIT striatal binding (caudate, anterior and posterior putamen) in patients receiving compared with those not receiving ChEi, correcting for key clinical variables including diagnosis, age, sex, Mini-Mental State Examination score, severity of parkinsonism and concurrent antidepressant use.. As previously described, 123I-FP-CIT striatal uptake was lower in DLB and PDD subjects compared with those with AD. Median duration of ChEi use was 180 days. 123I-FP-CIT uptake was not significantly reduced in subjects receiving ChEi compared those not receiving ChEi (mean percentage reduction: AD 4.3%; DLB 0.7%; PDD 6.1%; p = 0.40). ChEi use did not differentially affect striatal 123FP-CIT uptake between patient groups (p = 0.83).. Use of ChEi does not significantly influence the ability of 123I-FP-CIT imaging to distinguish AD from DLB.

Topics: Aged; Alzheimer Disease; Binding Sites; Caudate Nucleus; Cholinesterase Inhibitors; Cross-Sectional Studies; Diagnosis, Differential; Female; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Putamen; Tomography, Emission-Computed, Single-Photon; Tropanes

Dementia with Lewy bodies (DLB) is a common form of dementia. The presence of Alzheimer's disease (AD) pathology modifies the clinical features of DLB, making it harder to distinguish DLB from AD clinically during life. Clinical diagnostic criteria for DLB applied at presentation can fail to identify up to 50% of cases. Our aim was to determine, in a series of patients with dementia in whom autopsy confirmation of diagnosis was available, whether functional imaging of the nigrostriatal pathway improves the accuracy of diagnosis compared with diagnosis by means of clinical criteria alone.. A single photon emission computed tomography (SPECT) scan was carried out with a dopaminergic presynaptic ligand [123I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT; ioflupane) on a group of patients with a clinical diagnosis of DLB or other dementia. An abnormal scan was defined as one in which right and left posterior putamen binding, measured semiquantitatively, was more than 2 SDs below the mean of the controls.. Over a 10 year period it was possible to collect 20 patients who had been followed from the time of first assessment and time of scan through to death and subsequent detailed neuropathological autopsy. Eight patients fulfilled neuropathological diagnostic criteria for DLB. Nine patients had AD, mostly with coexisting cerebrovascular disease. Three patients had other diagnoses. The sensitivity of an initial clinical diagnosis of DLB was 75% and specificity was 42%. The sensitivity of the FP-CIT scan for the diagnosis of DLB was 88% and specificity was 100%.. FP-CIT SPECT scans substantially enhanced the accuracy of diagnosis of DLB by comparison with clinical criteria alone.

Topics: Adult; Aged, 80 and over; Alzheimer Disease; Binding, Competitive; Brain; Brain Stem; Cerebellum; Cohort Studies; Corpus Striatum; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Follow-Up Studies; Humans; Iodine Radioisotopes; Lewy Bodies; Lewy Body Disease; Male; Middle Aged; Neural Pathways; Neurofibrillary Tangles; Occipital Lobe; Sensitivity and Specificity; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Aged; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Cyclohexanols; Depressive Disorder, Major; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Haloperidol; Humans; Lewy Body Disease; Neostriatum; Parkinson Disease, Secondary; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes; Venlafaxine Hydrochloride

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

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

To study the nigrostriatal pathways in 21 patients with dementia with Lewy bodies (DLB), 19 drug naive Parkinson disease (PD) patients, and 16 controls using a dopaminergic presynaptic ligand [123I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) and SPECT in order to assess similarities or differences between DLB and PD.. A SPECT scan was carried out 3 to 4 hours after administration of 185 MBq (IV) of FP-CIT. Using occipital cortex as a radioactivity uptake reference, ratios for the caudate nuclei and the anterior and posterior putamina of both hemispheres were calculated. From the FP-CIT binding measurements, asymmetry indices and caudate:putamen ratios were derived.. The DLB and PD groups had lower FP-CIT binding in all striatal areas than controls (analysis of variance: p < 0.001 in all measures). DLB patients also had significantly lower binding in the caudate nucleus than the PD patients. There was greater asymmetry of uptake in the posterior putamina of PD patients than DLB patients (p < 0.04) and controls (p < 0.01). The mean caudate:putamen ratio for the DLB group was not significantly different from that of the controls, while the mean caudate:putamen ratio of the PD group was higher than that of the control group (p < 0.001) and the DLB group (p < 0.001).. This study showed differences between PD and DLB in the pattern of striatal dopaminergic dysfunction. DLB patients do not have the characteristic selective degeneration of ventrolateral nigral neurons seen in PD. This could explain some of the clinical differences between DLB and PD.

Topics: Caudate Nucleus; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Functional Laterality; Humans; Lewy Body Disease; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Neurologic Examination; Occipital Lobe; Parkinson Disease; Psychiatric Status Rating Scales; Putamen; Severity of Illness Index; Striatonigral Degeneration; Tomography, Emission-Computed, Single-Photon; Tropanes

Dementia with Lewy bodies (DLB) is a common form of late-life dementia that can be difficult to differentiate from other disorders, especially Alzheimer disease (AD), during life. At autopsy the striatal dopaminergic transporter is reduced.. To examine the extent and pattern of dopamine transporter loss using iodine I 123-radiolabeled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) with single-photon emission computed tomography (SPECT) in DLBs compared with other dementias and to assess its potential to enhance a differential diagnosis.. Cohort study comparing FP-CIT with criterion standard of consensus clinical diagnosis.. General hospital.. One hundred sixty-four older subjects (33 healthy older control subjects, 34 with NINCDS/ADRDA [National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association]-confirmed AD, 23 with consensus guideline-confirmed DLB, 38 with United Kingdom's Parkinson Disease Society Brain Bank-confirmed Parkinson disease [PD], and 36 with PD and dementia).. Injection of (123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane with SPECT scan performed at 4 hours.. Visual ratings of scans and region of interest analysis.. Significant reductions (P<.001) in FP-CIT binding occurred in the caudate and anterior and posterior putamens in subjects with DLB compared with subjects with AD and controls. Transporter loss in DLBs was of similar magnitude to that seen in PD, but with a flatter rostrocaudal (caudate-putamen) gradient (P =.001), while the greatest loss in all 3 areas was seen in those who had PD and dementia. Both region of interest analysis and visual ratings provided good separation between DLBs and AD (region of interest: sensitivity, 78%; specificity, 94%; positive predictive value, 90%) but not among subjects with DLB, PD, and PD with dementia.. Dopamine transporter loss can be detected in vivo using FP-CIT SPECT in DLB. Further studies, especially of subjects with DLB without PD, are required to fully establish use in clinical practice.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cohort Studies; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Lewy Body Disease; Male; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

The degeneration of dopaminergic cells in dementia with Lewy bodies (DLB) may provide an important source of additional free radical generation. As a result, the oxidative stress status in DLB could be significantly enhanced. Subsequently, the levels of endogenous antioxidants, which are an indirect measure of free radical activities, may be different in DLB patients when compared with Alzheimer's disease (AD) patients and controls. In this preliminary study, we measured the activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GLU) and total antioxidant capacity in the blood of DLB, AD and control subjects. The state of nigrostriatal dopaminergic system was also assessed in vivo by using a radioactive ligand with an affinity for the dopamine pre-synaptic receptors and by imaging with single-photon emission tomography. Data obtained showed a decrease in dopamine pre-synaptic receptors in all the brain regions of DLB patients. The levels of SOD did not differ significantly between DLB, AD and control subjects. However, GLU levels were significantly higher in the DLB patients when compared with AD patients (p < 0.05) and controls (p < 0.01). CAT blood levels were also higher in DLB when compared with AD, but this did not reach statistical significance. The results suggest that a different oxidative stress state may exist in DLB. This may occur due to increased free radical production from the degeneration of dopaminergic cells and auto-oxidation of dopamine, the availability of which may be maintained in early-stage DLB disease as a result of the compensatory increase in its turnover from the remaining dopaminergic cells.

Topics: Aged; Alzheimer Disease; Antioxidants; Catalase; Corpus Striatum; Female; Free Radicals; Glutathione; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Receptors, Dopamine; Receptors, Presynaptic; Substantia Nigra; Superoxide Dismutase; Tomography, Emission-Computed, Single-Photon; Tropanes

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are the common forms of dementia at post-mortem, but distinguishing between these two types of dementia is often very difficult during life. Ioflupane significantly improves the differentiation during life between DLB and AD patients. However, there is a trend for lower caudate uptake in DLB than PD and lower posterior/caudal putamen uptake in PD than in DLB. Further research is needed to test the hypothesis that dopaminergic degeneration may be different, at least regarding anatomical distribution, in DLB and PD. Furthermore, it is important to consider and discuss the potential for ioflupane in the diagnostic workup of patients with DLB.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Caudate Nucleus; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Humans; Iodine Radioisotopes; Lewy Body Disease; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Neurodegenerative Diseases; Putamen; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

Dementia with Lewy bodies (DLB) is one of the main differential diagnoses of Alzheimer's disease (AD). Key pathological features of patients with DLB are not only the presence of cerebral cortical neuronal loss, with Lewy bodies in surviving neurones, but also loss of nigrostriatal dopaminergic neurones, similar to that of Parkinson's disease (PD). In DLB there is 40-70% loss of striatal dopamine.. To determine if detection of this dopaminergic degeneration can help to distinguish DLB from AD during life.. The integrity of the nigrostriatal metabolism in 27 patients with DLB, 17 with AD, 19 drug naive patients with PD, and 16 controls was assessed using a dopaminergic presynaptic ligand, (123)I-labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane (FP-CIT), and single photon emission tomography (SPET). A SPET scan was carried out with a single slice, brain dedicated tomograph (SME 810) 3.5 hours after intravenous injection of 185 MBq FP-CIT. With occipital cortex used as a radioactivity uptake reference, ratios for the caudate nucleus and the anterior and posterior putamen of both hemispheres were calculated. All scans were also rated by a simple visual method.. Both DLB and PD patients had significantly lower uptake of radioactivity than patients with AD (p<0.001) and controls (p<0.001) in the caudate nucleus and the anterior and posterior putamen.. FP-CIT SPET provides a means of distinguishing DLB from AD during life.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cerebral Cortex; Corpus Striatum; Dominance, Cerebral; Female; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Occipital Lobe; Receptors, Dopamine; Receptors, Presynaptic; Sensitivity and Specificity; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes