Dopamine Transporter Imaging Research Articles

Cerebrospinal fluid levels of alpha-synuclein, amyloid β, tau, phosphorylated tau, and neuron-specific enolase in patients with Parkinson’s disease, dementia with Lewy bodies or other neurological disorders: Their relationships with cognition and nuclear medicine imaging findings

Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are common neurodegenerative disorders, but no established biochemical markers for these diseases have been identified. We enrolled 78 subjects (27 patients with PD/DLB, 34 patients with non-PD/DLB neurodegenerative disorders [non-PD/DLB], and 17 controls). Cerebrospinal fluid (CSF) was collected via the standard lumbar puncture technique. The CSF levels of alpha-synuclein, amyloid β40, amyloid β42, tau, phosphorylated tau (p-tau), neuron-specific enolase (NSE), and hemoglobin were measured with enzyme-linked immunosorbent assays. Dopamine transporter imaging with 123I-ioflupane was also performed. The PD/DLB patients exhibited significantly lower CSF alpha-synuclein levels than non-PD/DLB group. Significantly elevated CSF levels of tau, p-tau, and NSE were detected in the non-PD/DLB group. Multivariate analysis revealed that the mini-mental state examination score was correlated with the CSF amyloid β42 level. The specific binding ratio on 123I-ioflupane imaging was decreased in the PD/DLB group, but it was not correlated with the CSF alpha-synuclein level. These results indicate that (1) the CSF alpha-synuclein level is a useful biomarker of PD/DLB; (2) the CSF levels of tau, p-tau, and NSE can be used to discriminate PD/DLB from non-PD/DLB; and (3) the CSF amyloid β42 level is an independent predictor of cognitive decline in neurological disorders.

Clinical and dopamine transporter imaging characteristics of non-manifest LRRK2 and GBA mutation carriers in the Parkinson's Progression Markers Initiative (PPMI): a cross-sectional study

The Parkinson's Progression Markers Initiative (PPMI) is an ongoing observational, longitudinal cohort study of participants with Parkinson's disease, healthy controls, and carriers of the most common Parkinson's disease-related genetic mutations, which aims to define biomarkers of Parkinson's disease diagnosis and progression. All participants are assessed annually with a battery of motor and non-motor scales, 123-I Ioflupane dopamine transporter (DAT) imaging, and biological variables. We aimed to examine whether non-manifesting carriers of LRRK2 and GBA mutations have prodromal features of Parkinson's disease that correlate with reduced DAT binding. This cross-sectional analysis is based on assessments done at enrolment in the subset of non-manifesting carriers of LRRK2 and GBA mutations enrolled into the PPMI study from 33 participating sites worldwide. The primary objective was to examine baseline clinical and DAT imaging characteristics in non-manifesting carriers with GBA and LRRK2 mutations compared with healthy controls. DAT deficit was defined as less than 65% of putamen striatal binding ratio expected for the individual's age. We used t tests, χ2 tests, and Fisher's exact tests to compare baseline demographics across groups. An inverse probability weighting method was applied to control for potential confounders such as age and sex. To account for multiple comparisons, we applied a family-wise error rate to each set of analyses. This study is registered with ClinicalTrials.gov, number NCT01141023. Between Jan 1, 2014, and Jan 1, 2019, the study enrolled 208 LRRK2 (93% G2019S) and 184 GBA (96% N370S) non-manifesting carriers. Both groups were similar with respect to mean age, and about 60% were female. Of the 286 (73%) non-manifesting carriers that had DAT imaging results, 18 (11%) LRRK2 and four (3%) GBA non-manifesting carriers had a DAT deficit. Compared with healthy controls, both LRRK2 and GBA non-manifesting carriers had significantly increased mean scores on the Movement Disorders Society Unified Parkinson's Disease Rating Scale (total score 4·6 [SD 4·4] healthy controls vs 8·4 [7·3] LRRK2 vs 9·5 [9·2] GBA, p<0·0001 for both comparisons) and the Scale for Outcomes for PD - autonomic function (5·8 [3·7] vs 8·1 [5·9] and 8·4 [6·0], p<0·0001 for both comparisons). There was no difference in daytime sleepiness, anxiety, depression, impulsive-compulsive disorders, blood pressure, urate, and rapid eye movement (REM) behaviour disorder scores. Hyposmia was significantly more common only in LRRK2 non-manifesting carriers (69 [36%] of 194 healthy controls vs 114 [55%] of 208 LRRK2 non-manifesting carriers; p=0·0003). Finally, GBA but not LRRK2 non-manifesting carriers showed increased DAT striatal binding ratios compared with healthy controls in the caudate (healthy controls 2·98 [SD 0·63] vs GBA 3·26 [0·63]; p<0·0001), putamen (2·15 [0·56] vs 2·48 [0·52]; p<0·0001), and striatum (2·56 [0·57] vs 2·87 [0·55]; p<0·0001). Our data show evidence of subtle motor and non-motor signs of Parkinson's disease in non-manifesting carriers compared with healthy controls that can precede DAT deficit. Longitudinal data will be essential to confirm these findings and define the trajectory and predictors for development of Parkinson's disease. Michael J Fox Foundation for Parkinson's Research.

Dynamic interaction of genetic risk factors and cocaine abuse in the background of Parkinsonism \u2013 a case report

BackgroundParkinsonism is a complex multifactorial neurodegenerative disorder, in which genetic and environmental risk factors may both play a role. Among environmental risk factors cocaine was earlier ambiguously linked to Parkinsonism. Former single case reports described Parkinsonism in chronic cocaine users, but an epidemiological study did not confirm an increased risk of Parkinson’s disease. Here we report a patient, who developed Parkinsonism in young age after chronic cocaine use, in whom a homozygous LRRK2 risk variant was also detected.Case presentationThe patient was investigated because of hand tremor, which started after a 1.5-year period of cocaine abuse. Neurological examination suggested Parkinsonism, and asymmetrical pathology was confirmed by the dopamine transporter imaging study. The genetic investigations revealed a homozygous risk allele in the LRRK2 gene. After a period of cocaine abstinence, the patient’s symptoms spontaneously regressed, and the dopamine transporter imaging also returned to near-normal.ConclusionsThis case report suggests that cocaine abuse indeed might be linked to secondary Parkinsonism and serves as an example of a potential gene-environmental interaction between the detected LRRK2 risk variant and cocaine abuse. The reversible nature of the DaTscan pathology is a unique feature of this case, and needs further evaluation, whether this is incidental or can be a feature of cocaine related Parkinsonism.

Predicting Progression in Parkinson's Disease Using Baseline and 1-Year Change Measures.

Background:Improved prediction of Parkinson’s disease (PD) progression is needed to support clinical decision-making and to accelerate research trials.Objectives:To examine whether baseline measures and their 1-year change predict longer-term progression in early PD.Methods:Parkinson’s Progression Markers Initiative study data were used. Participants had disease duration ≤2 years, abnormal dopamine transporter (DAT) imaging, and were untreated with PD medications. Baseline and 1-year change in clinical, cerebrospinal fluid (CSF), and imaging measures were evaluated as candidate predictors of longer-term (up to 5 years) change in Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) score and DAT specific binding ratios (SBR) using linear mixed-effects models.Results:Among 413 PD participants, median follow-up was 5 years. Change in MDS-UPDRS from year-2 to last follow-up was associated with disease duration (β= 0.351; 95% CI = 0.146, 0.555), male gender (β= 3.090; 95% CI = 0.310, 5.869), and baseline (β= –0.199; 95% CI = –0.315, –0.082) and 1-year change (β= 0.540; 95% CI = 0.423, 0.658) in MDS-UPDRS; predictors in the model accounted for 17.6% of the variance in outcome. Predictors of percent change in mean SBR from year-2 to last follow-up included baseline rapid eye movement sleep behavior disorder score (β= –0.6229; 95% CI = –1.2910, 0.0452), baseline (β= 7.232; 95% CI = 2.268, 12.195) and 1-year change (β= 45.918; 95% CI = 35.994,55.843) in mean striatum SBR, and 1-year change in autonomic symptom score (β= –0.325;95% CI = –0.695, 0.045); predictors in the model accounted for 44.1% of the variance.Conclusions:Baseline clinical, CSF, and imaging measures in early PD predicted change in MDS-UPDRS and dopamine-transporter binding, but the predictive value of the models was low. Adding the short-term change of possible predictors improved the predictive value, especially for modeling change in dopamine-transporter binding.

Dopamine transporter image in CRMP5 associated autoimmune encephalitis

CRMP5 is one of onco-neuronal antibodies and CRMP5 associated encephalitis has been rarely reported. Various clinical features including chorea, myelitis, visual symptoms and gait disturbance were found. Neither the target of CRMP5 antibodies has been determined, nor dopamine transporter image was reported yet. We report a CRMP5 associated encephalitis showing a reduced uptake in the striatum using FP-CIT. A 69 years-old man was admitted because of involuntary movement. Ten months prior to admission, he started to complain gait instability & choreic movement in head & both limbs. Administration of haloperidol failed to progression of abnormal involuntary movement. On examination, he showed repetitive neck movement, flexion & extension while he was walking. He also showed slow and wide based gait, together with choreic movement in his right hand. Parkinsonian features other than slowness were not noted. In the CSF, mildly elevated protein, but no pleocytosis was found. CRAM5 antibody was positive. MRI revealed widening of both anterior horns of ventricles and ill-defined signal change involving both caudate nucleus heads. FP-CIT dopamine transporter imaging showed severely decreased uptake in both striatum, more prominent in caudate. This is a first report of CRMP5 associated encephalitis showing reduced uptake in the striatum using FP-CIT. This finding suggests CRMP5 antibody may be associated with pathological process in the presynaptic nigrostriatal system, more in the caudate. Larger studies including postmortem will be needed to explore the target of CRMP5 associated encephalitis.

Scintigraphic spectrum of fronto temporal lobar degeneration on FDG PET CT

A retrospective analysis of 40 patients of clinically suspected frontotemporal lobar degeneration, presenting with variable degrees of altered behavior, language, executive control and motor symptoms, was done. All the subjects underwent F-18 FDG PET CT scan of the brain and the studies were analyzed both qualitatively (visually) and semi quantitatively. Few of the subjects also underwent dopamine transporter imaging with Tc 99 m TRODAT 1 on a separate day. The subjects were clinically divided into Behavioral variant fronto temporal dementia (FTD), Non fluent/agrammatic variant primary progressive aphasia (PPA), Semantic variant PPA, Logopenic PPA and FTD with motor symptoms. The FDG uptake patterns were recorded and areas of cortical hypometabolism in the cerebral cortex that were two standard deviations from the mean were considered as abnormal. Behavioral variant subjects, showed diffuse hypometabolism in the medial frontal, Orbital frontal, anterior cingulate and fronto-insular cortices. The subjects with non fluent/agrammatic variant PPA showed predominant left posterior fronto-insular hypometabolism. The subjects with Semantic variant PPA revealed predominant anterior temporal hypometabolism, the Logopenic PPA subjects showed hypometabolism around the angular gyrus and the subjects with motor symptoms showed hypometabolism in the sensorimotor cortices. FDG PET scan may act as a non invasive diagnostic modality in differentiating the myriad clinical and pathologic presentation of fronto temporal lobar degeneration and may help in documenting and characterizing the various overlap syndromes thereby helping in prognosticating the disease process.

Diagnostic imaging of dementia with Lewy bodies, frontotemporal lobar degeneration, and normal pressure hydrocephalus.

Neuroimaging can provide important biomarkers and is very useful for supporting dementia diagnosis. This review summarizes the neuroimaging findings of dementia with Lewy bodies (DLB), frontotemporal lobar degeneration (FTLD), and normal pressure hydrocephalus (NPH). In DLB, medial temporal atrophy is milder than that of Alzheimer's disease. 2-fluoro-2-deoxy-D-glucose-positron emission tomography and brain perfusion single-photon emission computed tomography demonstrate hypometabolism and hypoperfusion in the occipital lobe, in addition to decreased metabolism and perfusion in the parietotemporal, posterior cingulate, precuneus, and frontal association cortices. The cingulate island sign, which shows relatively spared middle-to-posterior cingulate cortex metabolism compared with precuneus hypometabolism, is proposed to detect DLB in 2-fluoro-2-deoxy-D-glucose-positron emission tomography imaging. Reduced uptake in dopamine transporter imaging and reduced myocardial uptake in iodine-123 metaiodobenzylguanidine cardiac scintigraphy are indicative biomarkers for DLB diagnosis. Characteristic findings of FTLD include dominant frontotemporal atrophy, hypometabolism, and hypoperfusion. Most idiopathic NPH cases demonstrate disproportionally enlarged subarachnoid space hydrocephalus findings, including dilated ventricular systems, enlarged Sylvian fissures, tight sulci in the midline, and a high convexity.

DAT imaging and myocardial MIBG scintigraphy for Lewy body diseases: A clinical‐neuroimaging study

AbstractObjectivesNeuroimaging markers for Lewy body diseases (LBDs) include dopamine transporter (DAT) scanning and metaiodobenzylguanidine (MIBG) myocardial scintigraphy. It is unknown which marker is more useful for identifying the three major LBD subtypes: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and the autonomic‐sleep variant. To answer this question, we analyzed clinical‐neuroimaging data of 450 LBD patients.MethodsThis study was a prospective cohort study with a recruiting period of 3.0 years, prospective follow‐up period of 2.0 ± 1.8 years, and visits at least once a year. We recruited 745 referred subjects who had undergone both DAT and MIBG tests, and the inclusion criteria accorded with published criteria of PD, DLB, and the autonomic/sleep variant (at least one of PD/DLB's known early features: orthostatic hypotension, constipation, overactive bladder, and REM sleep behavior disorder [RBD]).ResultsA total of 450 patients fulfilled the criteria. Among the LBD subtypes, the most common was PD (49.3%), followed by DLB (46.4%) and the autonomic/sleep variant (4.2%). DAT and MIBG tests were almost equally abnormal in PD (98.2%, 79.3%, respectively); however, between the two measures, DAT was more frequently abnormal in DLB (82.3%, 56.9%, respectively) and MIBG in the autonomic/sleep variant (57.9%, 94.7%, respectively). Still, these differences did not reach statistical significance.ConclusionBetween the two neuroimaging tests, the DAT scan tended to parallel brain disease (PD/DLB), while the MIBG test tended to parallel peripheral disease (autonomic/sleep variant).

Bilirubin-Related Differential Striatal [18F]FP-CIT Uptake in Parkinson Disease.

Oxidative stress is a leading factor in the pathogenesis of idiopathic Parkinson disease (IPD). Two intrinsic antioxidative molecules, bilirubin and uric acid, are known to protect dopaminergic neurons from oxidative stress in IPD. The objective of this study was to determine the relationship between basal serum levels of 2 molecules and dopaminergic deficit assessed by dopamine transporter imaging with F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane ([F]FP-CIT) PET/CT in patients with early-stage drug-naive IPD. Cases of IPD patients who possess the levels of uric acid and bilirubin within a month from [F]FP-CIT PET/CT from January 2011 to December 2016 were retrospectively reviewed. As a control, the same criteria applied to patients with essential tremor (ET). PET images were analyzed using volume-of-interest templates for 12 striatal subregions and 1 occipital area, and the specific-to-nonspecific binding ratio (SNBR) was calculated. One hundred five patients with drug-naive, early-stage IPD and 62 patients with ET were finally included. Levels of bilirubin were significantly higher in the IPD group than in controls (P = 0.026), and bilirubin level was the factor showing the most correlations with SNBR in IPD (P < 0.001), whereas uric acid showed no such difference or relationship. Furthermore, levels of bilirubin showed a positive correlation with SNBR in more affected posterior putamen in the IPD group (Pearson correlation coefficient, ρ = 0.456; P < 0.001), but a negative one in the ET group (ρ = -0.440, P < 0.001). Bilirubin, not uric acid, was the most significant antioxidant marker for dopaminergic deficit in early-stage drug-naive IPD assessed by [F]FP-CIT PET/CT.

Imaging of dopamine transporter with [18F]LBT-999: initial evaluation in healthy volunteers.

The aim of this study was to evaluate in healthy human brain the distribution, uptake, and kinetics of [18F]LBT-999, a PET ligand targeting the dopamine transporter, to assess its ability to explore dopaminergic innervation, using a shorter protocol, more convenient for patients than currently with [123I]ioflupane. After intravenous injection of [18F]LBT-999, 8 healthy subjects (53-80y) underwent a dynamic PET-scan. Venous samples were concomitantly obtained for metabolites analysis. Time activity curves (TACs) were generated for several ROIs (caudate, putamen, occipital cortex, substantia nigra and cerebellum). Cerebellum was used as reference region to calculate binding potentials (BP<inf>ND</inf>). No adverse events or detectable pharmacological effects were reported. [18F]LBT-999 PET revealed a good cerebral distribution, with an intense and symmetric uptake in both putamen and caudate (BP<inf>ND</inf> of 6.75±1.17 and 6.30±1.17, respectively), without other brain abnormal tracer accumulation. Regional TACs showed a plateau from the maximal uptake, 20min pi, to the end of the acquisition for both caudate and putamen, whereas uptake in substantia nigra decreased progressively. A faster clearance and lowest BP<inf>ND</inf> values were observed in both cortex and cerebellum. Ratios to the cerebellum exhibit value of about 3 in substantia nigra, close to 10 for both caudate and putamen, and remained around the value of 1 in cortex. The parent fraction of [18F]LBT-999 in plasma was 80%, 60% and 45% at 15, 30 and 45 min pi, respectively. These findings support the usefulness of [18F]LBT-999 for a quantitative clinical evaluation of presynaptic dopaminergic innervation.

Molecular Imaging of the Dopamine Transporter.

Dopamine transporter (DAT) single-photon emission tomography (SPECT) with (123)Ioflupane is a widely used diagnostic tool for patients with suspected parkinsonian syndromes, as it assists with differentiating between Parkinson’s disease (PD) or atypical parkinsonisms and conditions without a presynaptic dopaminergic deficit such as essential tremor, vascular and drug-induced parkinsonisms. Recent evidence supports its utility as in vivo proof of degenerative parkinsonisms, and DAT imaging has been proposed as a potential surrogate marker for dopaminergic nigrostriatal neurons. However, the interpretation of DAT-SPECT imaging may be challenged by several factors including the loss of DAT receptor density with age and the effect of certain drugs on dopamine uptake. Furthermore, a clear, direct relationship between nigral loss and DAT decrease has been controversial so far. Striatal DAT uptake could reflect nigral neuronal loss once the loss exceeds 50%. Indeed, reduction of DAT binding seems to be already present in the prodromal stage of PD, suggesting both an early synaptic dysfunction and the activation of compensatory changes to delay the onset of symptoms. Despite a weak correlation with PD severity and progression, quantitative measurements of DAT binding at baseline could be used to predict the emergence of late-disease motor fluctuations and dyskinesias. This review addresses the possibilities and limitations of DAT-SPECT in PD and, focusing specifically on regulatory changes of DAT in surviving DA neurons, we investigate its role in diagnosis and its prognostic value for motor complications as disease progresses.

Longitudinal analyses of cerebrospinal fluid α-Synuclein in prodromal and early Parkinson's disease.

BackgroundAggregation of α-synuclein is central to the pathophysiology of PD. Biomarkers related to α-synuclein may be informative for PD diagnosis/progression.ObjectivesTo analyze α-synuclein in CSF in drug-naïve PD, healthy controls, and prodromal PD in the Parkinson’s Progression Markers Initiative.MethodsOver up to 36-month follow-up, CSF total α-synuclein and its association with MDS-UPDRS motor scores, cognitive assessments, and dopamine transporter imaging were assessed.ResultsThe inception cohort included PD (n = 376; age [mean {standard deviation} years]: 61.7 [9.62]), healthy controls (n = 173; age, 60.9 [11.3]), hyposmics (n = 16; age, 68.3 [6.15]), and idiopathic rapid eye movement sleep behavior disorder (n = 32; age, 69.3 [4.83]). Baseline CSF α-synuclein was lower in manifest and prodromal PD versus healthy controls. Longitudinal α-synuclein decreased significantly in PD at 24 and 36 months, did not change in prodromal PD over 12 months, and trended toward an increase in healthy controls. The decrease in PD was not shown when CSF samples with high hemoglobin concentration were removed from the analysis. CSF α-synuclein changes did not correlate with longitudinal MDS-UPDRS motor scores or dopamine transporter scan.ConclusionsCSF α-synuclein decreases early in the disease, preceding motor PD. CSF α-synuclein does not correlate with progression and therefore does not reflect ongoing dopaminergic neurodegeneration. Decreased CSF α-synuclein may be an indirect index of changes in the balance between α-synuclein secretion, solubility, or aggregation in the brain, reflecting its overall turnover. Additional biomarkers more directly related to α-synuclein pathophysiology and disease progression and other markers to be identified by, for example, proteomics and metabolomics are needed.

Neuropathologic correlates of amyloid and dopamine transporter imaging in Lewy body disease.

To develop imaging biomarkers of diseases in the Lewy body spectrum and to validate these markers against postmortem neuropathologic findings. Four cognitively normal participants with Parkinson disease (PD), 4 with PD with cognitive impairments, and 10 with dementia with Lewy bodies underwent amyloid imaging with [11C]Pittsburgh compound B (PiB) and dopamine transporter (DAT) imaging with [11C]Altropane. All 18 had annual neurologic examinations. All cognitively normal participants with PD developed cognitive impairment before death. Neuropathologic examinations assessed and scored Braak Lewy bodies, Thal distribution of amyloid, Consortium to Establish a Registry for Alzheimer's Disease neuritic amyloid plaques, Braak neurofibrillary tangles, and cerebral amyloid angiopathy, as well as total amyloid plaque burden in the superior frontal, superior parietal, occipital, and inferior temporal cortical regions. PET data were expressed as the standardized uptake value ratio with cerebellar reference. Analyses accounted for the interval between imaging and autopsy. All 18 patients met neuropathologic criteria for Lewy body disease; the DAT concentration was low in each case. All patients with elevated [11C]PiB retention measured in a neocortical aggregate had β-amyloid deposits at autopsy. [11C]PiB retention significantly correlated with neuritic plaque burden and with total plaque burden. [11C]PiB retention also significantly correlated with the severity of both Braak stages of neurofibrillary tangle and Lewy body scores. Neuritic plaque burden was significantly associated with neurofibrillary tangle pathology. Antemortem [11C]Altropane PET is a sensitive measure of substantia nigra degeneration. [11C]PiB scans accurately reflect cortical amyloid deposits seen at autopsy. These findings support the use of molecular imaging in the evaluation of patients with Lewy body diseases.

No link between striatal dopaminergic axons and dopamine transporter imaging in Parkinson's disease.

Brain dopamine transporter binding has been considered a possible biomarker for nigrostriatal degeneration in PD. To investigate whether dopamine transporter binding is associated with the number of dopaminergic neurites in the putamen. Tyrosine hydroxylase-positive nerve fibers were counted from postmortem putamen sections taken from 14 parkinsonism patients who had been scanned with dopamine transporter single-photon emission computed tomography antemortem. Fiber counts were correlated with putamen dopamine transporter binding and SN neuron counts. The putamen dopamine transporter specific binding ratio did not correlate with the putamen tyrosine hydroxylase-positive axon counts (r = 0.00; P = 1.0; PD patients: r = 0.07; P = 0.86). The nigra neuron counts had a positive correlation with the putamen tyrosine hydroxylase-positive axon counts. Striatal dopamine transporter imaging does not associate with axonal nor somal loss of the nigrostriatal neurons in PD. It may reflect dopaminergic activity rather than number of surviving neurons or their striatal projection axons. © 2019 International Parkinson and Movement Disorder Society.

Clinical profiles of late-onset psychiatric patients exhibiting incidental REM sleep without atonia.

Rapid eye movement (REM) sleep without atonia (RWA), which is a hallmark of REM sleep behavior disorder (RBD) on polysomnography (PSG), may represent specific characteristics of prodromal Parkinson's disease (PD)/dementia with Lewy bodies (DLB), even when dream-enactment behavior is absent. We investigated the clinical profiles associated with PD/DLB in late-onset psychiatric patients exhibiting incidental RWA. Among patients who underwent PSG in our psychiatric ward, eight with incidental RWA, nine with idiopathic RBD, and seven with PD or DLB who had preceding RBD were included. Clinical variables, including the percentage of RWA in the total REM sleep (%RWA), were compared among the three groups. The frequency of depressive disorders as a primary psychiatric diagnosis and antidepressant usage were significantly higher in the incidental RWA group than in the other groups. There were no differences in the prevalence of supportive features of DLB among the three groups. The median %RWA was significantly lower in the incidental RWA group than in the other groups. Although the cardiac 123I-metaiodobenzylguanidine uptake was significantly higher in the incidental RWA group compared with the other groups, the groups showed overlap in the specific binding ratios on dopamine transporter imaging. All patients in the three groups exhibited cingulate island sign ratios on brain perfusion single-photon emission computed tomography within a threshold of 0.281, which is the optimal cut-off value for a diagnosis of DLB. In this series, late-onset psychiatric patients with incidental RWA partially shared common clinical profiles with idiopathic RBD and PD/DLB.

Effect of brain atrophy in quantitative analysis of 123I-ioflupane SPECT.

Dopamine transporter (DAT) imaging such as 123I-ioflupane (123I-FP-CIT) SPECT is a useful tool for the diagnosis of parkinsonism and dementia. The Southampton method is the quantitative method for evaluating 123I-FP-CIT SPECT and is less affected by the partial volume effect of the striatum. The method may be vulnerable to contamination by low-uptake areas of cerebrospinal fluid in whole brain, and the threshold of voxel value (threshold method, TM) was developed to correct the contamination. The purpose of this study is to evaluate the TM in the patients with neurological disease. We studied 99 subjects, including 39 patients with Alzheimer's disease (AD), 15 patients with Parkinson's disease (PD) and 10 patients with dementia with Lewy bodies (DLB). Each subject had undergone 123I-FP-CIT SPECT. We calculated the SBR with and without the TM. The SBR laterality was assessed using the asymmetry index (AI). We investigated the relationship between the SBR change with TM and brain atrophy, which were assessed using Evans index (EI), sylvian index (SI) and cerebral atrophy index (CAI). Cutoff value for EI was 0.3, and cutoff values for SI and CAI were the first quartile, respectively. The SBR with TM was 0.53 percentage points lower than the SBR without TM overall (p < 0.01). Positive and negative reversal of AI increased with age. The rate of the SBR change with TM was tended to be lower in groups with brain atrophy. The number of voxels excluded by TM in striatal volumes of interest (VOIs) was larger with high groups for EI, SI and CAI than in low groups. The number of voxels excluded using TM in reference VOIs was related to SI. The SBR was decreased using TM. The effect of TM on the SBR tended to be small in the subjects with severe brain atrophy. The effect of brain atrophy in the TM is larger in the striatal VOIs than in the reference VOIs. Even if quantitative analyses are available, visual assessment of 123I-FP-CIT SPECT is essential for diagnosis.

Revision of Diagnosis in Early Parkinsonism with Abnormal Dopamine Transporter Imaging.

In patients with early parkinsonism, misdiagnosis may occur in >30% of cases. This can have detrimental consequences clinically and in clinical trials. Dopamine transporter (DAT) SPECT imaging can help improve diagnostic accuracy. To describe characteristics of individuals initially diagnosed with idiopathic Parkinson's disease (iPD) and with abnormal DAT SPECT imaging who had a change in diagnosis on follow-up. Data were obtained from the biomarker study Parkinson's Progression Markers Initiative (PPMI). PPMI is a multicenter, observational study that enrolled 423 individuals with a diagnosis of iPD of ≤2 years duration and with abnormal DAT SPECT imaging. Participants were assessed at least annually, and diagnosis was documented by the site neurologist. Characteristics of those that had a change in diagnosis were compared to those with stable diagnosis. 390 subjects were included. Eight (2%) had a change in diagnosis. The diagnosis was changed to multiple system atrophy in 5 cases, dementia with Lewy bodies in 2, and corticobasal degeneration in 1. Revision of diagnosis occurred 2-5.2 years from enrollment. Mean motor score was higher (26.9 vs 20.6; p = 0.01), DAT binding lower (1.056 vs 1.406; p = 0.01), genetic risk score lower (-0.016 vs -0.022; p = 0.0470), and olfaction score higher (28.75 vs 22.05; p = 0.03) in those whose diagnosis changed compared to those who did not. Diagnosis remained stable in most individuals with early parkinsonism diagnosed with iPD and with abnormal DAT imaging. A small number had a revision in diagnosis. Clinical and biomarker abnormalities were greater at baseline in those whose diagnosis changed.

Reduced Uptake on Dopamine Transporter Imaging by Methylphenidate

Reduced Uptake on Dopamine Transporter Imaging by Methylphenidate

パーキンソン病と膀胱障害 ─ドパミン・トランスポーター画像を含めて─

パーキンソン病と膀胱障害 ─ドパミン・トランスポーター画像を含めて─

Wearable sensor (Parkinson’s Kinetigraph) and dopamine transporter imaging as potential biosignature for constipation in Parkinson’s (P2.8-006)

Wearable sensor (Parkinson’s Kinetigraph) and dopamine transporter imaging as potential biosignature for constipation in Parkinson’s (P2.8-006)