Dual-phase 18 F-FP-CIT positron emission tomography and cardiac 123 I-MIBG scintigraphy of Parkinson's disease patients with GBA mutations: evidence of the body-first type?

BACKGROUND AND PURPOSE: Parkinson's disease (PD) with glucocerebrosidase (GBA) gene mutation (GBA-PD) is known to show more rapid clinical progression than sporadic PD without GBA mutation (sPD). This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter uptake and cardiac meta-iodobenzylguanidine (MIBG) uptake of GBA-PD in comparison to sPD. METHODS: Through next-generation sequencing analysis targeting 41 genes, a total of 16 GBA-PD and 24 sPD patients (sex, age matched) were enrolled in the study, and the clinical, dual-phase [18 F]-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane (1 8 F-FP-CIT) positron emission tomography (PET) and cardiac 123 I-MIBG scintigraphy results were compared between the two groups. RESULTS: The GBA-PD group had higher rates of rapid eye movement sleep behavior disorder, orthostatic hypotension and neuropsychiatric symptoms than the sPD group. Early-phase 18 F-FP-CIT PET showed significantly lower standard uptake value ratio on bilateral posterior parietal cortex (0.94 ± 0.05 vs. 1.02 ± 0.04, p = 0.011) and part of the occipital cortex (p < 0.05) in the GBA-PD group than the sPD group. In striatal dopamine transporter uptake, the regional standard uptake value ratio, asymmetry index and caudate-to-putamen ratio were similar between the two groups. The GBA-PD group had a lower heart-to-mediastinum uptake ratio in 123 I-MIBG scintigraphy than the sPD group. CONCLUSIONS: The GBA-PD patients showed decreased regional perfusion in the bilateral posterior parietal and occipital cortex. Cardiac sympathetic denervation and non-motor symptoms (orthostatic hypotension, rapid eye movement sleep behavior disorder) were more common in GBA-PD than sPD. These findings suggest that GBA-PD patients have more widespread peripheral (extranigral) α-synuclein accumulation, representing a body-first PD subtype.

Is the cingulate island sign a marker for early dementia conversion in Parkinson's disease?

BACKGROUND: To investigate whether the cingulate island sign (CIS) ratio (i.e., the ratio of regional uptake in the posterior cingulate cortex relative to the precuneus and cuneus on cerebral perfusion scans) is associated with early dementia conversion in Parkinson's disease (PD). METHODS: We enrolled 226 patients with newly diagnosed PD and 48 healthy controls who underwent dual-phase 18 F-FP-CIT PET scans. Patients with PD were classified into three groups according to the CIS ratio on early-phase 18 F-FP-CIT PET images: a PD group with CIS or high CIS ratios (PD-CIS; n = 96), a PD group with inverse CIS or low CIS ratios (PD-iCIS; n = 40), and a PD group consisting of the remaining patients with normal CIS ratios (PD-nCIS; n = 90). We compared the risk of dementia conversion within a 5-year time point between the groups. RESULTS: There were no significant differences in age, sex, education, or baseline cognitive function between the PD groups. The PD-CIS group had higher Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and more severely decreased dopamine transporter availability in the putamen. The PD-iCIS group had a smaller hippocampal volume compared with the other groups. The risk of dementia conversion in the PD-CIS group did not differ from that in the PD-iCIS and PD-nCIS groups. Meanwhile, the PD-iCIS group had a higher risk of dementia conversion than the PD-nCIS group. CONCLUSION: The results of this study suggest that inverse CIS, rather than CIS, is relevant to early dementia conversion in patients with PD.

Unsupervised clustering of dopamine transporter PET imaging discovers heterogeneity of parkinsonism.

Parkinsonism has heterogeneous nature, showing distinctive patterns of disease progression and prognosis. We aimed to find clusters of parkinsonism based on 18 F-fluoropropyl-carbomethoxyiodophenylnortropane (FP-CIT) PET as a data-driven approach to evaluate heterogenous dopaminergic neurodegeneration patterns. Two different cohorts of patients who received FP-CIT PET were collected. A labeled cohort (n = 94) included patients with parkinsonism who underwent a clinical follow-up of at least 3 years (mean 59.0 ± 14.6 months). An unlabeled cohort (n = 813) included all FP-CIT PET data of a single-center. All PET data were clustered by a dimension reduction method followed by hierarchical clustering. Four distinct clusters were defined according to the imaging patterns. When the diagnosis of the labeled cohort of 94 patients was compared with the corresponding cluster, parkinsonism patients were mostly included in two clusters, cluster "0" and "2." Specifically, patients with progressive supranuclear palsy were significantly more included in cluster 0. The two distinct clusters showed significantly different clinical features. Furthermore, even in PD patients, two clusters showed a trend of different clinical features. We found distinctive clusters of parkinsonism based on FP-CIT PET-derived heterogeneous neurodegeneration patterns, which were associated with different clinical features. Our results support a biological underpinning for the heterogeneity of neurodegeneration in parkinsonism.

Detailed visual assessment of striatal dopaminergic depletion in patients with idiopathic normal pressure hydrocephalus: unremarkable or not?

BACKGROUND: Dopamine transporter (DAT) imaging may enable clinicians to discriminate idiopathic normal pressure hydrocephalus (iNPH) from other parkinsonian disorders. However, a specific pattern of dopaminergic loss in DAT imaging of iNPH patients remains to be further elucidated. METHODS: In this preliminary study, 11 patients with iNPH in our hospital between March 2017 and February 2019 were finally enrolled. A diagnosis of iNPH was made according to the two established criteria. For visual analysis of DAT imaging, a striatum was divided into five domains. A semi-quantitative visual assessment was performed with a consensus between a nuclear medicine specialist and an experienced neurologist who were blinded to the clinical diagnosis. RESULTS: Striatal dopaminergic deficits were abnormal in 90.9% (10/11) of patients with iNPH. The degree of dopaminergic reduction was mild and heterogeneous. However, a tendency of preferential striatal DAT loss in the caudate nucleus (90.9%, 10/11) than in the putamen (72.7%, 8/11) was observed, whereas ventral portion (9.1%, 1/11) was relatively preserved. CONCLUSION: Striatal dopaminergic depletion might be mild and heterogeneous in patients with iNPH. These dopaminergic deficits were more common in the caudate nucleus than in the putamen, suggesting a pattern different from other degenerative parkinsonian disorders.

A case report of adult-onset Alexander disease clinically presenting as Parkinson's disease: is the comorbidity associated with genetic susceptibility?

BACKGROUND: Alexander disease is a rare neurological disease characterized by progressive spastic quadriparesis and bulbar palsy. Moreover, certain patients with adult-onset Alexander disease were often misdiagnosed as other neurodegenerative disorders. CASE PRESENTATION: Herein, we report an adult a 58-year-old woman presented with typical parkinsonism with good levodopa-responsiveness. The patient's dopamine transporter scanning showed significant striatal depletion, while her brain magnetic resonance imaging revealed bilateral tadpole shape of medulla oblongata and bilateral high signal intensity at both cerebellar dentate nuclei in T2-weighted images, suggesting the possibility of a genetic disorder beyond Parkinson's disease. The patient's genetic test resulted in known pathogenic glial fibrillary acidic protein variant, indicating Alexander disease. CONCLUSION: This unique case highlights genetically diagnosed Alexander disease may present with clinical Parkinson's disease.

Lack of association between dopamine transporter loss and non-motor symptoms in patients with Parkinson's disease: a detailed PET analysis of 12 striatal subregions.

INTRODUCTION: Patients with Parkinson's disease (PD) present a variety of non-motor symptoms. However, it remains unclear whether dopamine depletion is related to non-motor symptoms, and which non-motor symptoms are significantly dependent on dopaminergic deficit. METHODS: Forty-one patients with PD who underwent positron emission tomography imaging of dopamine transporters (DATs) were recruited for this study. The striatum was divided into 12 subregions, and DAT activity, as striatal dopaminergic concentration, was calculated in each subregion. In addition to measuring motor symptoms using the Unified Parkinson's Disease Rating Scale-part III (UPDRS-III), various non-motor symptoms were assessed using the Montreal cognitive assessment, frontal assessment battery, Beck depression inventory (BDI), Beck anxiety inventory, PD sleep scale (PDSS), PD fatigue scale, and non-motor symptoms scale (NMSS) for PD. RESULTS: For simple linear regression analyses, dopaminergic depletion in all striatal subregions was negatively correlated with the UPDRS-III score. The most relevant non-motor symptom assessment related to dopaminergic loss in the 12 subregions was NMSS, followed by BDI and PDSS. However, following multiple linear regression analyses, dopaminergic depletion in the 12 striatal subregions was not related with any of the non-motor symptoms. Conversely, dopaminergic deficit in the right anterior and posterior putamen was associated with the UPDRS-III score. CONCLUSIONS: Striatal dopaminergic depletion was not significantly correlated with any of the various non-motor symptoms in PD. Our findings suggest that non-dopaminergic systems are significantly implicated in the pathogenesis of non-motor symptoms in patients with PD.

The role of 18F-FP-CIT PET in differentiation of progressive supranuclear palsy and frontotemporal dementia in the early stage.

PURPOSE: The purpose of this study was to evaluate whether the pattern of striatal dopamine transporter (DAT) availability could differentiate between progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD) in the first few years of the disease. METHODS: We enrolled patients who had Parkinsonism and frontal dysfunction and/or language deficit, visited the clinic within 2 years of the onset of symptoms, and had been followed-up for longer than 5 years; thus resulting in 26 patients with PSP and 24 patients with FTD. By quantitatively analyzing N-(3-[18F]fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane PET, we compared the pattern of DAT availability at the time of the baseline evaluation between the two groups. The discriminatory power of variables including DAT activity and clinical parameters was investigated by receiver operating characteristics (ROC) analyses. Additionally, we analyzed the correlation between striatal subregional DAT availability and cognitive profiles. RESULTS: Patients with PSP and FTD had significantly lower DAT availability than normal controls in the whole striatum and in each striatal subregion. When comparing the two groups, DAT availability was significantly lower in patients with PSP than those with FTD in all striatal subregions. The PSP and FTD groups had generally similar subregional patterns of DAT activity in terms of the anteroposterior and ventrodorsal gradients and asymmetry, except for a different preferential involvement in the caudate. The ROC analysis showed that the DAT activity of the whole striatum had an excellent discriminatory power relative to Parkinsonism or neurocognitive profiles. Correlation analysis showed that verbal memory was significantly correlated with DAT availability in the whole striatum and the putaminal subregion only in patients with PSP. CONCLUSIONS: DAT scans have prognostic value in determining whether patients with Parkinsonism and behavioral and/or language dysfunction will develop features of PSP or FTD later in the disease course.

An FP-CIT PET comparison of the difference in dopaminergic neuronal loss in subtypes of early Parkinson's disease.

BACKGROUND: Patients with tremor-dominant Parkinson's disease (PD) have slower disease progression, show less cognitive decline, and have more favorable outcomes than patients with non-tremor PD. However, the pathophysiology of PD tremor remains unclear. Whether there are differences in nigrostriatal dopaminergic dysfunction between the two PD subtypes is unknown. PURPOSE: To evaluate the differences in regional dopamine transporter (DAT) density in the brain between different subtypes of early PD using FP-CIT PET/CT. MATERIAL AND METHODS: We recruited 43 patients with PD (21 tremor-dominant PD [TP] and 22 non-tremor-dominant PD [NTP]) and 18 age-matched healthy controls. All patients with PD underwent FP-CIT PET/CT imaging and evaluated Parkinsonian motor severity by using the Hoehn and Yahr stage and Part III of the Unified Parkinson's Disease Rating Scale (UPDRS). We also compared tremor and non-tremor symptoms with motor phenotype scores between two subtypes of PD. RESULTS: All patients with PD demonstrated a significantly decreased FP-CIT uptake in the putamen compared to healthy controls. Differences in putamen FP-CIT uptake versus caudate nucleus FP-CIT uptake in PD showed putamen uptake was significantly more impaired than that in the caudate nucleus. However, there was no significant difference in FP-CIT uptake in the striatum between both PD groups at the same early stage of disease. CONCLUSION: We suggest that differential of DAT uptake in the striatum did not allow for a reliable separation of subtypes into tremor-dominant and non-tremor-dominant, especially in the early stages of PD. Therefore, we assumed that many systems besides the nigrostriatal dopaminergic system are involved in the generation of tremors in PD.

Patterns of regional cerebral hypoperfusion in early Parkinson's disease: Clinical implications.

INTRODUCTION: This study aimed to investigate whether regional cerebral perfusion patterns on early-phase 18F-FP-CIT PET scans, which is typically coupled to cerebral metabolism, predict the long-term prognosis of Parkinson's disease (PD). METHODS: We enrolled 397 drug-naïve patients with early-stage PD who underwent dual-phase 18F-FP-CIT PET scans. After quantifying the early-phase 18F-FP-CIT PET images, cluster analysis was performed to delineate the PD subtypes according to the patterns of regional cerebral perfusion. We compared the risk of developing levodopa-induced dyskinesia (LID), wearing-off, freezing of gait (FOG), and dementia between the PD subtypes. RESULTS: Cluster analysis classified patients into three subtypes: cluster 1 (relatively preserved cortical uptake; n = 175), cluster 2 (decreased uptake in the frontal, parietal, and temporal regions; n = 151), and cluster 3 (decreased uptake in more extensive regions, additionally involving the lateral occipital regions; n = 71). Cluster 1 was characterized by a younger age-of-onset, less severe motor deficits, less severely decreased 18F-FP-CIT binding in the caudate, and better cognitive performance. Cluster 3 was characterized by an older age-of-onset, more severe motor deficits, and poorer cognitive performance. Cluster 2 was intermediate between clusters 1 and 3. Cox regression analyses demonstrated that clusters 2 and 3 had a higher risk for dementia conversion than cluster 1, whereas the risk for developing LID, wearing-off, and FOG did not differ among the clusters. CONCLUSION: The patterns of regional cerebral perfusion can provide information on long-term prognosis with regards to cognitive, but not motor aspects of patients with early-stage PD.

Salivary Gland Uptake on 18F-FP-CIT PET as a New Biomarker in Patients With Parkinsonism.

OBJECTIVE: 18F-FP-CIT positron emission tomography (PET) is known for its high sensitivity and specificity for evaluating striatal dopamine transporter (DAT) binding. Recently, for the early diagnose of Parkinson's disease, many researchers focused on the diagnosis of synucleinopathy in organs involved in non-motor symptoms of Parkinson's disease. We investigated the feasibility of salivary gland uptake on 18F-FP-CIT PET as a new biomarker in patients with parkinsonism. MATERIALS AND METHODS: A total of 219 participants with confirmed or presumed parkinsonism, including 54 clinically diagnosed idiopathic Parkinson's disease (IPD), 59 suspected and yet undiagnosed, and 106 with secondary parkinsonism, were enrolled. The standardized uptake value ratio (SUVR) of the salivary glands was measured on both early and delayed 18F-FP-CIT PET scans using the cerebellum as the reference region. Additionally, the delayed-to-early ratio (DE_ratio) of salivary gland was obtained. The results were compared between patients with different PET patterns. RESULTS: The SUVR in early 18F-FP-CIT PET scan was significantly higher in patients with IPD pattern compared that in the non-dopaminergic degradation group (0.5 ± 0.19 vs. 0.6 ± 0.21, P < 0.001). Compared with the non-dopaminergic degradation group, the DE_ratio was significantly lower in patients with IPD (5.05 ± 1.7 vs. 4.0 ± 1.31, P < 0.001) or atypical parkinsonism patterns (5.05 ± 1.7 vs. 3.76 ± 0.96, P < 0.05). The DE_ratio was moderately and positively correlated with striatal DAT availability in both the whole striatum (r = 0.37, P < 0.001) and posterior putamen (r = 0.36, P < 0.001). CONCLUSION: Parkinsonism patients with an IPD pattern exhibited a significant increase in uptake on early 18F-FP-CIT PET and a decrease in the DE_ratio in the salivary gland. Our findings suggest that salivary gland uptake of dual-phase 18F-FP-CIT PET can provide diagnostic information on DAT availability in patients with Parkinson's disease.

Diagnostic Performance for Differential Diagnosis of Atypical Parkinsonian Syndromes from Parkinson's Disease Using Quantitative Indices of 18F-FP-CIT PET/CT.

We are aimed to evaluate the diagnostic performances of quantitative indices obtained from dual-phase 18F-FP-CIT PET/CT for differential diagnosis of atypical parkinsonian syndromes (APS) from Parkinson's disease (PD). We analyzed 172 subjects, including 105 non-Parkinsonism, 26 PD, 8 PSP, 1 CBD, 8 MSA-P, 9 MSA-C, and 15 DLB retrospectively. Two sequential PET/CT scans were acquired at 5 min and 3 h. We compared subregional binding potentials, putamen-to-caudate nucleus ratio of the binding potential, asymmetry index, and degree of washout. To differentiate APS, all BPs in both early and late phases (except late BPbrainstem) and all factors of the percent change except for putamen in APS significantly differed from PD. When a cut-off for early BPcerebellum was set as 0.79, the sensitivity, specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy for differentiating APS 73.2%, 91.7%, 93.8%, 66.7%, and 80.0%. The early BPcerebellum showed significantly greater SP and PPV than the late quantitative indices. Combined criteria regarding both early and late indices exhibited only greater NPV. The quantitative indices showed high diagnostic performances in differentiating APS from PD. Our findings provide the dual-phase 18F-FP-CIT PET/CT would be useful for differentiating APS from PD.

Differential diagnosis of patients with atypical Parkinsonian syndrome using 18F-FDG and 18F-FP CIT PET: A report of five cases.

We describe 5 cases of patients who presented atypical parkinsonian syndrome (APS), including gait disturbance, postural instability, decreasing facial expression, dyskinesia, and subjective cognitive impairment. The patients underwent 18F-FP-CIT PET and 18F-FDG PET consecutively for differential diagnosis of APS. Through PET imaging examination, it was possible to offer a suggestive diagnosis and determine individual strategic management for patients with APS.

Test-retest reproducibility of dopamine transporter density measured with [18F]FP-CIT PET in patients with essential tremor and Parkinson's disease.

OBJECTIVE: 18F-labeled fluoropropyl-carbomethoxylodopropyl-nor-ß-tropane ([18F]FP-CIT) positron emission tomography (PET) is a useful tool for evaluating disease progression in Parkinson's disease (PD) patients. We evaluated the test-retest reproducibility of [18F]FP-CIT PET measures in essential tremor (ET) and PD patients. METHODS: Fifteen ET (68.9 ± 6.6 years) and 10 PD patients (70.5 ± 6.3 years; Hoehn and Yahr stage, 2.3 ± 0.8) underwent two [18F]FP-CIT PET/CT scans with an interval of 48 ± 7 day. For both the test and retest studies, standardized uptake value ratios were estimated for 90-min and 3-h acquisitions for the caudate, anterior putamen, and posterior putamen using T1-MRI-based normalization (automatic) and fixed-VOI (manual) methods, with the occipital lobe as a reference. Reproducibility was evaluated by the bias, variability, percent test-retest, within-subject coefficient of variation, repeatability coefficient, and intraclass correlation coefficient (ICC). RESULTS: Reproducibility was excellent, with low variability (ET: 6.99-8.02%, PD: 3.51-6.94%) and high reliability (ICC; ET: 0.88-0.96, PD: 0.98-0.99). The ET group showed higher variability and lower ICCs than the PD group. The variability in the 90-min images (ET: 7.85-8.59%, PD: 1.52-2.75%) was comparable to that in the 3-h images (ET: 6.99-8.02%, PD: 3.51-6.94%). There were no differences in variability among the subregions in the ET group. In the PD group, the variability was high in the posterior putamen (automatic method: 6.94%, manual method: 11.80%). The test-retest variability and ICCs were similar for the manual and automatic methods. CONCLUSION: [18F]FP-CIT PET is reproducible for the quantitative measurement of DAT binding in both ET and PD individuals, independent of the acquisition time or analysis method. Also, the automatic method is more suitable for evaluating early loss of DAT binding in patients with PD.

Presynaptic dopaminergic function in early-onset Alzheimer's disease: an FP-CIT image study.

We aimed to investigate whether amyloid-ß (Aß) positive early-onset Alzheimer's disease (EOAD) patients have presynaptic dopaminergic deficits on in vivo 18F-FP-CIT PET imaging. We enrolled 34 EOAD patients and 9 cognitively normal controls (NC), all of whom underwent 18F-florbetaben and 18F-FP-CIT PET at Samsung Medical Center. We assessed motor symptoms using Unified Parkinson's Disease Rating Scale (UPDRS) and divided the EOAD patients into 2 groups using a UPDRS cutoff of 10. We compared regional florbetaben and FP-CIT uptake across the NC and the 2 EOAD groups with lower and higher UPDRS and investigated the associations between regional florbetaben or FP-CIT uptake and UPDRS in EOAD patients. Among the 30 EOAD patients who were Aß positive on florbetaben PET, the higher UPDRS (>10) group (n = 9) had a longer disease duration (7.2 ± 3.3 vs. 4.1 ± 1.8, p = 0.002), and had a tendency to have lower Mini-Mental State Examination (9.6 ± 7.9 vs. 15.0 ± 6.0, p = 0.052) than the lower UPDRS (≤10) group (n = 21). Across the NC and the 2 EOAD groups, there were no significant differences in FP-CIT uptake in caudate (p = 0.122) and putamen (p = 0.685) or florbetaben uptake in midbrain (p = 0.890). Finally, regression analyses showed that UPDRS was not associated with FP-CIT uptake in caudate (p = 0.913) or putamen (p = 0.407), or with florbetaben PET uptake in caudate (p = 0.553), putamen (p = 0.617), midbrain (p = 0.843), or global cortex (p = 0.658). This study showed that parkinsonian signs in EOAD patients may be related with mechanisms other than presynaptic dopaminergic deficit. Our finding is clinically important because it suggests that L-dopa treatment in EOAD with parkinsonian signs may not improve motor symptoms.

Spatial Normalization Using Early-Phase [18F]FP-CIT PET for Quantification of Striatal Dopamine Transporter Binding.

PURPOSE: The precise quantification of dopamine transporter (DAT) density on N-(3-[18F]Fluoropropyl)-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane positron emission tomography ([18F]FP-CIT PET) imaging is crucial to measure the degree of striatal DAT loss in patients with parkinsonism. The quantitative analysis requires a spatial normalization process based on a template brain. Since the spatial normalization method based on a delayed-phase PET has limited performance, we suggest an early-phase PET-based method and compared its accuracy, referring to the MRI-based approach as a gold standard. METHODS: A total of 39 referred patients from the movement disorder clinic who underwent dual-phase [18F]FP-CIT PET and took MRI within 1 year were retrospectively analyzed. The three spatial normalization methods were applied for quantification of [18F]FP-CIT PET-MRI-based anatomical normalization, PET template-based method based on delayed PET, and that based on early PET. The striatal binding ratios (BRs) were compared, and voxelwise paired t tests were implemented between different methods. RESULTS: The early image-based normalization showed concordant patterns of putaminal [18F]FP-CIT binding with an MRI-based method. The BRs of the putamen from the MRI-based approach showed higher agreement with early image- than delayed image-based method as presented by Bland-Altman plots and intraclass correlation coefficients (early image-based, 0.980; delayed image-based, 0.895). The voxelwise test exhibited a smaller volume of significantly different counts in putamen between brains processed by early image and MRI compared to that between delayed image and MRI. CONCLUSION: The early-phase [18F]FP-CIT PET can be utilized for spatial normalization of delayed PET image when the MRI image is unavailable and presents better performance than the delayed template-based method in quantitation of putaminal binding ratio.

Dopa Responsive Parkinsonism in an Early Onset Alzheimer's Disease Patient with a Presenilin 1 Mutation (A434T).

Alzheimer's disease patients with presenilin 1 (PSEN1) mutations commonly show parkinsonism in addition to dementia. Yet, whether these patients show dopaminergic deficit and response to L-dopa is largely unknown. We report a 43-year-old woman with a PSEN1 mutation (A434T) who showed right side dominant parkinsonism. As disease progressed, she developed bilateral parkinsonism which was markedly relieved by L-dopa. Amyloid (Florbetaben) positron-emission tomography (PET) showed cortical florbetaben uptake, relatively sparing the striatum. Initial dopamine transporter (FP-CIT) PET showed asymmetrically decreased FP-CIT uptake in the left striatum. We suggest that in Alzheimer's disease patients with PSEN1 mutation, parkinsonism may be relieved by L-dopa when it is associated with presynaptic dopaminergic deficit.

Longitudinal Decline of Striatal Subregional [18F]FP-CIT Uptake in Parkinson's Disease.

PURPOSE: Dopamine transporter imaging is suggested to be a useful imaging biomarker for Parkinson's disease (PD) progression and monitoring drug effects. We investigated the longitudinal decline characteristics of striatal [18F]FP-CIT uptake in PD. METHODS: We retrospectively reviewed 35 PD patients and 9 non-PD patients. All patients underwent [18F]FP-CIT PET at the initial diagnosis and follow-up. PET images were spatially normalized and analyzed with eight striatal and one occipital VOI templates. We measured the specific to non-specific binding ratio (SNBR) of the striatal subregions and calculated the absolute annual reduction (AAR) and relative annual reduction (%RAR) of the SNBRs. RESULTS: Total striatal SNBRs in PD patients were significantly lower than those in non-PD patients, with the most significant difference in the posterior putamen. Both AAR (0.26 ± 0.14 vs. 0.09 ± 0.19, p < 0.05) and %RAR (6.9 ± 3.5 vs. 1.2 ± 2.7, p < 0.001) of total striatal SNBRs were significantly greater in PD than non-PD patients. There were no significant differences in the AAR and %RAR of total striatal SNBRs between elderly and young onset PD. The AARs of the posterior putamen were higher in early PD than in advanced PD. Conversely, the %RARs were not significantly different between early and more advanced PD. The disease duration was significantly negatively correlated with the AAR but not with the %RAR of the posterior putamen. CONCLUSIONS: The longitudinal decline of striatal [18F]FP-CIT uptake in PD was nonlinear and significantly faster than that in non-PD, with a different rate of decline among the striatal subregions.

Is Parkinson's Disease with History of Agent Orange Exposure Different from Idiopathic Parkinson's Disease?

BACKGROUND AND PURPOSE: During Vietnam War, many Korean soldiers were dispatched to fight in the war where they were exposed to Agent Orange. Until now, there exist only limited evidence on existence of association between exposure to Agent Orange and Parkinson's disease (PD). To elucidate the effects of Agent Orange exposure on PD, we compared the clinical characteristics and radiolabeled 18F-FP-CIT PET uptake between patients with Agent Orange exposure and patients with Agent Orange no-exposure. METHODS: We retrospectively evaluated 143 patients exposed to Agent Orange and 500 patients with no exposure to Agent Orange from our movement clinics database. The differences between clinical characteristics and pattern of 18F-FP-CIT PET uptake were investigated. RESULTS: Among Unified Parkinson's Disease Rating Scale III motor subscales, tremor at rest, rigidity, finger taps, and rapid alternating movement was significantly higher in patients exposed to Agent Orange as compared to patients with no exposure to Agent Orange. The facial expression score was significantly lower in patients exposed to Agent Orange as compared to patients with no exposure to Agent Orange. Compared to patients not exposed to Agent Orange, all basal ganglia areas (contra- and ipsilateral caudate nucleus, anterior putamen, and posterior putamen) showed a lower18F-FP-CIT uptake and higher asymmetry index of anterior and posterior putamen was found in patients exposed to Agent Orange. The caudate/putamen ratio was significantly lower in patients exposed to Agent Orange as compared to patients with no exposure to Agent Orange. CONCLUSIONS: This study showed a different clinical profile and FP-CIT PET findings between patients exposed to Agent Orange as compared to patients with no exposure to Agent Orange. This finding suggests the possibility of different pathophysiology of PD in patients exposed to Agent Orange from idiopathic PD.