Striatal Dopamine Transporter Uptake Research Articles

The Role of Dual-Phase 18 F-FP-CIT PET to Early Diagnosis of Corticobasal Syndrome.

Corticobasal syndrome (CBS) is a neurodegeneration characterized by asymmetric parkinsonism, dystonia, myoclonus, and apraxia. In the early stage, CBS presents with asymmetric parkinsonism and cortical symptoms (apraxia and alien hand), and neuroimaging finding is often vague, making early clinical differentiation from idiopathic Parkinson disease (IPD) challenging. This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter (DAT) uptake using dual-phase FP-CIT PET in discriminating between CBS and IPD at early stage. The study enrolled clinically diagnosed CBS (n = 11) and IPD (n = 22) patients (age and sex matched). All participants underwent dual-phase 18 F-FP-CIT PET, and regional SUV ratio (SUVR) was obtained by semiquantitative analysis. The early perfusion imaging and DAT imaging were compared between groups. The regional SUVRs (early phase) of the frontal lobe, thalamus, cingulate, and caudate were significantly lower in patients with CBS, whereas the SUVR of occipital lobe was lower in the IPD group. The CBS group exhibited more prominent asymmetry than the IPD group, particularly in the perirolandic area, superior frontal gyrus, and anterior parietal lobe in early phase PET. Striatal DAT uptake (delayed phase) revealed that the caudate showed lower SUVR and prominent asymmetry in the CBS group, and the caudate-to-putamen ratio (CP ratio) was significantly lower in CBS patients ( P < 0.001). Among the parameters (early and delayed), the CP ratio in DAT exhibited the most powerful discriminative power from receiver operating characteristic curve comparison (area under curve = 0.983). This study demonstrated that the dual-phase FP-CIT PET is useful in differentiating CBS and IPD in the early stage of the disease, and a lower CP ratio of DAT imaging is highly informative for distinguishing between corticobasal degeneration and IPD.

Prognostic significance of peripheral neutrophils and lymphocytes in early untreated Parkinson’s disease: an 8-year follow-up study

BackgroundTo explore whether peripheral blood neutrophils and lymphocytes are associated with longitudinal motor and cognitive decline in patients with early Parkinson’s disease (PD) and, to uncover the disease-specific mechanisms underlying...

Association between longitudinal changes in striatal dopamine transporter uptake and clinical features of dementia with Lewy bodies.

It is widely known that there is low striatal 123 I-2β-Carbomethoxy-3β-(4-iodophenyl)-N-(3- fluoropropyl) nortropane (123 I-FP-CIT) dopamine transporter single photon emission tomography (DaT-SPECT) uptake in patients with dementia with Lewy bodies (DLB). No studies to date have analyzed the association between longitudinal changes of clinical features and DaT uptake in patients with Parkinson syndrome, particularly those with DLB. The aim of this study was to investigate the association between the longitudinal changes in DaT uptake and the severity of parkinsonism and cognitive function in DLB patients. A total of 35 outpatients with probable DLB who underwent DaT-SPECT twice (at the initial examination and the follow-up period) in the Memory Disorder Clinic at the Department of Geriatric Medicine, Tokyo Medical University, were enrolled in this study between April 2014 and September 2020. The correlation between annual changes in DaT uptake and clinical features (cognitive function decline and parkinsonism) of the patients was analyzed. A significant correlation was detected between annual changes in parkinsonism symptom severity and DaT uptake in the left posterior putamen (r = -0.39, P = 0.03), and between Mini-Mental State Examination scores and DaT uptake in all regions except the right posterior putamen (P < 0.05) in patients with DLB. Our results suggested that the pathway from the ventrolateral tier of the substantia nigra to the putamen might be more crucial for motor function than other pathways, not only in Parkinson's disease but also in DLB.

Striatal Dopamine Transporter Uptake, Parkinsonism, and Cognition in Alzheimer's Disease.

The correlates of motor parkinsonism in Alzheimer's disease (AD) remains controversial. We evaluated the effects of nigrostriatal dopaminergic degeneration on parkinsonism and cognition in biomarker-validated patients with AD. This study recruited 116 patients with AD who underwent dual-phase 18 F-N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane PET, 18 F-Florbetaben PET, 3-Tesla brain MRI, Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests. The mean cortical thickness in the frontal, temporal, parietal, and occipital cortices, and the dopamine transporter (DAT) uptake in the caudate, anterior/posterior putamen, and substantia nigra were quantified. We investigated the relationship between DAT uptake, mean lobar cortical thickness, UPDRS motor score, and cognition using general linear models (GLMs) after controlling for age, sex, education, intracranial volume, and deep and periventricular white matter hyperintensities. A path analysis was performed for the UPDRS motor score with the same covariates. Path analysis and multivariable GLM for UPDRS motor score showed that lower caudate DAT uptake was directly associated with a higher UPDRS motor score, whereas caudate DAT uptake confounded the association between mean frontal/parietal thickness and UPDRS motor score. Multivariable GLMs for cognitive scores showed that lower caudate DAT uptake was associated with visuospatial/executive dysfunction independent of mean frontal or parietal thickness. Nigrostriatal dopaminergic dysfunction is associated with parkinsonism and visuospatial/executive dysfunction in patients with AD.

Glymphatic function assessment in Parkinson's disease using diffusion tensor image analysis along the perivascular space

IntroductionGlymphatic dysfunction can contribute to α-synucleinopathies. We examined glymphatic function in idiopathic Parkinson's disease (PD) utilizing Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS). MethodsThis study enrolled consecutive patients diagnosed with de novo PD between June 2017 and March 2019 who underwent brain DTI with concurrent 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT) SPECT, and age- and sex-matched controls. From DTI-ALPS, the ALPS-index was calculated as a ratio of diffusivities along the x-axis in the region of neural fibers passing vertically to the diffusivities perpendicular to them, which reflected perivascular water motion at the lateral ventricular body level. The ALPS-index of the PD and control groups was compared using Student's t-test; its correlations with clinical scores for motor and cognition (UPDRS-III, MMSE, and MoCA) and striatal dopamine transporter uptake measured by 123I-FP-CIT specific binding ratios (SBRs) were examined using a correlation coefficient. ResultsIn all, 54 patients in the de novo PD group (31 women, 23 men; mean age, 68.9 ± 9.4 years) and 54 in the control group (mean age, 69.0 ± 10.5 years) were included. The ALPS-index was lower in the PD group than in the controls (1.51 ± 0.22 versus 1.66 ± 0.20; P < 0.001). In the PD group, the ALPS-index negatively correlated with the UPDRS-III score (r = −0.526), and positively correlated with the MMSE (r = 0.377) and MoCA scores (r = 0.382) (all, P < 0.05). No correlation was observed between the ALPS-index and striatal 123I-FP-CIT SBRs (P > 0.05). ConclusionsDTI-ALPS can reveal glymphatic dysfunction in patients with PD, whose severity correlated with motor and cognitive dysfunction, but not striatal dopamine transporter uptake.

Neurofilament light chain and cardiac MIBG uptake as predictors for phenoconversion in isolated REM sleep behavior disorder.

Isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD) is considered as a prodromal stage of either multiple system atrophy (MSA) or Lewy body disease (LBD; Parkinson's disease and dementia with Lewy bodies). However, current knowledge is limited in predicting and differentiating the type of future phenoconversion in iRBD patients. We investigated the role of plasma neurofilament light chain (NfL) and cardiac metaiodobenzylguanidine (MIBG) uptake as predictors for phenoconversion. Forty patients with iRBD were enrolled between April 2018 and October 2019 and prospectively followed every 3months to determine phenoconversion to either MSA or LBD. Plasma NfL levels were measured at enrollment. Cardiac MIBG uptake and striatal dopamine transporter uptake were assessed at baseline. Patients were followed for a median of 2.92years. Four patients converted to MSA and 7 to LBD. Plasma NfL level at baseline was significantly higher in future MSA-converters (median 23.2pg/mL) when compared with the rest of the samples (median 14.1pg/mL, p = 0.003). NfL level above 21.3pg/mL predicted phenoconversion to MSA with the sensitivity of 100% and specificity of 94.3%. Baseline MIBG heart-to-mediastinum ratio of LBD-converters (median 1.10) was significantly lower when compared with the rest (median 2.00, p < 0.001). Heart-to-mediastinum ratio below 1.545 predicted phenoconversion to LBD with the sensitivity of 100% and specificity of 92.9%. Plasma NfL and cardiac MIBG uptake may be useful biomarkers in predicting phenoconversion of iRBD. Elevated plasma NfL levels may suggest imminent phenoconversion to MSA, whereas low cardiac MIBG uptake suggests phenoconversion to LBD.

Deep learning regressor model based on nigrosome MRI in Parkinson syndrome effectively predicts striatal dopamine transporter-SPECT uptake

PurposeNigrosome imaging using susceptibility-weightedimaging (SWI) and dopamine transporter imaging using 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT) single-photon emission computerized tomography (SPECT) can evaluate Parkinsonism. Nigral hyperintensity from nigrosome-1 and striatal dopamine transporter uptake are reduced in Parkinsonism; however, quantification is only possible with SPECT. Here, we aimed to develop a deep-learning-based regressor model that can predict striatal 123I-FP-CIT uptake on nigrosome magnetic resonance imaging (MRI) as a biomarker for Parkinsonism.MethodsBetween February 2017 and December 2018, participants who underwent 3 T brain MRI including SWI and 123I-FP-CIT SPECT based on suspected Parkinsonism were included. Two neuroradiologists evaluated the nigral hyperintensity and annotated the centroids of nigrosome-1 structures. We used a convolutional neural network-based regression model to predict striatal specific binding ratios (SBRs) measured via SPECT using the cropped nigrosome images. The correlation between measured and predicted SBRs was evaluated.ResultsWe included 367 participants (203 women (55.3%); age, 69.0 ± 9.2 [range, 39–88] years). Random data from 293 participants (80%) were used for training. In the test set (74 participants [20%]), the measured and predicted 123I-FP-CIT SBRs were significantly lower with the loss of nigral hyperintensity (2.31 ± 0.85 vs. 2.44 ± 0.90) than with intact nigral hyperintensity (4.16 ± 1.24 vs. 4.21 ± 1.35, P < 0.01). The sorted measured 123I-FP-CIT SBRs and the corresponding predicted values were significantly and positively correlated (ρc = 0.7443; 95% confidence interval, 0.6216–0.8314; P < 0.01).ConclusionA deep learning-based regressor model effectively predicted striatal 123I-FP-CIT SBRs based on nigrosome MRI with high correlation using manually-measured values, enabling nigrosome MRI as a biomarker for nigrostriatal dopaminergic degeneration in Parkinsonism.

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?

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. 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)-2β-carboxymethoxy-3β-(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. 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 PETshowed 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. 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.

Prospective Five-Year Follow-Up of Patients with Schizophrenia Suspected with Parkinson's Disease.

Objective It is difficult to distinguish patients with schizophrenia with neuroleptic-induced parkinsonism (NIP) from those with existing idiopathic Parkinson's disease when their striatal dopamine transporter uptake is reduced. There is a possibility of misdiagnosis of Parkinson's disease in patients with schizophrenia as schizophrenia with NIP, which leads to inappropriate treatment. This prospective study aimed at determining the underlying pathophysiology using detailed clinical and psychological assessments. Methods We enrolled six patients with schizophrenia who had parkinsonism and were diagnosed with Parkinson's disease according to the Movement Disorder Society Clinical Diagnostic Criteria, except for the fifth absolute exclusion criteria. Results Five patients had been treated with neuroleptics for 20 years. One patient refused treatment for schizophrenia. All patients had impaired cognitive function at enrolment, olfactory dysfunction, and constipation. All patients were treated with dopaminergic therapy, and their parkinsonism substantially improved; one woman in her 40s experienced a wearing-off effect and dyskinesia. The uptake of dopamine transporter in the striatum decreased by 13%/year during the study period. Conclusion Some patients with schizophrenia and parkinsonism benefit from dopaminergic therapy. Some of these patients may also exhibit Lewy pathology.

Association of plasma α-synuclein with cardiac 123I-MIBG scintigraphy in early Parkinson’s disease

Cardiac 123I-metaiodobenzylguanidine (MIBG) uptake correlates with the extent of cardiac sympathetic denervation found in disease with Lewy pathology, such as Parkinson’s disease (PD). Protein α-synuclein, the main component of Lewy body, is a candidate biomarker of PD, but its relationship with cardiac MIBG uptake has never been explored. Plasma α-synuclein levels were measured in 37 patients with early PD. Cardiac 123I-MIBG scintigraphy and 18F-FP-CIT brain PET were performed, and striatal dopamine transporter (DAT) uptake was quantified using automated segmentation. The relationships of plasma α-synuclein levels with cardiac MIBG and striatal DAT uptake were investigated. The plasma α-synuclein level correlated with early (R = 0.38, P = 0.033) and delayed (R = 0.49, P = 0.0055) MIBG heart-to-mediastinum (H/M) ratios, and its correlation with delayed H/M ratio remained significant after adjustment with age, disease duration, motor severity, and striatal DAT uptake (P = 0.016). The regional SUVRs of any subregions of caudate and putamen did not correlate with plasma α-synuclein level. In the patients with early PD, the plasma α-synuclein level correlated with cardiac sympathetic denervation, but not with nigrostriatal degeneration. This may suggest that plasma α-synuclein levels more readily reflect the peripheral deposition of Lewy bodies than their central deposition.

Implication of metabolic and dopamine transporter PET in dementia with Lewy bodies

To evaluate the implication of 18F-fluorodeoxyglucose (FDG)- and dopamine transporter (DAT)-positron emission tomography (PET) in the diagnosis and clinical symptoms of dementia with Lewy bodies (DLB), 55 DLB patients and 49 controls underwent neuropsychological evaluation and FDG-, DAT-, and 18F-Florbetaben (FBB) PET. DAT- and FDG-uptake and FDG/DAT ratio were measured in the anterior and posterior striatum. The first principal component (PC1) of FDG subject residual profiles was identified for each subject. Receiver operating characteristic curve analyses for the diagnosis of DLB were performed using FDG- and DAT-PET biomarkers as predictors, and general linear models for motor severity and cognitive scores were performed adding FBB standardized uptake value ratio as a predictor. Increased metabolism in the bilateral putamen, vermis, and somato-motor cortices, which characterized PC1, was observed in the DLB group, compared to the control group. A combination of posterior putamen FDG/DAT ratio and PC1 showed the highest diagnostic accuracy (91.8% sensitivity and 96.4% specificity), which was significantly greater than that obtained by DAT uptake alone. Striatal DAT uptake and PC1 independently contributed to motor severity and language, memory, frontal/executive, and general cognitive dysfunction in DLB patients, while only PC1 contributed to attention and visuospatial dysfunction.

Striatal Dopaminergic Deficit and Sleep in Idiopathic Rapid Eye Movement Behaviour Disorder: An Explorative Study.

IntroductionIdiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is increasingly recognised as an important precursor disease state of alpha-synucleinopathies. This parasomnia is characterized by a history of recurrent nocturnal dream enactment behaviour, loss of skeletal muscle atonia, and increased phasic muscle activity during REM sleep. Neuroimaging studies of striatal dopamine transporter uptake tracer signaling suggest increasing dopaminergic deficit across the continuum of the alpha-synucleinopathies, with early sleep dysfunction suggestive of early caudate dysfunction. Henceforth, we set out to investigate the relationship between early sleep changes and the striatal dopaminergic availability in iRBD.MethodsTwelve patients with iRBD, who had undergone a video polysomnography and a neuroimaging assessment of striatal dopamine transporter (DaT) uptake tracer signaling, and 22 matched controls who had similarly undergone a video polysomnography were retrospectively identified. Data were statistically analyzed to identify altered sleep parameters and correlate them with striatal dopamine transporter uptake tracer signaling.ResultsThe iRBD patients exhibited an increased number of periodic limb movements during sleep (P=0.001), compared to 22 age-matched healthy subjects. In addition, several significant links were found between regional DaT-uptakes and sleep architecture. Correlational analyses suggested a strong positive association between sleep fragmentation and dopamine deficiency in left caudate (r=−0.630, P=0.028), whilst an increased uptake in the whole striatum was strongly linked to the sleep efficiency, and to a lesser degree to the length of sleep duration.DiscussionTo the best of our knowledge, this is the first demonstration of a close relationship between dopaminergic availability in striatum and the quality of sleep in iRBD. Taken together, our exploratory findings suggest that subtle but functionally significant striatal changes in early stages of iRBD may contribute to the further shaping of sleep architecture.

Prospective follow up of the patients with Schizophrenia accompanied by Parkinsonism

Objective: Drug-induced parkinsonism (DIP) is a complication of the dopamine receptor block or depletion of dopamine induced parkinsonism. We cannot differentiate the patients with schizophrenia between DIP and Parkinson disease when their striatal dopamine transporter uptake was reduced. We made a report on a detailed clinical and psychological study.

NfL as a biomarker for neurodegeneration and survival in Parkinson disease.

ObjectiveTo determine whether neurofilament light chain protein in CSF (cNfL), a sensitive biomarker of neuroaxonal damage, reflects disease severity or can predict survival in Parkinson disease (PD).MethodsWe investigated whether disease severity, phenotype, or survival in patients with new-onset PD correlates with cNfL concentrations around the time of diagnosis in the population-based New Parkinsonism in Umeå (NYPUM) study cohort (n = 99). A second, larger new-onset PD cohort (n = 194) was used for independent validation. Association of brain pathology with the cNfL concentration was examined with striatal dopamine transporter imaging and repeated diffusion tensor imaging at baseline and 1 and 3 years.ResultsHigher cNfL in the early phase of PD was associated with greater severity of all cardinal motor symptoms except tremor in both cohorts and with shorter survival and impaired olfaction. cNfL concentrations above the median of 903 ng/L conferred an overall 5.8 times increased hazard of death during follow-up. After adjustment for age and sex, higher cNfL correlated with striatal dopamine transporter uptake deficits and lower fractional anisotropy in diffusion tensor imaging of several axonal tracts.ConclusionscNfL shows usefulness as a biomarker of disease severity and to predict survival in PD. The present results indicate that the cNfL concentration reflects the intensity of the neurodegenerative process, which could be important in future clinical trials.Classification of evidenceThis study provides Class II evidence that in patients with PD, cNfL concentrations are associated with more severe disease and shorter survival.

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.

Revised 2017 Clinical Diagnostic Criteria for Dementia with Lewy Bodies: Inclusion of REM Sleep Behavior Disorder and Indicative Biomarkers

Although dementia with Lewy bodies (DLB) is the second most common neurodegenerative disorder after Alzheimer disease, its diagnostic sensitivity in clinical practice is sub-optimal. In 2017, the DLB clinical diagnostic criteria were modified to include the additional core feature of REM sleep behavior disorder (RBD) and three new indicative biomarkers. With this revision, clinically probable DLB is represented by two or more core features (fluctuations, parkinsonism, visual hallucinations, or RBD) or by one core feature plus one indicative biomarker (low striatal dopamine transporter uptake, reduced cardiac [¹²³I]-metaiodobenzylguanidine uptake, or REM sleep without atonia on polysomnography). Because RBD is an early feature of DLB and often precedes the onset of other core features, a clinical history of RBD enables us to improve the low diagnostic sensitivity of DLB at the early stage of disease progression. Moreover, RBD is an accurate predictor of DLB in terms of the differential diagnosis of dementia based on clinicopathological findings. Increasing the detection rate of RBD with confirmation by indicative biomarkers provides greater diagnostic accuracy of DLB, even in the absence of other core features. This review focuses on the revised DLB clinical diagnostic criteria for identifying patients with probable DLB in clinical practice.

Pallidal dopaminergic denervation and rest tremor in early Parkinson's disease: PPMI cohort analysis

Backgrounds: Over recent years there have been some conflicting reports upon the role of pallidal dopaminergic denervation in rest tremor in Parkinson's disease. ObjectivesTo clarify this issue we analyzed the clinical and 123I-FP-CIT SPECT data of a large cohort of early Parkinson's disease patients enrolled in the PPMI study. MethodsPallidal and striatal dopamine transporter uptake ratios were calculated in 382 patients (120 no-tremor, 60 tremor-dominant, and 202 indeterminate) and 150 controls. A region of interest (ROI) approach was used to estimate DAT uptake ratios from 123I-FP-CIT SPECT scans in the caudate nucleus, putamen, and globus pallidus after normalization to a DAT template. DAT uptake ratios for each region were compared between subgroups using ANCOVA and linear regression analyses were performed to evaluate the relationship between severity of rest tremor and regional DAT uptake ratios. ResultsPD patients had significantly lower DAT uptake ratios in the pallidum, putamen and caudate as compared to healthy controls (p < 0.001). ANCOVA showed inter-PD subgroup differences in DAT uptake ratios in the putamen and pallidum (p < 0.05) after adjustment for age and disease duration, with post-hoc comparisons revealing significantly higher DAT uptake ratios for the tremor-dominant subgroup as compared to non-tremor and indeterminate subgroups (p < 0.016). There was no significant relationship between rest tremor severity and pallidal DAT either in the tremor-dominant subgroup or in the total PD population. ConclusionsPallidal dopaminergic denervation appears unrelated to rest tremor severity in early Parkinson's disease.

PITX3 genotype and risk of dementia in Parkinson's disease: A population-based study

Dementia is a devastating manifestation of Parkinson's disease (PD). This study investigates whether a common polymorphism in the PITX3 gene (rs2281983), which is of importance for the function of dopaminergic neurons, affects the risk of developing dementia in PD and whether it affects dopamine transporter (DAT) uptake.We PITX3 genotyped 133 patients with new-onset, idiopathic PD, participating in a population-based study in Sweden. Patients were followed prospectively during 6–11years with extensive investigations, including neuropsychology and DAT-imaging with 123I FP-CIT. The primary outcome was the incidence of PD dementia (PDD), diagnosed according to published criteria, studied by the Kaplan-Meier method and Cox proportional hazards. Performance in individual cognitive domains, the incidence of visual hallucinations, disease progression and striatal DAT uptake on imaging was also investigated.PD patients carrying the PITX3 C allele had an increased risk of developing PDD (hazard ratio: 2.87, 95% CI: 1.42–5.81, p=0.003), compared to the PD patients homozygous for the T-allele. Furthermore, the PITX3 C allele carriers with PD had a poorer cognitive performance in the visuospatial domain (p<0.001) and a higher incidence of visual hallucinations. A trend towards a lower striatal DAT uptake in the PITX3 C allele carriers was suggested, but could not be confirmed.Our results show that a common polymorphism in the PITX3 gene affects the risk of developing PDD and visuospatial dysfunction in idiopathic PD. If validated, these findings can provide new insights into the neurobiology and genetics of non-motor symptoms in PD.

Clinical Characteristics of Parkinson's Disease Developed from Essential Tremor.

Recent genetic and epidemiological studies have shown that there is a link between essential tremor and Parkinson's disease (PD). However, there is a lack of data about the clinical features of PD developed from essential tremor. To explore and describe the clinical characteristics of Parkinson's disease developed from essential tremor (ET-PD). Twenty-five ET-PD patients and 124 IPD controls were enrolled according to each criterion. Motor and non-motor features and dopamine transporter uptake were compared between the two groups. Rest and action tremors were more severe in ET-PD patients than in IPD patients. In addition, tremor disorder of first-degree relatives occurred more frequently in the ET-PD group than in the IPD group. A comparison between cases with ET-PD and IPD was not significant for striatal dopamine transporter uptake. Among the non-motor features, sleep disorder frequency, especially rapid-eye-movement sleep behavioral disorder, were lower in patients with ET-PD than in those with IPD, and smell identification test scores were higher in patients with ET-PD than in those with IPD. The prevalence of other non-motor symptoms did not differ between the two groups. This is the first comparison of motor and non-motor features between ET-PD and IPD. ET-PD and IPD have different characteristic motor and non-motor features from the nosologic perspective.

18F-FP-CIT dopamine transporter PET findings in cirrhotic patients with parkinsonism

We report the clinical features and imaging findings of presynaptic dopamine transporter (DAT) positron emission tomography (PET) in four of patients with liver cirrhosis and concurrent parkinsonism. We also reviewed previously reported cases of cirrhosis-related parkinsonism using dopaminergic molecular imaging.Our results using 18F-radiolabeled N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) DAT PET in four patients with cirrhosis and parkinsonism showed two different molecular imaging patterns well related to their neurological symptoms. 18F-FP-CIT PET imaging of two patients showed normal DAT density in the striatum. Their clinical features included symmetric parkinsonism, early gait disturbances and postural instability, and the absence of resting tremor. The other two patients showed reduced striatal DAT uptake asymmetrically with a rostrocaudal gradient similar to idiopathic Parkinson’s disease (IPD). They had clinical findings of hemiparkinsonism, resting tremor, without early gait disturbance or postural instability. They also showed sustained response to levodopa treatment.Based on the structured review of 21 cases with cirrhosis-related parkinsonism in the literature including the present cases, we categorized cirrhotic parkinsonism into three groups. Eleven of the twenty-one cases were categorized into group 1; levodopa-resistant atypical parkinsonism without a dopaminergic deficit in molecular imaging similar to primary manganism. Another 6 cases were categorized into group 2; coincidental IPD with superimposed cirrhosis with sustained good response to levodopa and presynaptic dopaminergic deficit with rostrocaudal gradient typical of IPD. The other undetermined 4 cases were categorized into group 3. They showed symmetric parkinsonism with variable response to levodopa therapy. Their molecular imaging showed a global diffuse dopaminergic deficit in the presynaptic molecular imaging distinct to group 1 (normal uptake) or 2 (asymmetric rostrocaudal deficit). In conclusion, cirrhosis-related parkinsonism is a heterogeneous disorder.