Search

Compensatory mechanisms in Parkinson's disease are defined as the changes that the brain uses to adapt to neurodegeneration and progressive dopamine reduction. Motor compensation in early Parkinson's disease could, in part, be responsible for a unilateral onset of clinical motor signs despite the presence of bilateral nigrostriatal degeneration. Although several mechanisms have been proposed for compensatory adaptations in Parkinson's disease, the underlying pathophysiology is unclear. Here, we investigate motor compensation in Parkinson's disease by investigating the relationship between clinical signs, dopamine transporter imaging data and neurophysiological measures of the primary motor cortex (M1), using transcranial magnetic stimulation in presymptomatic and symptomatic hemispheres of patients. In this cross-sectional, multicentre study, we screened 82 individuals with Parkinson's disease. Patients were evaluated clinically in their medication OFF state using standardized scales. Sixteen Parkinson's disease patients with bilateral dopamine transporter deficit in the putamina but unilateral symptoms were included. Twenty-eight sex- and age-matched healthy controls were also investigated. In all participants, we tested cortical excitability using single- and paired-pulse techniques, interhemispheric inhibition and cortical plasticity with paired associative stimulation. Data were analysed with ANOVAs, multiple linear regression and logistic regression models. Individual coefficients of motor compensation were defined in patients based on clinical and imaging data, i.e. the motor compensation coefficient. The motor compensation coefficient includes an asymmetry score to balance motor and dopamine transporter data between the two hemispheres, in addition to a hemispheric ratio accounting for the relative mismatch between the magnitude of motor signs and dopaminergic deficit. In patients, corticospinal excitability and plasticity were higher in the presymptomatic compared with the symptomatic M1. Also, interhemispheric inhibition from the presymptomatic to the symptomatic M1 was reduced. Lower putamen binding was associated with higher plasticity and reduced interhemispheric inhibition in the presymptomatic hemisphere. The motor compensation coefficient distinguished the presymptomatic from the symptomatic hemisphere. Finally, in the presymptomatic hemisphere, a higher motor compensation coefficient was associated with lower corticospinal excitability and interhemispheric inhibition and with higher plasticity. In conclusion, the present study suggests that motor compensation involves M1–striatal networks and intercortical connections becoming more effective with progressive loss of dopaminergic terminals in the putamen. The balance between these motor networks seems to be driven by cortical plasticity. [ABSTRACT FROM AUTHOR]

Purpose: [123I]I-FP-CIT SPECT is an imaging tool to support the diagnosis of parkinsonian syndromes characterized by nigrostriatal dopaminergic degeneration. After intravenous injection, [123I]I-FP-CIT is metabolized for a small part by the enzyme CYP3A4, leading to the formation of [123I]I-nor-β-CIT. [123I]I-nor-β-CIT passes the blood-brain barrier and has a very high affinity for the serotonin transporter (SERT). The SERT is expressed in the striatum and cortical areas. So, at least theoretical, the use of frequently used CYP3A4 inhibitors (like amiodarone) may influence the specific to non-specific striatal [123I]I-FP-CIT ratio. Here we tested this novel hypothesis. Methods: Using a retrospective design, we determined the specific to non-specific striatal [123I]I-FP-CIT ratio (using BRASS software) in 6 subjects that were using an CYP3A4 inhibitor and 18 matched controls. Only subjects were included with a normal rated [123I]I-FP-CIT SPECT scan, and all participants were scanned on the same brain-dedicated SPECT system. Results: The specific to non-specific (assessed in the occipital cortex) striatal [123I]I-FP-CIT binding ratio was significantly higher in CYP3A4 users than in the control group (3.52 ± 0.33 vs. 2.90 ± 0.78, p < 0.001). Conclusion: Our preliminary data suggest that the use of CYP3A4 inhibitors may influence striatal [123I]I-FP-CIT binding ratios. This information, when reproduced in larger studies, may be relevant for studies in which quantification of [123I]I-FP-CIT SPECT imaging is used for diagnostic or research purposes. [ABSTRACT FROM AUTHOR]

Background: Dementia with Lewy bodies (DLB) presents with various symptoms, posing challenges for early diagnosis challenging. Dopamine transporter (123I-FP-CIT) single-photon emission tomography (SPECT) and 123I-meta-iodobenzylguanidine (123I-MIBG) imaging are crucial diagnostic biomarkers. Hypothesis about body- and brain-first subtypes of DLB indicate that some DLB may show normal 123I-FP-CIT or 123I-MIBG results; but the characteristic expression of these two subtypes remains unclear. Objective: This study aimed to evaluate the diagnostic sensitivity of 123I-FP-CIT and 123I-MIBG imaging alone, combined in patients with DLB and explore symptoms associated with the abnormal imaging results. Methods: Demographic data, clinical status, and imaging results were retrospectively collected from patients diagnosed with possible DLB. Both images were quantified using semi-automated software, and the sensitivity of each imaging modality and their combination was calculated. Demographic data, cognition, and motor and non-motor symptoms were compared among the subgroups based on the imaging results. Symptoms related to each imaging abnormality were examined using binomial logistic regression analyses. Results: Among 114 patients with DLB, 80 underwent 123I-FP-CIT SPECT (sensitivity: 80.3%), 83 underwent 123I-MIBG imaging (68.2%), and 66 both (sensitivity of either abnormal result: 93.9%). Visual hallucinations differed among the four subgroups based on imaging results. Additionally, nocturia and orthostatic hypotension differed between abnormal and normal 123I-MIBG images. Conclusions: Overall, 123I-FP-CIT SPECT was slightly higher sensitivity than 123I-MIBG imaging, with combined imaging increasing diagnostic sensitivity. Normal results of a single imaging test may not refute DLB. Autonomic symptoms may lead to abnormal 123I-MIBG scintigraphy findings indicating body-first subtype of patients with DLB. [ABSTRACT FROM AUTHOR]

Research criteria for the diagnosis of prodromal dementia with Lewy bodies (DLB) include three clinical subtypes: mild cognitive impairment with Lewy bodies (MCI‐LB), delirium‐onset prodromal DLB, and psychiatric‐onset prodromal DLB. Late‐onset psychiatric manifestations are at a higher risk of developing dementia, but its relation to prodromal DLB remains unclear. In addition to the risk of severe antipsychotic hypersensitivity reactions, accurate discrimination from non‐DLB cases is important due to the potential differences in management and prognosis. This article aims to review a rapidly evolving psychiatric topic and outline clinical pictures of psychiatric‐onset prodromal DLB, including the proposed biomarker findings of MCI‐LB: polysomnography‐confirmed rapid eye movement sleep behaviour disorder, cardiac [123I]metaiodobenzylguanidine scintigraphy, and striatal dopamine transporter imaging. We first reviewed clinical pictures of patients with autopsy‐confirmed DLB. Regarding clinical reports, we focused on the patients who predominantly presented with psychiatric manifestations and subsequently developed DLB. Thereafter, we reviewed clinical studies regarding the diagnostic applications of the proposed biomarkers to patients with late‐onset psychiatric disorders. Clinical presentations were mainly late‐onset depression and psychosis; however, other clinical manifestations were also reported. Psychotropic medications before a DLB diagnosis may cause extrapyramidal signs, and potentially influences the proposed biomarker findings. These risks complicate clinical manifestation interpretation during the management of psychiatric symptoms. Longitudinal follow‐up studies with standardised evaluations until conversion to DLB are needed to investigate the temporal trajectories of core features and proposed biomarker findings. In patients with late‐onset psychiatric disorders, identification of patients with psychiatric‐onset prodromal DLB provides the opportunity to better understanding the distinct prognostic subgroup that is at great risk of incident dementia. Advances in the establishment of direct biomarkers for the detection of pathological α‐synuclein may encourage reorganising the phenotypic variability of prodromal DLB. [ABSTRACT FROM AUTHOR]

N-3-[18F]fluoropropyl-2β-carbomethoxy-3β-4-iodophenyl nortropane ([18F]FP-CIT) is a radiopharmaceutical for dopamine transporter (DAT) imaging using positron emission tomography (PET) to detect dopaminergic neuronal degeneration in patients with parkinsonian syndrome. [18F]FP-CIT was granted approval by the Ministry of Food and Drug Safety in 2008 as the inaugural radiopharmaceutical for PET imaging, and it has found extensive utilization across numerous institutions in Korea. This review article presents an imaging procedure for [18F]FP-CIT PET to aid nuclear medicine physicians in clinical practice and systematically reviews the clinical studies associated with [18F]FP-CIT PET. [ABSTRACT FROM AUTHOR]

Objective: Impulse control behaviors (ICBs) frequently coexist with Parkinson’s disease (PD). However, the predictors of ICBs in PD remain unclear, and there is limited data on the biological correlates of ICBs in PD. In this study, we examined clinical, imaging, and biological variables to identify factors associated with longitudinal changes in ICBs in early-stage PD. Methods: The data for this study were obtained from the Parkinson’s Progression Markers Initiative, an international prospective cohort study that evaluates markers of disease progression in PD. We examined clinical, imaging, and biological variables to determine their associations with ICBs over a period of up to 5  years. Cox regression models were employed to investigate the predictors of ICBs in early-stage, untreated PD. Results: The study enrolled 401 individuals with PD and 185 healthy controls (HC). At baseline, 83 PD subjects (20.7%) and 36 HC (19.5%) exhibited ICBs. Over the course of 5 years, the prevalence of ICBs increased in PD (from 20.7% to 27.3%, p < 0.001), while it decreased in HC (from 19.5% to 15.2%, p < 0.001). Longitudinally, the presence of ICBs in PD was associated with depression, anxiety, autonomic dysfunction, and excessive daytime sleepiness (EDS). However, there was no significant association observed with cognitive dysfunction or motor severity. Treatment with dopamine agonists was linked to ICBs at years 3 and 4. Conversely, there was no association found between ICBs and presynaptic dopaminergic dysfunction. Additionally, biofluid markers in baseline and the first year did not show a significant association with ICBs. A predictive index for ICBs was generated, incorporating three baseline characteristics: anxiety, rapid eye movement sleep behavior disorder (RBD), and p-tau levels in cerebrospinal fluid (CSF). Conclusion: During the early stages of PD, there is a notable increase in ICBs over time. These ICBs are associated with depression, anxiety, autonomic dysfunction, EDS, and the use of dopaminergic medications, particularly dopamine agonists. Anxiety, RBD, and p-tau levels in CSF are identified as predictors for the incident development of ICBs in early PD. Further longitudinal analyses will provide a more comprehensive understanding of the associations between ICBs and imaging findings, as well as biomarkers. These analyses will help to better characterize the relationships and implications of these factors in the context of ICBs in early PD. [ABSTRACT FROM AUTHOR]

Purpose: Nigrosome imaging using susceptibility-weighted imaging (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. Methods: Between 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. Results: We 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). Conclusion: A 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. [ABSTRACT FROM AUTHOR]

Purpose: In routine practice, dopamine transporter (DAT) imaging is frequently used as a diagnostic tool to support the diagnosis of Parkinson's disease or dementia with Lewy bodies. In 2008, we published a review on which medications and drugs of abuse may influence striatal [123I]I-FP-CIT binding and consequently may influence the visual read of an [123I]I-FP-CIT SPECT scan. We made recommendations on which drugs should be withdrawn before performing DAT imaging in routine practice. Here, we provide an update of the original work based on published research since 2008. Methods: We performed a systematic review of literature without language restriction from January 2008 until November 2022 to evaluate the possible effects of medications and drugs of abuse, including the use of tobacco and alcohol, on striatal DAT binding in humans. Results: The systematic literature search identified 838 unique publications, of which 44 clinical studies were selected. Using this approach, we found additional evidence to support our original recommendations as well as some new findings on potential effect of other medications on striatal DAT binding. Consequently, we updated the list of medications and drugs of abuse that may influence the visual read of [123I]I-FP-CIT SPECT scans in routine clinical practice. Conclusion: We expect that a timely withdrawal of these medications and drugs of abuse before DAT imaging may reduce the incidence of false-positive reporting. Nevertheless, the decision to withdraw any medication must be made by the specialist in charge of the patient's care and considering the pros and cons of doing so. [ABSTRACT FROM AUTHOR]

Background: Studies of glymphatic dysfunction in Parkinson's disease (PD) patients have attracted much attention in recent years. However, the relationships between glymphatic dysfunction and clinical symptoms remains unclear. Objectives: To determine whether the diffusion tensor image analysis along the perivascular space (DTI-ALPS) affect the severity and types of motor and non-motor symptoms in PD patients. Methods: De novo PD patients and controls who performed both DTI and 123I-DaTscan single photon emission computed tomography (SPECT) scanning were retrieved from the international multicenter Parkinson's Progression Marker Initiative (PPMI) cohort. Glymphatic system was evaluated by the DTI-ALPS. Motor symptoms were assessed by Movement Disorders Society Unified Parkinson's Disease Rating Scale III (MDS-UPDRS-III). The influence of glymphatic activity on motor and non-motor symptoms was explored by multivariate linear regression models. Results: A total of 153 PD patients (mean age 60.97 ± 9.47 years; 99 male) and 67 normal controls (mean age 60.10 ± 10.562 years; 43 male) were included. The DTI-ALPS index of PD patients was significantly lower than normal controls (Z = − 2.160, p = 0.031). MDS-UPDRS III score (r = − 0.213, p = 0.008) and subscore for rigidity (r = − 0.177, p = 0.029) were negatively correlated with DTI-ALPS index. The DTI-ALPS index was significantly associated with MDS-UPDRS-III score (β = − 0.160, p = 0.048) and subscore for rigidity (β = − 0.170, p = 0.041) after adjusting for putamen dopamine transporter availability and clinical factors. Conclusions: Our results showed distinct relationships between glymphatic dysfunction and the severity and types of PD motor symptoms, suggesting the potential of DTI-ALPS index as a biomarker for PD motor symptoms. [ABSTRACT FROM AUTHOR]

Introduction : Differential diagnosis between Parkinson's disease (PD) and multiple system atrophy–parkinsonian type (MSA-P), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), collectively termed atypical Parkinsonism (AP), is challenging. Dopamine transporter density imaging with Ioflupane I123 (DaTscan) is a marker of presynaptic nigrostriatal dysfunction. The primary aim of this study was to investigate the utility of DaTscan in the differential diagnosis of MSA-P, CBD, and PSP. Methods: Patients examined at Eginition Hospital (2011–2021), with available DaTscan data and a diagnosis of probable AP, clinically established PD, as well as a neurological control (NC) group were included. Mean binding specific index (BSI), BSI of the most affected side, asymmetry index, laterality, and caudate/putamen ratio were recorded. Analyses were performed by Kruskal-Wallis and ANCOVA. Results: 137 patients were included (CBD: n = 28 ; MSA-P: n = 15 ; PSP: n = 42 ; PD: n = 17 ; NC: n = 35 ). There were significant differences when comparing CBS, PSP, and NC vs. all other groups combined. Pairwise between-group comparisons revealed significant differences between PSP and CBD (mean striatum BSI>1.95; sensitivity 74.1%; specificity 85.0%), CBD and MSA-P (mean striatum BSI>2.04; sensitivity 70.4%; specificity 86.7%), and CBD and PD (mean striatum BSI>2.11; sensitivity 66.7%; specificity 100.0%). There were no differences between PSP, MSA-P, and PD. PSP, MSA-P, and PD differed from NC subjects, with 100% specificity and high sensitivity. Differentiation of NC from CBD was suboptimal. Discussion: CBD patients exhibit relatively mild DaTscan abnormalities. DaTscan may assist in the differentiation of CBD from PSP. DaTscan does not differentiate among PD, MSA-P, and PSP. [ABSTRACT FROM AUTHOR]

Objective(s): The purpose of this study was to validate undersampled single-photon emission computed tomography (SPECT) imaging using a combination of compressed sensing (CS) iterative reconstruction (CS-IR) and offset acquisition.Methods: Three types of numerical phantoms were used to evaluate image quality and quantification derived from CS with offset acquisition. SPECT images were reconstructed using filtered back-projection (FBP), maximum likelihood-expectation maximization (ML-EM), CS-IR, and CS-IR with offset acquisition. The efficacy of CS-IR with offset acquisition was examined in terms of spatial resolution, aspect ratio (ASR), activity concentration linearity, contrast, percent coefficient of variation (%CV), and specific binding ratio (SBR).Results: The full widths at half maximum remained unchanged as the number of projections decreased in CS-IR with offset acquisition. Changes in ASRs and linearities of count density were observed for ML-EM and CS-IR from undersampled projections. The %CV obtained by CS-IR with offset acquisition was substantially lower than that obtained by ML-EM and CS-IR. There were no significant differences between the %CVs obtained from 60 projections by CS-IR with offset acquisition and from 120 projections by FBP. Although the SBRs for CS-IR with offset acquisition tended to be slightly lower than for FBP, the SBRs for CS-IR with offset acquisition did not change with the number of projections.Conclusions: CS-IR with offset acquisition can provide good image quality and quantification compared with a commonly used SPECT reconstruction method, especially from undersampled projection data. Our proposed method could shorten overall SPECT acquisition times, which would benefit patients and enable quantification with dynamic SPECT acquisitions.

A case study of a 69-year-old woman developed depressive mood with appetite loss, apathy, insomnia, agitation, decreased ability of concentration, fatigue, dyspnea, and thoughts of suicide, is presented. Topics include clinical profiles during two depressive episodes at hospitalization and discuss the potential predictors of higher risk of developing dementia with Lewy bodies (DLB); and dimer brain perfusion single-photon emission computed tomography showed localised occipital hypoperfusion.

Purpose : This work attempts to decode the discriminative information in dopamine transporter (DAT) imaging using deep learning for the differential diagnosis of parkinsonism. Methods: This study involved 1017 subjects who underwent DAT PET imaging ([11C]CFT) including 43 healthy subjects and 974 parkinsonian patients with idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA) or progressive supranuclear palsy (PSP). We developed a 3D deep convolutional neural network to learn distinguishable DAT features for the differential diagnosis of parkinsonism. A full-gradient saliency map approach was employed to investigate the functional basis related to the decision mechanism of the network. Furthermore, deep-learning-guided radiomics features and quantitative analysis were compared with their conventional counterparts to further interpret the performance of deep learning. Results: The proposed network achieved area under the curve of 0.953 (sensitivity 87.7%, specificity 93.2%), 0.948 (sensitivity 93.7%, specificity 97.5%), and 0.900 (sensitivity 81.5%, specificity 93.7%) in the cross-validation, together with sensitivity of 90.7%, 84.1%, 78.6% and specificity of 88.4%, 97.5% 93.3% in the blind test for the differential diagnosis of IPD, MSA and PSP, respectively. The saliency map demonstrated the most contributed areas determining the diagnosis located at parkinsonism-related regions, e.g., putamen, caudate and midbrain. The deep-learning-guided binding ratios showed significant differences among IPD, MSA and PSP groups (P < 0.001), while the conventional putamen and caudate binding ratios had no significant difference between IPD and MSA (P = 0.24 and P = 0.30). Furthermore, compared to conventional radiomics features, there existed average above 78.1% more deep-learning-guided radiomics features that had significant differences among IPD, MSA and PSP. Conclusion: This study suggested the developed deep neural network can decode in-depth information from DAT and showed potential to assist the differential diagnosis of parkinsonism. The functional regions supporting the diagnosis decision were generally consistent with known parkinsonian pathology but provided more specific guidance for feature selection and quantitative analysis. [ABSTRACT FROM AUTHOR]

Background: Multiple pathologies may underlie corticobasal syndrome (CBS), including Alzheimer's disease (AD). Dopamine transporter density imaging with Ioflupane 123 I SPECT (DaTscan) may be normal in CBS. No studies to date have examined the relationship between DaTscan status and underlying pathology in CBS. Objectives: The main objective of the study was to test whether a normal DaTscan in CBS patients is indicative of an underlying AD pathology, as determined by cerebrospinal fluid (CSF) biomarkers. Methods: Eighteen CBS patients were included. They were divided into patients with an AD and a non‐AD disease pathology, based on their cerebrospinal fluid biochemical profile. A typical AD CSF profile was defined as an increase in total and phosphorylated at threonine 181 tau protein in addition to a decrease in amyloid‐beta with 42 amino acids. DaTscan data were compared in these two groups. Results: Eight of the 18 CBS patients (44%) had a normal DaTscan. Seven of the 18 CBS patients (39%) had an AD cerebrospinal fluid biochemical profile. Two of seven CBS patients with AD biomarker profile had abnormal DaTscans. Three of 11 CBS patients with a non‐AD biomarker profile had normal DaTscans. A normal DaTscan was indicative of AD pathology with suboptimal (~70%) sensitivity and specificity. Semi‐quantitative DaTscan analysis did not differentiate between AD from non‐AD CSF biomarker profile in CBS. Conclusion: A normal DaTscan is indicative of AD in CBS, but the sensitivity and specificity of DaTscan as an in vivo marker of AD pathology is suboptimal. [ABSTRACT FROM AUTHOR]

Accurate diagnosis of idiopathic normal pressure hydrocephalus is important to manage patients with idiopathic normal pressure hydrocephalus more appropriately. Based on the clinical features and brain magnetic resonance imaging findings, the idiopathic normal pressure hydrocephalus diagnosis is made up. However, most clinicians do not recommend the shunt operation to their patients with presumed idiopathic normal pressure hydrocephalus unless any patients with idiopathic normal pressure hydrocephalus show a considerable improvement through the cerebrospinal fluid tap test. The cerebrospinal fluid tap test is an invasive method and has some limitations to diagnose idiopathic normal pressure hydrocephalus. Therefore, we suppose that a new diagnostic approach of idiopathic normal pressure hydrocephalus is necessary. Various magnetic resonance imaging findings suggesting idiopathic normal pressure hydrocephalus have been applied to diagnose idiopathic normal pressure hydrocephalus. Besides, advances in neuroimaging techniques, including dopamine transporter imaging, and amyloid imaging may allow clinicians to exclude the potential misdiagnosis including Parkinsonian disorders and Alzheimer’s disease in patients with presumed idiopathic normal pressure hydrocephalus. Herein, we suggest a neuroimaging-supportive algorithm for the diagnosis of idiopathic normal pressure hydrocephalus. We suspect that this is the time to change the classical approach of diagnosing idiopathic normal pressure hydrocephalus.

Background: Mounting evidence has revealed an inverse association between cigarette smoking and the risk of Parkinson's disease (PD). Meanwhile, cigarette smoking has been found to be associated with cognitive impairment in PD patients. However, the neural mechanisms of the association between cigarette smoking and PD are not fully understood. Objective: The aim of this study is to explore the neural mechanisms of the association between cigarette smoking and PD. Methods: A total of 129 PD patients and 69 controls were recruited from the Parkinson's Progression Markers Initiative (PPMI) cohort, including 39 PD patients with regular smoking history (PD-S), 90 PD patients without regular smoking history (PD-NS), 26 healthy controls with regular smoking history (HC-S), and 43 healthy controls without regular smoking history (HC-NS). Striatal dopamine transporter (DAT) binding and gray matter (GM) volume of the whole brain were compared among the four groups. Results: PD patients showed significantly reduced striatal DAT binding compared with healthy controls, and HC-S showed significantly reduced striatal DAT binding compared with HC-NS. Moreover, smoking and PD showed a significant interaction effect in the left medial prefrontal cortex (mPFC). PD-S showed reduced GM volume in the left mPFC compared with PD-NS. Conclusion: The degeneration of dopaminergic neurons in PD results in a substantial reduction of the DAT and dopamine levels. Nicotine may act as a stimulant to inhibit the action of striatal DAT, increasing dopamine levels in the synaptic gap. The inverse alteration of dopamine levels between PD and nicotine addiction may be the reason for the inverse association between smoking and the risk of PD. In addition, the mPFC atrophy in PD-S may be associated with cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Impairments of olfactory and speech function are likely early prodromal symptoms of α‐synucleinopathy. Objective: The aim of this study is to assess whether dysprosody is present in isolated rapid eye movement sleep behavior disorder (iRBD) with hyposmia/anosmia and a normal nigrostriatal system. Methods: Pitch variability during speech was investigated in 17 iRBD subjects with normal olfactory function (iRBD‐NOF), 30 iRBD subjects with abnormal olfactory function (iRBD‐AOF), and 50 healthy controls. iRBD subjects were evaluated using the University of Pennsylvania Smell Identification Test and [123I]‐2ß‐carbomethoxy‐3ß‐(4‐iodophenyl)‐N‐(3‐fluoropropyl)‐nortropane dopamine transporter single‐photon emission computed tomography (DAT‐SPECT). All iRBD subjects completed the 24‐month follow‐up with DAT‐SPECT, speech, and olfactory testing. Results: At baseline, only iRBD‐AOF showed monopitch when compared to iRBD‐NOF (P = 0.04) and controls (P = 0.03), with no difference between iRBD‐NOF and controls (P = 1). At follow‐up, dysprosody progressed only in iRBD‐AOF with abnormal DAT‐SPECT (P = 0.03). Conclusion: Prosody is impaired in hyposmic but not in normosmic iRBD subjects before the nigrostriatal dopaminergic transmission is affected (Braak stage 2). © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Introduction: Frontotemporal lobar degeneration (FTLD) is a clinical syndrome with pathological heterogeneity, including Pick's disease and trans-activating response region (TAR) DNA-binding protein with a molecular mass of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). A previous study reported abnormal findings on dopamine transporter (DAT) imaging in 30% of patients with frontotemporal dementia (FTD) in FTLD. However, the previous study did not consider the pathological heterogeneity of FTD regarding the pathomechanism leading to abnormal DAT findings. Recently, abnormal DAT findings were reported in two patients with FTLD with motor neuron disease (MND), of which FTLD-TDP type B was the most common pathological presentation. This study investigated the DAT findings of patients with a final diagnosis of FTLD-MND to determine the frequency of occurrence of DAT abnormalities in FTLD-MND. Methods: Twenty patients with FTLD who underwent DAT single photon emission computed tomography (DAT-SPECT) were screened, and six patients with a final diagnosis of FTLD-MND were ultimately included. The patients' DAT-SPECT findings were analyzed visually and quantitatively. Neuronal loss and astrogliosis in brain regions (substantia nigra, caudate, and putamen) that could possibly affect DAT findings were evaluated in the three pathologically confirmed cases. Result: All six patients with FTLD-MND showed abnormal visual DAT-SPECT findings. In addition, in a quantitative assessment, the specific binding ratio in the striatum calculated by the Southampton method was below the lower limit of the 95% prediction interval of the healthy controls by age in all the present cases. Interestingly, three of the six patients showed abnormal findings on DAT-SPECT more than half a year before the onset of MND. Neuronal loss and astrogliosis in brain regions that may affect DAT findings were observed in three pathologically confirmed cases. Conclusion: Dopamine transporter single photon emission computed tomography revealed abnormal findings in patients with FTLD-MND, which may manifest even before the onset of MND symptoms. We believe that the possibility of future development of MND should be considered if DAT-SPECT shows abnormal findings in FTLD. [ABSTRACT FROM AUTHOR]

Introduction: Deep brain stimulation (DBS) has showed variable therapeutic effect on freezing of gait (FOG) in Parkinson's disease (PD). It is unclear which factors associated with the effect of DBS on FOG in patients with advanced PD. In this study, we investigated the correlation of pre and postoperative factors with the therapeutic effect of globus pallidus interna (GPi) DBS on FOG in PD patients.Methods: We retrospectively analyzed PD patients with FOG (N = 20) who underwent GPi DBS surgery. Postoperatively, video-based analysis for FOG severity was performed at the first DBS programming and patients were categorized into two groups according to DBS effect on FOG (11 FOG responders and 9 FOG non-responders) at medication-off state. We analyzed preoperative clinical characteristics, cognitive function, striatal dopamine transporter availability, postoperative DBS programming parameters, lead locations, and volume of tissue activated in functional subregions of GPi. Bootstrap enhanced Elastic-Net logistic regression was used to select pre and postoperative factors associated with the effect of GPi DBS.Results: Therapeutic effect of GPi DBS on FOG were correlated with the disease duration of PD before DBS surgery, preoperative improvement in FOG severity by levodopa medication, and the distance from active contact of DBS electrode to the prefrontal region of GPi anatomical site.Conclusions: Our study results suggest that the effect of GPi DBS on FOG is correlated with disease duration, levodopa responsiveness on FOG before DBS surgery and DBS electrode location, providing useful information to predict FOG outcome after GPi DBS in PD patients. [ABSTRACT FROM AUTHOR]

Background: Mounting evidence has revealed an inverse association between cigarette smoking and the risk of Parkinson’s disease (PD). Meanwhile, cigarette smoking has been found to be associated with cognitive impairment in PD patients. However, the neural mechanisms of the association between cigarette smoking and PD are not fully understood. Objective: The aim of this study is to explore the neural mechanisms of the association between cigarette smoking and PD. Methods: A total of 129 PD patients and 69 controls were recruited from the Parkinson’s Progression Markers Initiative (PPMI) cohort, including 39 PD patients with regular smoking history (PD-S), 90 PD patients without regular smoking history (PD-NS), 26 healthy controls with regular smoking history (HC-S), and 43 healthy controls without regular smoking history (HC-NS). Striatal dopamine transporter (DAT) binding and gray matter (GM) volume of the whole brain were compared among the four groups. Results: PD patients showed significantly reduced striatal DAT binding compared with healthy controls, and HC-S showed significantly reduced striatal DAT binding compared with HC-NS. Moreover, smoking and PD showed a significant interaction effect in the left medial prefrontal cortex (mPFC). PD-S showed reduced GM volume in the left mPFC compared with PD-NS. Conclusion: The degeneration of dopaminergic neurons in PD results in a substantial reduction of the DAT and dopamine levels. Nicotine may act as a stimulant to inhibit the action of striatal DAT, increasing dopamine levels in the synaptic gap. The inverse alteration of dopamine levels between PD and nicotine addiction may be the reason for the inverse association between smoking and the risk of PD. In addition, the mPFC atrophy in PD-S may be associated with cognitive impairment. [ABSTRACT FROM AUTHOR]

Abstract 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.

IntroductionFrontotemporal lobar degeneration (FTLD) is a clinical syndrome with pathological heterogeneity, including Pick’s disease and trans-activating response region (TAR) DNA-binding protein with a molecular mass of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). A previous study reported abnormal findings on dopamine transporter (DAT) imaging in 30% of patients with frontotemporal dementia (FTD) in FTLD. However, the previous study did not consider the pathological heterogeneity of FTD regarding the pathomechanism leading to abnormal DAT findings. Recently, abnormal DAT findings were reported in two patients with FTLD with motor neuron disease (MND), of which FTLD-TDP type B was the most common pathological presentation. This study investigated the DAT findings of patients with a final diagnosis of FTLD-MND to determine the frequency of occurrence of DAT abnormalities in FTLD-MND.MethodsTwenty patients with FTLD who underwent DAT single photon emission computed tomography (DAT-SPECT) were screened, and six patients with a final diagnosis of FTLD-MND were ultimately included. The patients’ DAT-SPECT findings were analyzed visually and quantitatively. Neuronal loss and astrogliosis in brain regions (substantia nigra, caudate, and putamen) that could possibly affect DAT findings were evaluated in the three pathologically confirmed cases.ResultAll six patients with FTLD-MND showed abnormal visual DAT-SPECT findings. In addition, in a quantitative assessment, the specific binding ratio in the striatum calculated by the Southampton method was below the lower limit of the 95% prediction interval of the healthy controls by age in all the present cases. Interestingly, three of the six patients showed abnormal findings on DAT-SPECT more than half a year before the onset of MND. Neuronal loss and astrogliosis in brain regions that may affect DAT findings were observed in three pathologically confirmed cases.ConclusionDopamine transporter single photon emission computed tomography revealed abnormal findings in patients with FTLD-MND, which may manifest even before the onset of MND symptoms. We believe that the possibility of future development of MND should be considered if DAT-SPECT shows abnormal findings in FTLD.

Statins are more widely used not only for the primary and secondary prevention of cardiovascular disease by blocking cholesterol biosynthesis but also for the potential neuroprotective agents during neurological disorders due to their pleiotropic effects. In this study, we investigate whether the previous use of statins affect baseline nigrostriatal dopamine loss at the time of diagnosis and longitudinal motor and cognitive outcomes in patients with Parkinson's disease. Five hundred drug-naïve patients with Parkinson's disease who underwent dopamine transporter imaging were classified into two groups according to the prior use of statins: patients with and without statin use. Multivariate linear regression was used to determine intergroup differences in dopamine transporter availability. We evaluated the longitudinal changes in levodopa-equivalent dose and dementia conversion between the groups using a linear mixed model and survival analysis, respectively. In addition, mediation analysis was applied to examine the effect of total cholesterol. Patients with Parkinson's disease treated with statins had a lower baseline dopamine transporter availability in the anterior (2.13 ± 0.55 versus 2.37 ± 0.67; P = 0.002), posterior (1.31 ± 0.43 versus 1.49 ± 0.54; P = 0.003) and ventral putamina (1.40 ± 0.39 versus 1.56 ± 0.47; P = 0.002) than that in matched patients with Parkinson's disease without statins. After adjusting for age at symptom onset, sex, disease duration and vascular risk factors, linear regression models showed that a previous treatment with statins remained significantly and independently associated with more severely decreased dopamine transporter availability in the anterior putamen (Beta = -0.140, P = 0.004), posterior putamen (Beta = -0.162, P = 0.001) and ventral putamen (Beta = -0.140, P = 0.004). A linear mixed model revealed that patients with Parkinson's disease being treated with statins had a faster longitudinal increase in levodopa-equivalent dose than those without. A survival analysis showed that the rate of dementia conversion was significantly higher in patients with Parkinson's disease with statins (hazard ratio, 2.019; 95% confidence interval, 1.108-3.678; P = 0.022) than those without. Mediation analyses revealed that the effect of statin treatment on baseline dopamine transporter availability and longitudinal outcome was not mediated by total cholesterol levels. This study suggests that statin use may have a detrimental effect on baseline nigrostriatal dopamine degeneration and long-term outcomes in patients with Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Freezing of gait (FOG) is a common symptom in Parkinson's Disease (PD) patients. Previous studies have reported relationships between FOG, substantia nigra (SN) degeneration, dopamine transporter (DAT) concentration, as well as amyloid β deposition. However, there is a paucity of research on the concurrent impact of white matter damage.Objectives: To assess the inter-relationships between these different co-morbidities, their impact on future FOG and whether they act independently of each other.Methods: We used baseline MRI and longitudinal gait data from 423 de novo PD patients from the Parkinson's Progression Markers Initiative (PPMI). We used deformation based morphometry (DBM) from T1-weighted MRI to measure SN atrophy, and segmentation of white matter hyperintensities (WMH) as a measure of WM pathological load. Putamen and caudate DAT levels from SPECT as well as cerebrospinal fluid (CSF) amyloid β were obtained directly from the PPMI. Following correlation analyses, we investigated whether WMH burden mediates the impact of amyloid β on future FOG.Results: SN DBM, WMH load, putamen and caudate DAT activity and CSF amyloid β levels were significantly different between PD patients with and without future FOG (p < 0.008). Mediation analysis demonstrated an effect of CSF amyloid β levels on future FOG via WMH load, independent of SN atrophy and striatal DAT activity levels.Conclusions: Amyloid β might impact future FOG in PD patients through an increase in WMH burden, in a pathway independent of Lewy body pathology. [ABSTRACT FROM AUTHOR]

Acquired hepatocerebral degeneration, levodopa responsive parkinsonism, dopamine transporter imaging, neuromelanin-sensitive imaging, primary biliary cholangitis Keywords: acquired hepatocerebral degeneration; levodopa responsive parkinsonism; dopamine transporter imaging; neuromelanin-sensitive imaging; primary biliary cholangitis EN acquired hepatocerebral degeneration levodopa responsive parkinsonism dopamine transporter imaging neuromelanin-sensitive imaging primary biliary cholangitis 464 468 5 04/03/21 20210401 NES 210401 Acquired hepatocerebral degeneration (AHD) is a syndrome that causes progressive cognitive decline, psychiatric symptoms, movement disorders, and myelopathy in approximately 1% of chronic hepatic dysfunction cases. DAT studies and levodopa responsiveness were not present in normal DAT uptake cases.5 Table 1 shows the clinical and imaging features of previous AHD with parkinsonism cases with decreased DAT uptake, including our case. [Extracted from the article]

Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used hypoglycaemic agents and improve glucose metabolism by enhancing the bioavailability of active glucagon-like peptide-1. In this study, we hypothesized that treatment with DPP4 inhibitors may have beneficial effects on nigrostriatal dopamine and longitudinal motor performance in diabetic patients with Parkinson's disease. We classified 697 drug naive patients with de novo Parkinson's disease who had undergone dopamine transporter imaging into three groups according to a prior diagnosis of diabetes and use of DPP4 inhibitors: diabetic patients with Parkinson's disease being treated with (n = 54) or without DPP4 inhibitors (n = 85), and non-diabetic patients with Parkinson's disease (n = 558). Diabetic patients with Parkinson's disease being treated with DPP4 inhibitors had a higher baseline dopamine transporter availability in the anterior (2.56 ± 0.74 versus 2.10 ± 0.50; P = 0.016), posterior (1.83 ± 0.69 versus 1.40 ± 0.50; P < 0.001), and ventral putamina (1.72 ± 0.58 versus 1.35 ± 0.37; P = 0.001) than that in diabetic patients with Parkinson's disease without DPP4 inhibitors. Additionally, diabetic patients with Parkinson's disease being treated with DPP4 inhibitors had higher dopamine transporter availability in the posterior putamen than that in non-diabetic patients with Parkinson's disease (1.83 ± 0.69 versus 1.43 ± 0.59; P < 0.001). After adjusting for age, sex, disease duration, and vascular risk factors, linear regression models showed that a prior treatment of DPP4 inhibitors remained independently and significantly associated with dopamine transporter availability in the anterior (β = -0.186, P = 0.012; β = -0.207, P = 0.003), posterior (β = -0.336, P < 0.001; β = -0.286, P < 0.001), and ventral putamina (β = -0.204, P = 0.005; β = -0.250, P < 0.001). A linear mixed model revealed that the diabetic group with Parkinson's disease being treated with DPP4 inhibitors had a slower longitudinal increase in levodopa-equivalent dose than the other groups (P = 0.003). Survival analyses showed that the rate of levodopa-induced dyskinesia was significantly lower in the diabetic group with a prior treatment with DPP4 inhibitors than the diabetic group without DPP4 inhibitors (hazard ratio = 0.194, P = 0.037). These findings suggest that DPP4 inhibitors may confer beneficial effects on the baseline nigrostriatal dopamine degeneration and long-term motor outcomes in diabetic patients with Parkinson's disease and may extend its role into non-diabetic patients with Parkinson's disease. [ABSTRACT FROM AUTHOR]

Purpose: The precise quantification of dopamine transporter (DAT) density on N-(3-[18F]Fluoropropyl)-2β-carbomethoxy-3β-(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. [ABSTRACT FROM AUTHOR]

Background: The imbalance between the production and clearance of alpha-synuclein and its consequent accumulation plays a pivotal role in the pathogenesis of Parkinson’s disease (PD). The diminished clearance of alpha-synuclein may be partly attributable to impaired interstitial fluid, which can be reflected by the extent of dilated perivascular space (dPVS). We studied the association between dPVS and dopamine neuronal degeneration.Method: We screened 71 healthy controls (HCs) and 88 patients from the Parkinson Progression Markers Initiative (PPMI) database. The dPVS was evaluated in different brain regions on axial T2-weighted images, and dopamine transporter (DAT) imaging data was used to elucidate the extent of dopaminergic neuronal degeneration. Patients with PD were further divided into two groups (SN + PD and SN − PD groups) according to whether dPVS was observed in the substantia nigra (SN). DAT uptake values and clinical scales were compared between the patients with PD and HCs and against dPVS scores. We also investigated the correlation between baseline dPVS scores and longitudinal DAT changes.Results: Relative to the HCs, patients with PD had more dPVS in the SN and basal ganglia (BG). PD patients with dPVS in the SN region exhibited greater expression of tau protein in cerebrospinal fluid (P = 0.038) and a trend towards decreased DAT binding (P = 0.086) relative to those without SN dPVS. No correlations were found between dPVS scores and DAT uptake values or between dPVS scores and longitudinal DAT changes.Conclusion: The dPVS in the SN of patients with PD may reflect the degeneration of dopaminergic neurons.

Lewy body dementia (LBD) consists of two dementia syndromes associated with Lewy body pathology: Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB). The common pathological basis in the nervous systems supports considerable clinical overlap between them. Dysautonomia, olfactory dysfunction, rapid eye movement sleep behavior disorder (RBD), and psychiatric symptoms are frequently seen in the course of both disorders during the prodromal stage. Although the defining feature of PDD is that dementia develops in the setting of well‐established Parkinson's disease, the presence of parkinsonism is not essential for the clinical diagnosis of DLB. It is accepted that nigrostriatal dopaminergic degeneration is a key pathophysiology in the development of parkinsonism, but the time course of nigral degeneration in LBD remains unclear. In both disorders, cortical Lewy bodies (LBs) and Lewy neurites are often widespread and correlate with the severity of the dementia. The progression pattern of Lewy body pathology in LBD remains unestablished, but the cortical involvement of incidental LBs in individuals without parkinsonism suggests the presymptomatic neuropathological precursor for DLB rather than PDD. Many studies have revealed that cerebral β‐amyloid accumulation is related to the timing of the onset of dementia relative to that of parkinsonism in LBD. Therefore, we focused on the time courses of nigral degeneration and cerebral β‐amyloid accumulation during the disease progression in LBD. Recent neuroimaging and cerebral spinal fluid findings have provided opportunities for understanding the antemortem neuropathological changes, and LBD‐associated findings were also reviewed in this article. [ABSTRACT FROM AUTHOR]

Background and Objectives: The PARS (Parkinson Associated Risk Syndrome) study was designed to test whether screening for hyposmia followed by dopamine transporter imaging can identify risk for conversion to clinical PD, and to evaluate progression markers during the prodromal period.Methods: Subjects with hyposmia completed annual clinical evaluations and biennial [123 I]ß-CIT single-photon emission computed tomography scans. Subjects were categorized as normal (>80% age-expected tracer uptake; n = 134), indeterminate (>65-80%; n = 30), and dopamine transporter deficit (≤65%; n = 21) by their baseline scan, and survival analysis was used to compare risk of conversion to motor PD. Progressing to a scan with a dopamine transporter deficit was assessed for those subjects with either normal or indeterminate baseline imaging.Results: Over a mean of 6.3 [standard deviation: 2.2] years of follow-up, 67% (n = 14) of dopamine transporter deficit subjects, 20% (n = 6) of dopamine transporter indeterminate subjects, and 4% (n = 6) of dopamine transporter normal subjects converted to a PD diagnosis (P < 0.0001). Among subjects without dopamine transporter deficit at baseline, a reduction to ≤65% age-expected uptake occurred in 12 of 30 (40%) with indeterminate dopamine transporter and 7 of 134 (5%) with no dopamine transporter DAT deficit (P < 0.0001). Imaging conversion during follow-up was associated with subsequent clinical conversion (hazard ratio: 9.6; P = 0.0157).Discussion and Conclusions: Long-term follow-up of the PARS cohort demonstrated a high rate of conversion to clinical PD in subjects who either had abnormal dopamine transporter imaging at baseline or developed abnormal imaging during follow-up. These data extend the earlier PARS findings and present new results showing the sequence of incident imaging deficit, imaging progression, and clinical changes that occur in prodromal PD. © 2020 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Gait automaticity, which is impaired in patients with Parkinson's disease (PD), can be quantified by gait variability analysis. Among the 3 regions of the striatum (sensorimotor, executive, and limbic), the sensorimotor region may play a crucial role in motor automaticity in healthy individuals. However, neural correlates of impaired gait automaticity are poorly investigated in PD.Objective: We aimed to examine the relationship between gait automaticity and striatal dopaminergic depletion in drug-naïve PD patients.Methods: A total of 21 drug-naïve PD patients and 12 healthy controls were enrolled. Gait parameters were measured via wearable inertial sensors under fast-paced gait or cognitive dual-task conditions, and their respective coefficient of variation (CV) and dual-task cost were calculated. The extent of striatal dopaminergic depletion was evaluated by dopamine transporter (DAT) imaging with single-photon emission computed tomography using N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-[123 I]iodophenyl)nortropane. Correlation between DAT uptake and gait variables was analyzed using the region-of-interest analysis for the 3 right or left striatal regions and voxel-based analysis.Results: PD had higher mean bilateral CV and dual-task cost of stride length than healthy controls. The mean bilateral CV of stride length was negatively correlated with DAT uptake in the bilateral executive regions of the striatum. Voxel-based analysis revealed a negative correlation between the mean bilateral CV of stride length and DAT uptake in the anteromedial striatum.Conclusions: Dopaminergic denervation in the anteromedial striatum, a part of the executive region, is associated with impaired gait automaticity in drug-naïve PD patients. This region may compensate for the posterior sensorimotor striatum, maintaining gait automaticity. © 2020 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: The imbalance between the production and clearance of alpha-synuclein and its consequent accumulation plays a pivotal role in the pathogenesis of Parkinson's disease (PD). The diminished clearance of alpha-synuclein may be partly attributable to impaired interstitial fluid, which can be reflected by the extent of dilated perivascular space (dPVS). We studied the association between dPVS and dopamine neuronal degeneration. Method: We screened 71 healthy controls (HCs) and 88 patients from the Parkinson Progression Markers Initiative (PPMI) database. The dPVS was evaluated in different brain regions on axial T2-weighted images, and dopamine transporter (DAT) imaging data was used to elucidate the extent of dopaminergic neuronal degeneration. Patients with PD were further divided into two groups (SN + PD and SN − PD groups) according to whether dPVS was observed in the substantia nigra (SN). DAT uptake values and clinical scales were compared between the patients with PD and HCs and against dPVS scores. We also investigated the correlation between baseline dPVS scores and longitudinal DAT changes. Results: Relative to the HCs, patients with PD had more dPVS in the SN and basal ganglia (BG). PD patients with dPVS in the SN region exhibited greater expression of tau protein in cerebrospinal fluid (P = 0.038) and a trend towards decreased DAT binding (P = 0.086) relative to those without SN dPVS. No correlations were found between dPVS scores and DAT uptake values or between dPVS scores and longitudinal DAT changes. Conclusion: The dPVS in the SN of patients with PD may reflect the degeneration of dopaminergic neurons. [ABSTRACT FROM AUTHOR]

Objectives: Hyperechogenicity of the substantia nigra (SN) and abnormal dopamine transporter-single-photon emission computed tomography (DAT-SPECT) are biomarkers commonly used in the assessment of prodromal synucleinopathy. Our goals were as follows: (1) to compare echogenicity of SN in idiopathic rapid eye movement (REM) behavior disorder (iRBD), Parkinson's disease (PD) without RBD (PD-noRBD), PD with RBD (PD + RBD), and control subjects; and (2) to examine association between SN degeneration assessed by DAT-SPECT and SN echogenicity.Patients/methods: A total of 61 subjects with confirmed iRBD were examined using Movement Disorders Society-unified PD rating scale (MDS-UPDRS), TCS (transcranial sonography) and DAT-SPECT. The results were compared with 44 patients with PD (25% PD + RBD) and with 120 age-matched healthy subjects.Results and Conclusion: The abnormal SN area was found in 75.5% PD, 23% iRBD and 7.3% controls. Median SN echogenicity area in PD (0.27 ± 0.22 cm2) was higher compared to iRBD (0.07 ± 0.07 cm2; p < 0.0001) and controls (0.05 ± 0.03 cm2; p < 0.0001). SN echogenicity in PD + RBD was not significantly different from PD-noRBD (0.30 vs. 0.22, p = 0.15). Abnormal DAT-SPECT was found in 16 iRBD (25.4%) and 44 PD subjects (100%). No correlation between the larger SN area and corresponding putaminal binding index was found in iRBD (r = -0.13, p = 0.29), nor in PD (r = -0.19, p = 0.22). The results of our study showed that: (1) SN echogenicity area in iRBD was higher compared to controls, but the hyperechogenicity was present only in a minority of iRBD patients; (2) SN echogenicity and DAT-SPECT binding index did not correlate in either group; and (3) SN echogenicity does not differ between PD with/without RBD. [ABSTRACT FROM AUTHOR]

Racial and ethnic disparities in the prevalence of neurodegenerative diseases exist. This study examined the agreement between gold standard diagnosis and visual assessment of dopamine transporter (DaT) imaging in Hispanic and non-Hispanic patients being evaluated for Parkinsonian syndromes (PS). Methods: A retrospective review of DaT imaging and demographic data was performed with institutional review board approval. Documented interpretation by visual assessment was used to classify scans as normal or abnormal. The gold standard for the final diagnosis of PS was determined by a neurologist after 2 or more years of clinical follow-up. Data were analyzed with a z-test for uncorrelated samples. Results: In 30 Hispanic patients, DaT imaging was abnormal in 17, normal in 12, and nondiagnostic in 1. Of those with abnormal imaging, PS was confirmed in 16 of 17. Of those with normal imaging, no PS was confirmed in any patient. Sensitivity was 100%, and specificity was 92%. The single patient with nondiagnostic imaging was excluded. Of 77 non-Hispanic patients, visual assessment of DaT imaging was abnormal in 51. Of those with abnormal imaging, PS was confirmed in 48 of 51. Of those with normal imaging, no PS was confirmed in 22 of 26. Sensitivity was 92%, and specificity was 88%. There was no statistically significant difference (z = 0.34) in the rates of agreement between the gold standard and DaT imaging in Hispanic versus non-Hispanic patients. The study sample size afforded a power of 0.60. Conclusion: No significant difference was found in the accuracy of DaT imaging between Hispanic and non-Hispanic patients. Accuracy was high for both groups. [ABSTRACT FROM AUTHOR]

Introduction: Glucocerebrosidase gene (GBA) variants are associated with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The molecular mechanisms underlying these diseases with GBA variants, however, are not well understood. In order to determine the effect of a deletion mutation in GBA, we performed a neuroimaging, genetic, and enzymatic study in a Japanese family with a gross deletion of exons 3 to 11 in GBA.Methods: We performed [123I] FP-CIT SPECT and [123I] N-isopropyl-p-iodoamphetamine SPECT (IMP-SPECT), and determined GBA expression and glucocerebrosidase (GCase) activity in leukocytes in two GBA-associated PD patients and nine unaffected individuals (including four mutation carriers) in a Japanese family with a heterozygous gross deletion mutation in the GBA gene.Results: The two PD patients and two of the four clinically unaffected carriers showed decreased [123I] FP-CIT uptake. IMP-SPECT showed a pattern like that in DLB in one patient. When we compared PD patients with GBA mutations with clinically unaffected carriers, there was a poor correlation between the development of PD and the expression level of GBA or GCase activity.Conclusion: We confirmed the gross deletion mutation in the GBA gene, which appeared to be associated with the PD or reduced [123I] FP-CIT in this family. However, since we cannot conclude whether a reduction of GCase activity is directly correlated with the pathogenesis of PD or not, longitudinal follow-up of this family is needed. [ABSTRACT FROM AUTHOR]

Background: Neuromelanin magnetic resonance imaging (NmMRI) and 123I-FP-CIT dopamine transporter single photon emission computed tomography (DAT-SPECT) provide specific information that distinguishes Parkinson's disease (PD) from non-degenerative parkinsonian syndrome (NDPS).Purpose: To determine whether a multiparametric scoring system (MSS) could improve accuracy compared to each parameter of DAT-SPECT and NmMRI in differentiating PD from NDPS.Material and Methods: A total of 49 patients, including 14 with NDPS, 30 with PD, and five with atypical parkinsonian disorder (APD) underwent both NmMRI and DAT-SPECT and were evaluated. The average (Ave) and the asymmetry index (AI) were calculated in the substantia nigra compacta area (SNc-area), SNc midbrain-tegmentum contrast ratio (SNc-CR), and specific binding ratio (SBR). Cut-off values were determined, using receiver operating characteristic (ROC) analysis, for the differentiation of PD from NDPS on the statistically significant parameters. All cases were scored as either 1 (PD) or 0 (NDPS) for each parameter according to its threshold. These individual scores were totaled for each case, yielding a combined score for each case to obtain a cut-off value for the MSS.Results: The Ave-SNc-area, Ave-SNc-CR, and Ave-SBR in PD were significantly lower than those in NDPS. The AI-SNc-area and AI-SBR in PD were significantly higher than those in NDPS. Of the five parameters, the highest accuracy was 93% for the Ave-SNc-area. For the MSS, a cut-off value of 3 was the accuracy of 96%. Besides, no significant difference was observed between PD and APD on all parameters.Conclusion: An MSS has comparable or better accuracy compared to each parameter of DAT-SPECT and NmMRI in distinguishing PD from NDPS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Only 25% to 56% of patients with CBD pathology are correctly diagnosed antemortem.1 Further, in one autopsy study, only 7 of 13 patients presenting with CBS had CBD at postmortem.2 One imaging modality used for diagnosis is dopamine transporter (DaT) imaging, which usually demonstrate loss of dopaminergic innervation to the striatum, occasionally with severe lateralization.3 Here, we present a case with probable CBD who had received a DaT-single-photon emission computed tomography (SPECT) 9 years before diagnosis, as part of establishing a normal DaT-SPECT reference data set. Keywords: corticobasal degeneration; dopamine transporter imaging; atypical parkinsonism EN corticobasal degeneration dopamine transporter imaging atypical parkinsonism 607 609 3 05/04/21 20210501 NES 210501 Little is known about the early stages of corticobasal degeneration (CBD), which presents itself in a variety of syndromes of which the most common presentation is referred to as corticobasal syndrome (CBS). During analysis of the DaT-SPECT, the patient was identified as 1 of the healthy controls who had volunteered to serve as normal reference material 9 years earlier (Fig. [Extracted from the article]

Objective: Impulse control behaviors (ICBs) frequently coexist with Parkinson's disease (PD). However, the predictors of ICBs in PD remain unclear, and there is limited data on the biological correlates of ICBs in PD. In this study, we examined clinical, imaging, and biological variables to identify factors associated with longitudinal changes in ICBs in early-stage PD., Methods: The data for this study were obtained from the Parkinson's Progression Markers Initiative, an international prospective cohort study that evaluates markers of disease progression in PD. We examined clinical, imaging, and biological variables to determine their associations with ICBs over a period of up to 5 years. Cox regression models were employed to investigate the predictors of ICBs in early-stage, untreated PD., Results: The study enrolled 401 individuals with PD and 185 healthy controls (HC). At baseline, 83 PD subjects (20.7%) and 36 HC (19.5%) exhibited ICBs. Over the course of 5 years, the prevalence of ICBs increased in PD (from 20.7% to 27.3%, p < 0.001), while it decreased in HC (from 19.5% to 15.2%, p < 0.001). Longitudinally, the presence of ICBs in PD was associated with depression, anxiety, autonomic dysfunction, and excessive daytime sleepiness (EDS). However, there was no significant association observed with cognitive dysfunction or motor severity. Treatment with dopamine agonists was linked to ICBs at years 3 and 4. Conversely, there was no association found between ICBs and presynaptic dopaminergic dysfunction. Additionally, biofluid markers in baseline and the first year did not show a significant association with ICBs. A predictive index for ICBs was generated, incorporating three baseline characteristics: anxiety, rapid eye movement sleep behavior disorder (RBD), and p-tau levels in cerebrospinal fluid (CSF)., Conclusion: During the early stages of PD, there is a notable increase in ICBs over time. These ICBs are associated with depression, anxiety, autonomic dysfunction, EDS, and the use of dopaminergic medications, particularly dopamine agonists. Anxiety, RBD, and p-tau levels in CSF are identified as predictors for the incident development of ICBs in early PD. Further longitudinal analyses will provide a more comprehensive understanding of the associations between ICBs and imaging findings, as well as biomarkers. These analyses will help to better characterize the relationships and implications of these factors in the context of ICBs in early PD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Gan, Wu, Wan, Song, Liu and Zhang.)

Aim: Rapid eye movement sleep behavior disorder (RBD) and psychiatric symptoms often antedate the clinical diagnosis of Parkinson's disease or dementia with Lewy bodies. The purpose of this study was to investigate RBD and its relevance to Lewy body disease (LBD) in patients with late‐onset psychiatric disorders. Methods: Study subjects included 19 patients with late‐onset psychiatric disorders who exhibited REM sleep without atonia (RWA), which is a hallmark of RBD on polysomnography, at our psychiatric ward. Clinical profiles and radiological findings by cardiac [123I]‐metaiodobenzylguanidine ([123I]‐MIBG) scintigraphy and imaging for the dopamine transporter (DAT) were compared between patients with and without RBD symptoms. The correlations between the percentage of RWA in the total rapid eye movement sleep (%RWA) and radiological findings were also investigated. Results: Nine patients reported RBD symptoms only on specific questioning, but clinical profiles, including the prevalence of antipsychotropic usage, did not differ when compared to the remaining 10 patients without RBD (incidental RWA group). The median %RWA was significantly higher in the definite RBD group than in the incidental RWA group. Although the cardiac [123I]‐MIBG uptake was significantly lower in the definite RBD group than in the incidental RWA group, there was overlap in the specific binding ratio on DAT scan. Conclusion: The severity of %RWA was highly correlated with the value of cardiac [123I]‐MIBG uptake, but not with specific binding ratio on DAT scan. Clinical history of RBD and cardiac [123I]‐MIBG scintigraphy are helpful for an early differential diagnosis of LBD from late‐onset psychiatric disorders, even before parkinsonism or dementia appears. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present study was to determine the relation of urinary dysfunction with motor symptoms and nigrostriatal neuron loss in drug-naïve patients with Parkinson's disease (PD). We therefore examined the relation of overactive bladder (OAB) symptoms with motor symptoms and striatal dopamine transporter (DAT) binding measured by [123-Iodine]-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenylnortropane) dopamine transporter single-photon emission computed tomography (123I-FP-CIT SPECT).Patients and Methods: Thirty-one untreated PD patients (12 men and 19 women with a mean age of 71.2 ± 6.7 years) were included in this study. Patients were evaluated with overactive bladder symptom score (OABSS) and divided into an OAB group and Non-OAB group. They underwent clinical assessments and 123I-FP-CIT SPECT imaging. Motor symptoms were assessed using Unified Parkinson's Disease Rating Scale (UPDRS).Results: The results showed that UPDRS motor score (p = 0.01) and akinetic-rigid score (p = 0.002) were higher and that striatal DAT availability (p = 0.01) was lower in the OAB group than in the Non-OAB group. However, tremor score, age, and duration of PD showed no significant differences between the OAB group and Non-OAB group.Conclusions: Urinary dysfunction in untreated PD is related with increase in motor symptoms (especially bradykinesia and axial symptoms) and reduction of striatal DAT availability. [ABSTRACT FROM AUTHOR]

Imaging studies are necessary prior to subthalamic deep brain stimulation (STN-DBS). Dopamine transporter (DAT) imaging is a powerful tool for visualizing dopamine terminals in the striatum, but its usefulness in STN-DBS is unclear. Here, we retrospectively investigated the relationship between motor symptoms and the specific binding ratio (SBR) on DAT imaging in patients with Parkinson's disease (PD). We included 23 consecutive patients (9 female; 14 male) who were evaluated for DBS eligibility between October 2013 and October 2014 and subsequently received bilateral STN-DBS. Correlation and simple regression analyses were performed on SBR values and clinical parameters before and after surgery. SBR value was negatively correlated with Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the “ON” state before surgery (r s = − 0.637, p = 0.001) and positively correlated with the reduction of the levodopa equivalent daily dose by surgery (r = 0.422, p = 0.045). A simple regression analysis revealed that SBR value was positively correlated with UPDRS motor score improvement after levodopa challenge before surgery (p = 0.001, R 2 = 0.423). DAT imaging may be useful in STN-DBS candidate selection and the identification of the therapeutic mechanism of STN-DBS in patients with advanced PD and motor symptom fluctuations. [ABSTRACT FROM AUTHOR]