進行性核上性麻痺

INTRODUCTION: Orthostatic hypotension (OH) commonly impairs the quality of life and prognosis of patients with neurodegenerative disorders. Since skeletal muscle functions as a peripheral pump for blood pressure stabilization and a reservoir for intracellular water, we investigated its association with body composition in these patients. METHODS: This prospective cross-sectional study included 86 patients with neurodegenerative disorders from Parkinsonism-related Multidisciplinary Clinic in Peking Union Medical College Hospital (PUMCH), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and other atypical parkinsonian syndromes (APS). OH was defined as a sustained reduction in systolic blood pressure of ≥20 mmHg or diastolic blood pressure of ≥10 mmHg within 3 min of active standing. Participants were divided into with OH and without OH (non-OH). Body composition was measured via Bioelectrical Impedance Analysis (BIA). The measured values were normalized to height squared to generating indices such as the fat-free mass index (FFMI) and appendicular muscle mass index (AMI). Clinical scores, levodopa equivalent daily dosage (LEDD), and grip strength were compared between groups. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 (AWGS2019) criteria. RESULTS: The incidence of OH was 45.3%, significantly higher in MSA (58.0%) than in PSP (13.3%). Sarcopenia prevalence did not differ significantly between groups. Elastic net and support vector machine (SVM) analysis identified lower limb extracellular water index (LLEWI) and AMI as the most predictive body composition indicators for OH. Linear regression confirmed AMI as an independent negative predictor of orthostatic systolic blood pressure change (β = -4.69, p = 0.008). CONCLUSION: Our findings indicate that OH is significantly associated with decreased AMI and lower LLEWI. Measuring these indices may offer valuable insights into OH risk, potentially serving as a more sensitive early indicator than a formal diagnosis of sarcopenia.

BACKGROUND: Progressive supranuclear palsy (PSP) is a tauopathy for which there is limited understanding of epidemiological risk factors. OBJECTIVE: The objective of this study was to identify premorbid nonmedical and medical risk factors for PSP diagnosis in a large prospective population-based cohort. METHODS: We performed a matched nested case-control study using the UK Biobank (UKB) cohort consisting of >500,000 adults aged 37 to 73 years. PSP diagnoses were identified from 2007 to censor date (August 2025) and matched 1:10 by age and sex to control subjects without parkinsonism or dementia diagnoses. We derived risk factors using an iterative logistic regression approach. RESULTS: There were 240 incident PSP diagnoses in the UKB. In the fully adjusted model, premorbid depression (odds ratio [OR], 3.22; 95% confidence interval [CI], 2.30-4.50; P < 0.001), delirium (OR, 6.76; 95% CI, 4.08-11.19; P < 0.001), and functional gastrointestinal disorders (OR, 1.91; 95% CI, 1.39-2.63; P < 0.001) were associated with increased risk. Heavy alcohol consumption was associated with higher risk compared with moderate consumption (OR, 1.65; 95% CI: 1.21-2.26; P = 0.0017). Body mass index (BMI) and alcohol consumption had nonlinear risk profiles. Cancer diagnosis was inversely associated with PSP (OR, 0.56; 95% CI, 0.40-0.79; P < 0.001). Depression and delirium diagnoses remained significant 5 to 10 years before diagnosis. CONCLUSIONS: In this large prospective cohort, PSP was associated with premorbid lifestyle practices and neuropsychiatric diagnoses years before diagnosis. This suggests a long premotor phase and highlights opportunities for earlier diagnosis and further mechanistic investigation. The inverse association with cancer mirrors the relationship seen in other neurodegenerative conditions and may point toward shared mechanisms. © 2026 International Parkinson and Movement Disorder Society.

BACKGROUND: Progressive supranuclear palsy (PSP) is characterized not only by motor and oculomotor deficits, but also significant cognitive and behavioural impairments. The Short Cognitive and Neuropsychiatric Assessment Scale (ShoCo) was recently published and appears to be an efficient instrument to evaluate these deficits. However, feasibility testing and validation in real-world cohorts are needed. METHODS: In this cross-sectional study, the ShoCo was administered in 304 consecutively recruited multi-ethnic Malaysian patients (75 PSP, and for comparison Parkinson's disease patients with dementia [PDD; n = 53] and without dementia [PDND; n = 176]). Clinico-demographic features including disease severity (PSP Clinical Deficits Scale [PSP-CDS] and Cortical Basal ganglia Functional Scale [CBFS]) and Montreal Cognitive Assessment (MoCA), were collected. A subset of PSP patients (n = 16) also underwent a comprehensive neuropsychological battery by a neuropsychologist blinded to the ShoCo results. RESULTS: Highly significant differences were found between PSP and PDD vs. PDND for the ShoCo total and all subdomain scores (all P < 0.001). PSP showed greater disinhibition, whereas PDD had more severe bradyphrenia, apathy and dysexecution. In PSP patients, the ShoCo correlated significantly and moderately with the PSP-CDS (rs = 0.39), CBFS (rs = 0.39), and MoCA (rs = -0.46). There were also significant and strong correlations between the ShoCo and neuropsychological tests of executive function and attention/processing speed (rs∼0.5-0.6). CONCLUSIONS: The ShoCo is a practical cognitive-behavioural screening tool that quantifies clinically relevant deficits in PSP. It enables the inclusion of severely affected patients in clinical and research settings and may reduce missing data while enhancing the representativeness of phenotypic datasets.

BACKGROUND: Progressive supranuclear palsy (PSP) is both an underdiagnosed and a frequently misdiagnosed disorder. To remedy these diagnostic limitations, MRI has been used to investigate brain morphology to differentiate PSP from Parkinson's disease (PD) and multiple system atrophy (MSA). However, while nigrostriatal degeneration and tau aggregation are prominent in PSP, and result in iron accumulation and atrophy in the region, substantia nigra (SN) atrophy remains an underexplored diagnostic marker. PURPOSE: To investigate the diagnostic utility of QSM-derived SN parameters for PSP. STUDY TYPE: Retrospective. POPULATION: 123 (59 Males/64 Females) PD patients, 48 (26 M/22 F) MSA patients, and 22 (11 M/11 F) PSP patients were included in the main dataset. MSA patients include 20 parkinsonian type (MSA-P) (11 M/9 F) and 18 cerebellar type (MSA-C) (9 M/9 F) of MSA with 10 undetermined subtype. The external validation set included 12 (6 M/6 F) healthy controls, 13 PD (7 M/6 F), and 10 PSP (6 M/4 F) patients. FIELD STRENGTH AND SEQUENCE: 3 T, MPRAGE T1-weighted imaging and multi-echo gradient echo imaging (mGRE) for QSM. ASSESSMENT: Group level differences of SN volume, magnetic susceptibility, and susceptibility-to-volume ratio (SVR) among PSP, PD, and MSA groups, and these metrics' differentiating power are measured. Bivariate logistic regression with T1-based morphological markers alongside SN metrics is performed. STATISTICAL TESTS: Mann-Whitney U test for group comparisons. Receiver operating characteristic analysis with bootstrapping. p < 0.05 after Bonferroni correction is defined as statistically significant result. RESULTS: The SN SVR was significantly higher in the PSP group compared to the MSA group and the MSA-P group. Moreover, using pons measurements with SN SVR in a bivariate model resulted in the highest differentiation between the PSP and MSA groups (AUC = 0.88, 95% CI: [0.78-0.95]), particularly driven by the increased differentiation between the PSP and MSA-P groups (AUC = 0.88, 95% CI: [0.75-0.98]). External validation supported the generalizability of SN SVR, yielding 100% sensitivity and 80% specificity for differentiating PSP from HC and PD. DATA CONCLUSION: QSM-based SN morphometry can complement T1-weighted imaging for Parkinsonism assessment. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

BACKGROUND: Behavioral variant of frontotemporal dementia (bvFTD) often presents with parkinsonism. Our study aimed to characterize the dopaminergic deficit pattern in bvFTD-parkinsonism (bvFTD-P) using dopamine transporter (DAT) positron emission tomography (PET) and to assess its potential value in differentiating bvFTD-P from progressive supranuclear palsy (PSP), multiple system atrophy-parkinsonism (MSA-P), and Parkinson disease (PD). METHODS: A total of 30 bvFTD-P patients underwent 11C-CFT or 18F-FP-CIT PET and were compared with 71 patients with PSP, 41 with MSA-P, 61 with PD, and 43 healthy controls (HC). DAT binding values in the caudate, anterior putamen, and posterior putamen, as well as caudate/anterior putamen (C/AP) and caudate/posterior putamen (C/PP) ratios, were analyzed with generalized linear models. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic accuracy of DAT binding values and ratios. RESULTS: BvFTD-P patients exhibited significantly reduced DAT binding in the caudate, anterior putamen, and posterior putamen compared with HC (all P<0.01), with a caudate-predominant deficit pattern (lower C/AP and C/PP ratios), contrasting with the putamen-predominant loss observed in PSP, MSA-P, and PD. This caudate-predominant pattern was replicated in the independent 18F-FP-CIT cohort. ROC analysis demonstrated that the C/PP ratio provided superior discriminatory performance between bvFTD-P and HC or other parkinsonian syndromes than absolute binding values. Furthermore, lateralization of striatal DAT reduction corresponded to the side of predominant motor symptoms. CONCLUSIONS: The caudate-predominant pattern of striatal dopaminergic deficit in bvFTD-P may serve as a useful imaging biomarker for differentiating it from PSP, MSA-P, and PD.