Introduction: Brain-derived neurotrophic factor (BDNF) plays an important role in the survival of dopaminergic neurons. Clinical studies have suggested that serum BDNF levels are reduced in patients with Parkinson's disease (PD). However, no study has investigated peripheral BDNF levels and BDNF Val66Met polymorphism in the prodromal stage of PD and their relationship with disease conversion. Methods: In total, 120 patients with video-polysomnography confirmed isolated REM sleep behavior disorder (iRBD) and 120 healthy controls (HCs) were enrolled. Genetic analyses were performed, and plasma levels of BDNF were measured. All patients with iRBD underwent comprehensive clinical testing, and 107 iRBD patients were prospectively followed up. Results: Plasma BDNF levels were significantly lower in the iRBD group than in HCs (18,878.85 pg/mL vs. 24,649.85 pg/mL, p = 0.002), but no differences were observed in BDNF Val66Met carrier rates between the two groups. Plasma BDNF levels did not differ significantly between BDNF Val66Met carriers and noncarriers. Notably, higher plasma BDNF levels were associated with an increased risk of short-term disease conversion (hazard ratio = 3.418, 95% CI: 1.520-7.684, p = 0.003), whereas BDNF Val66Met carrier rates showed no such association. Conclusion: Our findings suggest that plasma BDNF is significantly associated with iRBD and may likely serve as a prognostic biomarker for the development of neurodegenerative disease. However, the BDNF Val66Met polymorphism may not be involved in the pathogenesis of iRBD as well as phenoconversion in the studied population.

Introduction: Brain-derived neurotrophic factor (BDNF) plays an important role in the survival of dopaminergic neurons. Clinical studies have suggested that serum BDNF levels are reduced in patients with Parkinson’s disease (PD). However, no study has investigated peripheral BDNF levels and BDNF Val66Met polymorphism in the prodromal stage of PD and their relationship with disease conversion. Methods: 120 patients with video-polysomnographically (v-PSG) confirmed iRBD and 120 healthy controls (HCs) were enrolled. Genetic analyses were performed, and plasma levels of BDNF were measured. All patients with iRBD underwent comprehensive clinical testings, and 107 iRBD patients were prospectively followed-up. Results: Plasma BDNF levels were significantly lower in the iRBD group than in HCs (18878.85 pg/ml vs. 24649.85 pg/ml, p = 0.002), but no differences were observed in BDNF Val66Met carrier rates between the two groups. Plasma BDNF levels did not differ significantly between BDNF Val66Met carriers and non-carriers. Notably, higher plasma BDNF levels were associated with an increased risk of short-term disease con-version (Hazard Ratio = 3.418, 95% CI 1.520-7.684, p = 0.003), whereas BDNF Val66Met carrier rates showed no such association. Conclusion: Our findings suggest that plasma BDNF is significantly associated with iRBD and may likely serve as a prognostic biomarker for the development of neurodegenerative dis-ease. However, the BDNF Val66Met polymorphism may not be involved in the path-ogenesis of iRBD as well as phenoconversion in the studied population.

BACKGROUND:Early differentiation of multiple system atrophy (MSA) from Parkinson's disease (PD) remains difficult, particularly within two years of symptom onset, when diagnostic uncertainty has major implications for prognosis, referral, and trial enrolment. Because MSA is rare, previous biomarker studies have often been limited by relatively small samples and restricted multicentre validation. We aimed to determine the diagnostic performance of plasma neurofilament light chain (NfL) for differentiating MSA from PD and to assess the incremental value of glial fibrillary acidic protein (GFAP), total tau (t-tau), and phosphorylated tau at threonine 217 (p-tau217). METHODS:In this multicentre cross-sectional diagnostic study, participants were enrolled from five movement-disorder referral centres in China between Jan 1, 2018, and June 30, 2024, and were divided by enrolment period into discovery and temporally separated validation datasets. Plasma NfL, GFAP, t-tau, and p-tau217 were measured using light-initiated chemiluminescence assays. Group comparisons used age- and sex-adjusted models, and discrimination was assessed using receiver-operating-characteristic analysis with sensitivity, specificity, predictive values, and robustness analyses. FINDINGS:The analysis included 2408 participants: 782 (32.5%) with PD, 796 (33.1%) with MSA, and 830 (34.5%) healthy controls. NfL was the best single biomarker for differentiating MSA from PD in the discovery dataset (AUC 0.920, 95% CI 0.903-0.936). The discovery-derived cutoff of 41.3 pg/mL yielded sensitivity of 90.5% and specificity of 83.4% in the discovery dataset, and sensitivity of 86.7% and specificity of 85.5% in the validation dataset (AUC 0.924, 95% CI 0.898-0.948). In the early-stage subgroup, NfL retained strong performance (AUC 0.943, 95% CI 0.915-0.966). Integrated multimarker models provided limited incremental discrimination over NfL alone. INTERPRETATION:Plasma NfL may support the differentiation between clinically diagnosed MSA and PD, including early in the disease course. The limited added value of multimarker panels supports a simpler and more immediately translatable NfL-first strategy for diagnostically uncertain parkinsonism. FUNDING:National Natural Science Foundation of China; the Capital's Fund for Health Improvement and Research; Beijing Natural Science Foundation; Beijing Municipal Science and Technology Commission; Beijing Neurosurgical Institute; Beijing Traditional Chinese Medicine Science and Technology Development Fund.

Abstract Background Understanding disease natural history is important for the development of potential treatments for people with MSA. We describe the natural progression of early MSA in a Chinese population. Methods Observational, 12-month study conducted in 8 sites across China . Eligible participants were aged 40–75 years, with possible or probable MSA of the parkinsonian (MSA-P) or cerebellar (MSA-C) subtype, and anticipated survival of ≥ 3 years. Disease progression was analyzed using a linear mixed model of Total UMSARS (Part I + II) progression, including baseline, Month 6 and Month 12 data. Results A total of 89 participants with a mean ± SD time since diagnosis of 0.4 ± 0.6 years were enrolled. Of these 52% had MSA-C and 48% participants had MSA-P. The mean ± SE [95%CI] rate of Total UMSARS progression was 1.27 ± 0.13 [1.01, 1.53] points per month. Participants showed a progression of 0.64 ± 0.06 [0.51, 0.76] points/month on UMSARS Part I and 0.62 ± 0.07 [0.47, 0.77] points/month on UMSARS Part II. Differences in the rates of UMSARS progression between patients with MSA-P and MSA-C were not statistically significant ( p > 0.05). Conclusions This is the first multicenter natural history study of MSA progression conducted in China. While prior studies have indicated a predominance of MSA-C in Asian populations, we found a more even split of MSA-C and MSA-P subtypes. In this early population, patients showed an average progression rate of ~ 15 Total UMSARS points/year; rates of progression were similar between the two subtypes and were in alignment with previous studies that assessed disease progression using UMSARS in Western populations. Trial registration Clinicaltrals.gov, NCT05453058 (registered June 16, 2022).

BACKGROUND:Previous studies have suggested that metabolic alterations are involved in the pathogenesis of α-synucleinopathies. However, the metabolic changes in isolated REM sleep behavior disorder (iRBD), the prodromal stage of α-synucleinopathies, and their relationship to phenoconversion remain unexplored. OBJECTIVE:To investigate the serum metabolic markers in patients with iRBD and evaluate their association with the risk of conversion to α-synucleinopathies. METHODS:We enrolled 148 patients with video-polysomnography (vPSG)-confirmed iRBD and 142 age- and sex-matched healthy controls (HCs). 138 patients with iRBD were prospectively followed over an average duration of 3.67 years and 34 developed to α-synucleinopathies. Serum metabolic markers, including uric acid (UA), fasting blood glucose (FBG), homocysteine (Hcy), and lipid profile were measured at baseline. RESULTS:Compared with HCs, patients with iRBD exhibited significantly lower serum UA (332.15 μmol/L vs. 314.73 μmol/L, p = 0.010) and FBG (6.02 mmol/L vs. 5.69 mmol/L, p = 0.008) levels. Competing-risk regression analysis revealed that lower serum UA (hazard ratio [HR] 0.992, 95% CI 0.985-0.998, p = 0.013), higher Hcy (HR 1.070, 95% CI 1.028-1.113, p = 0.001), and higher FBG (HR 1.477, 95% CI 1.081-2.017, p = 0.014) were associated with an increased risk of conversion to dementia. CONCLUSION:Lower serum UA and FBG levels are potential risk factors for iRBD. Furthermore, distinct markers, including lower serum UA levels and elevated Hcy and FBG levels, were associated with an increased risk of dementia conversion. Our findings suggest that metabolic markers may be valuable indicators for predicting specific phenoconversion outcomes in iRBD.

Introduction: Freezing of gait (FOG) in advanced Parkinson's disease (PD) remains a therapeutic challenge, with conventional subthalamic nucleus deep brain stimulation (STN-DBS) demonstrating limited efficacy. Methods: This multicenter, prospective, single-blind study investigated the effects of combined high-frequency STN stimulation and ultra-low-frequency substantia nigra pars reticulata (SNr) stimulation in six PD patients with refractory FOG. Assessments included Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, New Freezing of Gait Questionnaire (NFOGQ), Gait and Falls Questionnaire (GFQ), and Schwab and England Activities of Daily Living (ADL) scale. Results: Dual-target stimulation significantly outperformed STN-only stimulation in improving appendicular motor symptoms (MDS-UPDRS Part III: p = 0.04 medication-ON, p = 0.009 medication-OFF) and reducing FOG severity (NFOGQ: p = 0.02, GFQ: p = 0.01 vs. STN-DBS). Postural stability remained unchanged, while ADL scores improved clinically (p = 0.04). Volume of tissue activated (VTA) analysis revealed more STN VTA connectivity in cerebrum, in contrast with more SNr VTA connectivity in cerebellum. Conclusion: These findings highlight the potential of dual-target free-frequency DBS for multimodal symptom control in PD and hopefully bring new sights in understanding mechanisms of DBS treatments in FOG.

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a well-established prodromal manifestation of α-synucleinopathies, with two principal phenoconversion trajectories: parkinsonism-first and dementia-first. Although subtle gait abnormalities have been observed prior to phenoconversion, their predictive value remains unclear. We investigated whether wearable sensor-based gait parameters are associated with phenoconversion and its clinical trajectories in iRBD. Sixty-eight polysomnography-confirmed iRBD patients and 61 healthy controls were enrolled at baseline. The iRBD cohort was followed for a mean of 3.68 years, with 21 patients converting to neurodegenerative diseases; 38 patients completed follow-up gait assessment. Participants performed one-minute walking trials under normal, fast, and dual-task conditions while wearing six inertial sensors. At baseline, iRBD patients exhibited significant gait abnormalities compared with controls. Several gait parameters were more strongly associated with subsequent conversion to Parkinson's disease (PD) than to dementia with Lewy bodies (DLB), including shorter stride length, greater swing time variability, reduced arm swing range, increased arm swing variability, and lower peak arm swing velocity. Longitudinally, converters showed a steeper decline in stride length and greater increases in dual-task cost. Wearable sensor-based gait assessment may serve as a digital biomarker for predicting phenoconversion in iRBD, particularly along the parkinsonism-first trajectory.

Purpose: Progressive supranuclear palsy (PSP) is a tauopathy marked by widespread tau aggregation and prominent monoaminergic dysfunction, yet the relationship between regional tau burden and monoaminergic impairment remains unclear. In this study, we determine whether regional tau burden is associated with nigrostriatal monoaminergic dysfunction in PSP using PET imaging. Patients and Methods: A subset of 20 patients with PSP and monoaminergic impairment, identified by 18 F-FP-DTBZ PET, was recruited and subsequently underwent 18 F-APN-1607 PET to assess tau deposition. All images were spatially normalized and analyzed based on predefined volumes of interest. Erosion-based cerebral white matter was used as the reference region to calculate standardized uptake value ratios (SUVRs) for 18 F-APN-1607 PET. Results: The SUVRs of 18 F-APN-1607 PET differed significantly between patients with PSP and healthy controls in the globus pallidus, substantia nigra, subthalamus nucleus, and red nucleus, while a significant difference in 18 F-FP-DTBZ SUVRs was observed in all the striatal regions and substantia nigra. Regression analysis discovered negative associations between tau load and monoaminergic disruption in the putamen and caudate, whereas tau accumulation in the substantia nigra was not significantly associated with nigrostriatal impairment. Conclusions: The pallido-nigro-luysian axis and nigrostriatal system serve as sensitive targets for detecting tau deposition and monoaminergic disruption in PSP. Local striatal tau pathology and tau burden were associated with monoaminergic disruption in PSP.

Mitochondrial dysfunction is central to Parkinson’s disease (PD), but assessing it in vivo remains challenging. Plasma L1CAM-immunocaptured putative neuron-derived exosomes (NDEs) offer minimally invasive access to brain molecular signatures. This study investigated whether mitochondrial complex (MC) proteins in NDEs are altered in PD and explored their association with clinical features. Plasma putative NDEs were isolated from 28 patients with PD and 33 normal controls (NCs) by L1CAM immunocapture. Levels of mitochondrial subunits—NDUFS3 (Complex I), UQCRC2 (Complex III), MT-CO1 (Complex IV), and ATP5F1A (Complex V)—and the antioxidant enzyme SOD1 were quantified by ELISA. Correlations with clinical severity and diagnostic performance were analyzed. Compared with NCs, PD patients exhibited significantly lower levels of NDUFS3 and UQCRC2 in NDEs (p < 0.05, after FDR correction). NDUFS3, UQCRC2, and SOD1 showed modest inverse correlations with motor symptom severity (R = −0.26). The NDUFS3/UQCRC2 combination yielded an AUC of 0.763 (95

This study explores the effect of risk factors on the progression of idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) to α-synucleinopathies in a Chinese cohort. Patients with iRBD were enrolled and assessed for environmental factors and lifestyle using standardized structured questionnaires at baseline. All patients were prospectively followed for phenoconversion monitoring. The cumulative incidence was estimated using survival analysis. Of 155 iRBD enrolled in the cohort, follow-up information was available in 141 patients. The phenoconversion rate was 16.3% after 3 years, 27.6% after 5 years, and 57.2% after 10 years. Eighteen participants converted within 3 years, 27 converted within 5 years, and 36 converted within 10 years. IRBD with positive family history of parkinsonism had an increased risk of being converted to α-synucleinopathies, while tea drinking was associated with a decreased phenoconversion risk. Our findings shed light on a potential application of tea drinking in modifying iRBD progression.

BACKGROUND:Individuals with rapid eye movement sleep behavior disorder (RBD) are considered to be at high risk of neurodegenerative diseases. RBD has been reported to be a male-predominant parasomnia and remains to be characterized in different population settings. We investigated sex-related differences in the prevalence, comorbidities, clinical characteristics, and prodromal neurodegenerative symptoms of possible RBD (pRBD) in a community-based cohort. METHODS:The validated RBD Questionnaire-Hong Kong (RBDQ-HK) was used to screen for pRBD among 7314 Chinese older adults (2881 men and 4433 women) in the Beijing Longitudinal Study on Aging (BLSA) II cohort. Demographic information, clinical features, prodromal non-motor symptoms, and subtle motor symptoms were assessed using established questionnaires. RESULTS:A total of 219 participants aged 55 or above were diagnosed with pRBD, of whom 60.27 % were women. The overall prevalence of pRBD was 3.03 %, with similar rates observed in men (3.06 %) and women (3.01 %). Women with pRBD were more likely to have a lower educational level (p < 0.001), higher body mass index (p = 0.030), and higher prevalence of hypertension (p = 0.044) and cardiovascular disease (p = 0.045). They had more frequent sad dreams (p = 0.009) and poorer sleep quality (p = 0.045), whereas men were more prone to hurt themselves or their bed partners in dreams (p = 0.031 and p = 0.019, respectively). No sex difference was found in non-motor symptoms; however, a greater proportion of men reported reduced arm swing (p = 0.031). CONCLUSIONS:In this community population-based study, we found that female participants with pRBD were less educated and exhibited fewer sleep-related injuries than males, which may lead to underreporting in clinical settings. However, males and females had a similar prevalence of prodromal neurodegenerative symptoms. Longitudinal studies are needed to further evaluate the sex differences in the risk of disease phenoconversion in isolated RBD patients in general populations.

Background Although dyskinesia is well recognized in Parkinson’s disease, it is generally underacknowledged in multiple system atrophy (MSA). Reported cases of dyskinesia primarily manifest in patients with MSA with predominant parkinsonism (MSA-P), and characteristically present as orofacial dystonia. However, we have observed other manifestations of dyskinesia in our clinical practice. The current report aims to present the specific manifestations of dyskinesia in MSA-P, with videos. Methods We enrolled six patients with MSA-P with dyskinesia from Xuanwu Hospital. Of these, four had clinically established MSA-P and two had clinically probable MSA-P according to the 2022 Movement Disorder Society criteria for MSA diagnosis. All six patients underwent an acute levodopa challenge test, and videos were recorded during the process. Results Dyskinesia had a unilateral distribution in four patients. Three patients presented with peak-dose orofacial dystonia; of these, two were associated with blepharospasm and two were associated with limb dystonia. In addition, we observed that one patient had peak-dose distal lower limb dystonia with upper limb chorea, one patient had wearing-off dystonia of the eyelids, and one patient had diphasic generalized chorea mimicking that of Parkinson’s disease. Conclusions In addition to orofacial dystonia, the topographic patterns of dyskinesia in MSA-P can manifest as limb dystonia, blepharospasm, and generalized chorea. Moreover, the temporal patterns of dyskinesia in MSA-P can be peak-dose, wearing-off, or diphasic.

In clinical specialties focusing on neurological disorders, there is a need for comprehensive and integrated non-invasive, sensitive, and specific testing methods. Both Parkinson’s disease and multiple system atrophy are classified as α-synucleinopathies, characterized by abnormal accumulation of α-synuclein protein, which provides a shared pathological background for their comparative study. In addition, both Parkinson’s disease and multiple system atrophy involve neuronal death, a process that may release circulating cell–free DNA (cfDNA) into the bloodstream, leading to specific alterations. This premise formed the basis for investigating cell–free DNA as a potential biomarker. Cell-free DNA has garnered attention for its potential pathological significance, yet its characteristics in the context of Parkinson’s disease and multiple system atrophy are not fully understood. This study investigated the total concentration, nonapoptotic level, integrity, and cell-free DNA relative telomere length of cell-free DNA in the peripheral blood of 171 participants, comprising 76 normal controls, 62 patients with Parkinson’s disease, and 33 patients with multiple system atrophy. In our cohort, 75.8% of patients with Parkinson’s disease (stage 1–2 of Hoehn & Yahr) and 60.6% of patients with multiple system atrophy (disease duration less than 3 years) were in the early stages. The diagnostic potential of the cell-free DNA parameters was evaluated using receiver operating characteristic (ROC) analysis, and their association with disease prevalence was examined through logistic regression models, adjusting for confounders such as age, sex, body mass index, and education level. The results showed that cell-free DNA integrity was significantly elevated in both Parkinson’s disease and multiple system atrophy patients compared with normal controls (P < 0.001 for both groups), whereas cell-free DNA relative telomere length was markedly shorter (P = 0.003 for Parkinson’s disease and P = 0.010 for multiple system atrophy). Receiver operating characteristic analysis indicated that both cell-free DNA integrity and cell-free DNA relative telomere length possessed good diagnostic accuracy for differentiating Parkinson’s disease and multiple system atrophy from normal controls. Specifically, higher cell-free DNA integrity was associated with increased risk of Parkinson’s disease (odds ratio [OR]: 5.72; 95% confidence interval [CI]: 1.54–24.19) and multiple system atrophy (OR: 10.10; 95% CI: 1.55–122.98). Conversely, longer cell-free DNA relative telomere length was linked to reduced risk of Parkinson’s disease (OR: 0.16; 95% CI: 0.04–0.54) and multiple system atrophy (OR: 0.10; 95% CI: 0.01–0.57). These findings suggest that cell-free DNA integrity and cell-free DNA relative telomere length may serve as promising biomarkers for the early diagnosis of Parkinson’s disease and multiple system atrophy, potentially reflecting specific underlying pathophysiological processes of these neurodegenerative disorders.

Background: Gait disturbance is a vital characteristic of motor manifestation in α– synucleinopathies, especially Parkinson’s disease. Subtle gait alterations are present in isolated rapid eye movement sleep behavior disorder (iRBD) patients before phenoconversion; it is yet unclear, if gait analysis may predict phenoconversion. Objective: To investigate subtle gait alterations and explore whether gait analysis using wearable sensors is associated with phenoconversion of iRBD to α-synucleinopathies. Methods: Thirty-one polysomnography-confirmed iRBD patients and 33 healthy controls (HCs) were enrolled at baseline. All participants walked for a minute while wearing 6 inertial sensors on bilateral wrists, ankles, and the trunk (sternal and lumbar region). Three conditions were tested: (i) normal walking, (ii) fast walking, and (iii) dual-task walking. Results: Decreased arm range of motion and increased gait variation (stride length, stride time and stride velocity) discriminate converters from HCs at baseline. After an average of 5.40 years of follow-up, 10 patients converted to neurodegenerative diseases (converters). Cox regression analysis showed higher value of stride length asymmetry under normal walking condition to be associated with an early conversion of iRBD to α– synucleinopathies (adjusted HR 4.468, 95% CI 1.088– 18.349, p = 0.038). Conclusions: Stride length asymmetry is associated with progression to α– synucleinopathies in patients with iRBD. Gait analysis with wearable sensors may be useful for screening, monitoring, and risk stratification for disease-modifying therapy trials in patients with iRBD.

Background and aims: Constipation is one of the most common nonmotor symptoms (NMSs) of Parkinson's disease (PD). The infection rate of Helicobacter pylori (HP) is greater in PD patients. This study was a multicenter prospective cohort study in which propensity score matching (PSM) was used to determine whether HP infection was a risk factor for constipation in patients with PD. Methods: A total of 932 PD patients with 13C-urea breath test for HP were included in the study. The PSM was estimated with the use of a nonparsimonious multivariate logistic regression model, with HP infection as the dependent variable and all the baseline characteristics as covariates. A total of 697 patients composed the study cohort, including 252 (36.2 %) patients in the HP-positive (HPP) group and 445 (63.8 %) patients in the HPnegative (HPN) group. Before PSM, there were differences in several of the baseline variables between the two groups. After PSM, 250 HPP patients were matched with 250 HPN patients and the standardized differences were less than 0.1 for all variables. Results: The present results demonstrate that HP infection is a risk factor for constipation in patients with PD [RR (95 % CI) 1.412 (1.155-1.727), P < 0.001]. Subgroup analyses revealed that HP infection was both a risk factor for constipation in Hoehn-Yahr scale (1,1.5) group and Hoehn-Yahr scale (2-5) group [OR (95 % CI) 1.811 (1.079-3.038), P < 0.025; OR (95 % CI) 2.041 (1.177-3.541), P < 0.011]. Conclusions: The results of our prospective cohort study suggest that Helicobacter pylori infection is a risk factor for constipation in patients with PD. Trial registration: ChiCTR2300071631.

BackgroundAlpha-synuclein oligomers (o-α-syn) are pivotal in the pathogenesis of α-synucleinopathy. Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) serves as an early indicator of the disease, offering insights into disease mechanisms and early intervention. Nevertheless, the diagnostic and predictive potential of o-α-syn in iRBD remains largely unexplored. This study aimed to evaluate the plasma levels of o-α-syn in patients and investigate their utility as biomarkers for diagnosis of and predicting phenoconversion in iRBD.MethodsA total of 143 participants, including 77 polysomnography-confirmed iRBD patients and 66 normal controls (NC), were recruited for this longitudinal observational study. Baseline clinical assessments and plasma collection were conducted for all iRBD patients, with 72 of them undergoing regularly prospective follow-up assessments for parkinsonism or dementia. Plasma levels of o-α-syn were quantified using enzyme-linked immunosorbent assay, and were compared between groups using a general linear model adjusted for age and sex. The diagnostic performance of plasma o-α-syn in iRBD was evaluated by area under the receiver operating characteristic curve (AUC) with 95% CI. Cox regression analysis and Kaplan–Meier survival curves were employed to assess the predictive value of plasma o-α-syn for phenoconversion in iRBD.ResultsPlasma o-α-syn levels did not exhibit statistically significant differences among iRBD converter patients, iRBD nonconverter patients, and NC. The AUC for distinguishing NC from iRBD was 0.52 (95% CI: 0.42–0.62, p = 0.682). Spearman correlation analysis revealed a significant positive correlation between plasma o-α-syn levels and MOCA scores in the iRBD group (p < 0.001). Subgroup analyses indicated that iRBD patients with cognitive decline (p = 0.058) and depressive symptoms (p = 0.017) had notably lower o-α-syn levels compared to those without such symptoms. Over a median follow-up period of 5.83 years, 26 iRBD patients developed neurodegenerative synucleinopathies. Cox regression and Kaplan–Meier survival curve analyses indicated that plasma level of o-α-syn lacked a predictive value for disease conversion in iRBD patients.ConclusionDespite a potential role in the pathophysiology of iRBD, o-α-syn are not appropriate biomarkers for diagnosing or predicting disease progression. While this study offers insights into the pathogenesis of iRBD and neurodegenerative synucleinopathies, further large-scale longitudinal studies are warranted to validate these findings.

Background: While multiple system atrophy (MSA) presents with high heterogeneous motor and nonmotor symptoms, the associations between clinical phenotypes and prognosis are unclear. Objective: We aimed to evaluate clinical phenotypes of MSA using data-driven approach and measure the impact of phenotypes on survival and bedbound status. Methods: 193 MSA patients were recruited from Xuanwu Hospital Capital Medical University, whose history, motor and non-motor symptoms were examined using cluster analysis. Ninety-five participants were followed-up via telephone after a mean of 31.87 months. We employed Kaplan– Meier analysis to examine survival and performed Cox and logistic regression analyses to identify factors associated with survival and bedbound status. Results: We identified four clinical profiles of MSA: cerebellar symptom-dominant, sleep and mood disorder-dominant, rigid akinetic-dominant, and malignant diffuse. The overall median survival was 7.75 years (95% CI 7.19–8.31). After adjusting for years from symptom onset to diagnosis, age and sex, patients in the malignant diffuse and rigid akinetic-dominant clusters had greater risk of death than sleep and mood disorder-dominant cluster. Furthermore, patients in the malignant diffuse and rigid akinetic-dominant clusters had higher risk of being bedbound than cerebellar symptom-dominant cluster. Conclusions: The malignant diffuse and sleep and mood disorder-dominant were identified besides the two classical subtypes, parkinsonism, and cerebellar symptom-variant. Patients with rigid-akinetic motor profiles have a worse prognosis than cerebellar symptom-dominant profiles in general. Diffuse symptoms, especially postural instability, and cognitive alterations at diagnosis, indicate rapid functional loss and disease progression. The different profiles and prognoses might indicate varied underlying pathological mechanisms.

Orthostatic hypotension (OH) is one of the most common symptoms in patients with multiple system atrophy (MSA). Vestibular system plays an important role in blood pressure regulation during orthostatic challenges through vestibular-sympathetic reflex. The current study aimed to investigate the relationship between vestibular function and OH in patients with MSA. Participants with MSA, including 20 with OH (mean age, 57.55 ± 8.44 years; 7 females) and 15 without OH (mean age, 59.00 ± 8.12 years; 2 females) and 18 healthy controls (mean age, 59.03 ± 6.44 years; 8 females) were enrolled. Cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs) tests were conducted to evaluate vestibular function. Patients with MSA presented with significantly higher rate of absent cVEMPs (57.1

Background: As a biomarker targeting vesicular monoamine transporter 2 (VMAT2), F-18-9-fluoropropyldihydrotetrabenazine (F-18-FP-DTBZ) positron emission tomography (PET) is highly accurate in diagnosing Parkinson's disease (PD) and assessing its severity. However, evidence is insufficient in patients with progressive supranuclear palsy (PSP). Objective: We evaluated the striatal and extrastriatal monoaminergic disruption of PSP and differences in patterns between patients with PSP, PD, and healthy controls (HCs) using F-18-FP-DTBZ PET, as well as its correlations with the clinical characteristics of PSP. Methods: We recruited 58 patients with PSP, 23 age- and duration-matched patients with PD, as well as 17 HCs. Patients were scanned using F-18-FP-DTBZ PET/computed tomography, and images were spatially normalized and analyzed based on the volume of interest. Results: VMAT2 binding differed significantly in the striatum and substantia nigra among the groups (P < 0.001). A more severe disruption in the caudate was noted in the PSP group (P < 0.001) than in the PD group. However, no differences were found in the nucleus accumbens, hippocampus, amygdala, or raphe between the PD and PSP groups. Within the PSP group, striatal VMAT2 binding was significantly associated with the fall/postural stability subscore of the PSP Rating Scale, especially in the putamen. Furthermore, VMAT2 binding was correlated with Mini-Mental State Examination or Montreal Cognitive Assessment in the hippocampus. Conclusions: Caudate disruptions showed prominent differences among the groups. VAMT2 binding in the striatum and hippocampus reflects the severity of fall/postural stability and cognition, respectively. (c) 2024 International Parkinson and Movement Disorder Society. (c) 2024 International Parkinson and Movement Disorder Society.