Journal of Parkinson's disease最新文献

{"title":"Association between age at Parkinson's disease onset and divorce: An exploratory analysis from the fox insight cohort.","authors":"Katarzyna Smilowska, Orsolya Makos, Alay Rangel Cristales, Raja Mehanna, Jori Fleisher, Kishore R Kumar, Roy N Alcalay, Mehri Salari, Victor McConvey, Baorong Zhang, Rodolfo Savica, Daniel J Van Wamelen","doi":"10.1177/1877718X261479270","DOIUrl":"10.1177/1877718X261479270","url":null,"abstract":"<p><p>BackgroundParkinson's disease (PD) typically presents after age 60; however, approximately 10% of individuals experience early-onset PD (EOPD), with symptoms beginning between ages 21 and 50. Beyond motor and non-motor symptoms, PD can impact personal relationships through stigma, social isolation, and emotional burden. This study aims to examine the influence of PD on relationship outcomes such as divorce or separation.MethodsThis exploratory study analyzed data from the Fox Insight cohort, an online longitudinal research initiative supported by The Michael J. Fox Foundation. We included 470 individuals with self-reported PD who had complete data on marital status (\"married\" or \"divorced\") and age at PD onset. Participants were categorized as having EOPD (<50 years) or late-onset PD (≥50 years). Chi-square tests assessed the association between PD onset group and marital status. A binary logistic regression model further evaluated gender and onset age as predictors of marital status in a subset of 330 participants.ResultsA significant association was found between PD onset group and marital status, with a higher divorce rate among the EOPD group (17.5%; 7/40) compared to late-onset PD (6.1%; 26/430) (p = 0.017). Logistic regression revealed no statistically significant predictors, though trends suggested lower odds of divorce in men and those with late-onset PD.ConclusionThis exploratory analysis identified a potential association between early PD onset and higher divorce rates; however, with only 7 events in 40 EOPD participants, this finding is inherently unstable and should be regarded as hypothesis-generating only. Confirmation in larger, longitudinal cohorts is required before any conclusions can be drawn.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261479270"},"PeriodicalIF":5.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking the concept of disease modification in an evolving Parkinson's disease treatment landscape.","authors":"Angelo Antonini, Robert E Gross, Maria De Leon, Kevin Kwok, Tom Foltynie, Günter Höglinger, Thomas Gasser, Jean-Christophe Corvol, David J Pedrosa, Jens Volkmann, Claire Henchcliffe","doi":"10.1177/1877718X261481704","DOIUrl":"10.1177/1877718X261481704","url":null,"abstract":"<p><p>We are in an era in which increasing numbers of potentially disease-modifying treatments for Parkinson's disease are being tested in clinical development. Current definitions of disease modification have inherent limitations; hence there is a need to establish a clear, unified definition. This unified definition of disease modification should be applicable to both idiopathic and genetic forms of Parkinson's disease. In addition to motor function, it must address important milestones (e.g., cognition, autonomic dysfunction) across all disease stages. This review examines existing definitions and highlights the need for a more holistic approach that integrates the perspectives of patients, healthcare professionals, and researchers.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261481704"},"PeriodicalIF":5.9,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of a novel strategy to increase participation of Black and Hispanic people in parkinsonism research.","authors":"Dalilah F Quintana Mora, Anya C McGoldrick, Yolfrankcis Mendez, Alessandra Cervera, Parul Agarwal, John F Crary, Ruth H Walker, Melissa J Nirenberg","doi":"10.1177/1877718X261487914","DOIUrl":"10.1177/1877718X261487914","url":null,"abstract":"<p><strong>Introduction: </strong>Black and Hispanic people are underrepresented in parkinsonism research leading to critical knowledge gaps and reduced quality of care.</p><p><strong>Methods: </strong>We developed a novel, comprehensive clinical registry in which research eligibility, interest, and participation are actively tracked for all patients at our site to reduce selection bias and streamline recruitment. We also implemented targeted approaches to reduce psychosocial and sociocultural barriers to research participation of Black and Hispanic people. We then performed a retrospective chart review to test the hypothesis that these combined strategies would be associated with racially/ethnically unbiased research recruitment. All follow-up patients with degenerative parkinsonism seen at the Bronx Veterans Affairs Medical Center over a 19-month period were included in the analysis. Primary outcome measures were the approach and acceptance rates for CANPARK, a single-center prospective observational cohort study of American military veterans with parkinsonism.</p><p><strong>Results: </strong>During the study window, 197 parkinsonism patients were seen, 192 were eligible for CANPARK [ages 53-91; 96.4% male; 29.7% Hoehn and Yahr ≥4; 25.0% atypical parkinsonism], 167 (87.0% of eligible patients) were invited to participate (similar in all racial/ethnic groups), and 128 of 159 patients who made a decision whether to participate (80.5%) agreed to enroll. Acceptance rates were comparable in Black (79.4%; p = 0.92) or Hispanic (87.5%; p = 0.43) versus White (80.2%) patients.</p><p><strong>Conclusions: </strong>Using a novel, real-time clinical registry and targeted approaches, we achieved unbiased recruitment and high participation of Black and Hispanic patients in parkinsonism research. Future studies are needed to evaluate these approaches in other clinical settings.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261487914"},"PeriodicalIF":5.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co- and multipathologies need serious consideration for understanding Parkinson's disease pathogenesis and designing novel experimental therapeutic strategies.","authors":"Ashley Boehringer, Lorraine V Kalia, Bastiaan R Bloem, Jeffrey H Kordower","doi":"10.1177/1877718X261486172","DOIUrl":"10.1177/1877718X261486172","url":null,"abstract":"","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261486172"},"PeriodicalIF":5.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of α-synuclein seeding activity in tear fluid as a candidate biomarker for Parkinson's disease.","authors":"Asako Kakimoto, Katsuya Satoh, Tomoko Tsukahara-Kawamura, Yoshio Tsuboi","doi":"10.1177/1877718X261486736","DOIUrl":"10.1177/1877718X261486736","url":null,"abstract":"<p><p>BackgroundParkinson's disease (PD) is an α-synucleinopathy, and pathological α-synuclein (α-Syn) is detectable in peripheral tissues and fluids. However, the diagnostic utility of tear fluid as a minimally invasive source for α-Syn seed detection remains unclear. We aimed to detect α-Syn seeds in tear fluid and evaluate the clinical characteristics of α-Syn-positive patients.MethodsTear fluid was collected bilaterally using Schirmer strips. The α-Syn seeding amplification assay (αSynSAA) was performed using the real-time quaking-induced conversion (RT-QuIC) protocol. We analyzed 55 patients with PD and 40 control participants.ResultsThe αSynSAA revealed α- synuclein seeding activity in tear fluid, showing 52.7% sensitivity and 100% specificity. αSyn SAA-positive patients had higher Movement Disorder Society-Unified Parkinsons Disease Rating Scale part III scores than αSyn SAA-negative patients. α-Syn seeding activity was detected in tear fluid from some patients with PD but not in disease controls.ConclusionThis study demonstrates the feasibility of αSynSAA analysis in tear fluid, highlighting its potential as a novel substrate for biomarker development. Further studies in related synucleinopathies and in early or prodromal PD are needed to validate these findings and assess the diagnostic performance of this tear-based assay.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261486736"},"PeriodicalIF":5.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive and motor profiles in biologically defined Parkinson's and Alzheimer's disease.","authors":"Daniel Zarhin, Noa Bregman, Tamara Shiner, Anat Mirelman, Roy N Alcalay, Avner Thaler","doi":"10.1177/1877718X261477521","DOIUrl":"10.1177/1877718X261477521","url":null,"abstract":"<p><p>BackgroundParkinson's disease (PD) patients may harbor coexisting Alzheimer's disease (AD) pathology that accelerates cognitive and motor decline. Defining biomarker-defined AD in PD is important for prognosis, patient counseling, and trial stratification.ObjectiveTo determine the prevalence of AD biomarker positivity in α-synuclein seed amplification assay (αSyn-SAA) positive PD and assess its impact on cognitive and motor progression.MethodsWe analyzed data from the Parkinson's Progression Markers Initiative, a multinational prospective cohort of de novo PD patients. Baseline CSF biomarkers included αSyn-SAA, amyloid-β1-42 (Aβ1-42), and phosphorylated tau181 (p-tau181). AD biomarker positivity was defined by a low Aβ1-42/high p-tau181 profile using the CSF Aβ1-42/p-tau181 ratio (<39.2). αSyn-SAA-positive PD participants with and without AD biomarker positivity were compared. Outcomes included cognition, Montreal Cognitive Assessment (MoCA), neuropsychological testing, and MDS-UPDRS motor scores over follow-up.ResultsAmong 449 αSyn-SAA-positive PD patients, 42 (9.3%) met AD biomarker criteria (PD-AD). Baseline cognition and motor scores did not differ between PD-AD and PD without AD biomarkers (PD-nonAD). Over time, PD-AD patients showed greater cognitive decline, with lower MoCA scores and higher MCI prevalence at 5 years. At 8 years, PD-AD patients also demonstrated worse motor outcomes. MoCA <24 predicted AD biomarker positivity (PPV 15%; OR 6.1). APOE ε4 status was not associated with cognition.ConclusionsBiomarker-defined AD identifies a distinct PD subgroup with accelerated cognitive and motor decline, independent of APOE ε4. A ratio-based CSF Aβ1-42/p-tau181 framework offers a practical approach to detect AD copathology in PD and refine prognostic stratification.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261477521"},"PeriodicalIF":5.9,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Juvenile Parkinson's disease: Symptom burden and treatment challenges.","authors":"Lorenzo Malfer, Capucine Piat, Aidan F Mullan, Ryan J Uitti, Leonardo G Fugoso, Elizabeth A Coon, James H Bower, Keith A Coffman, Rodolfo Savica","doi":"10.1177/1877718X261473047","DOIUrl":"10.1177/1877718X261473047","url":null,"abstract":"<p><p>Juvenile Parkinson's disease (JPD) is a rare condition characterized by the onset of parkinsonian motor symptoms before the age of 21. Sixteen patients with JPD who presented to the Mayo Clinic between 1990-2020 were included. The median age of symptoms onset was 18.5 years, and six cases had pathogenic <i>PRKN</i> mutations. Resting tremor was the most frequent initial symptom (81.3%), and non-motor symptoms were notably common, including mild cognitive impairment (56.3%), anxiety (62.5%), and depression (56.3%). Levodopa responsiveness was suboptimal in 9 patients and 14 exhibited motor fluctuations. JPD demonstrates distinct clinical characteristics compared with early-onset and late-onset PD.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1351-1354"},"PeriodicalIF":5.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13443335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond motor fluctuations: Understanding the clinical correlates of OFF burden in Parkinson's disease.","authors":"David Ledingham, Sahana Sathyanarayana, Robyn Iredale, Charlotte B Stewart, Victoria Foster, Debra Galley, Mark R Baker, Nicola Pavese","doi":"10.1177/1877718X261442857","DOIUrl":"10.1177/1877718X261442857","url":null,"abstract":"<p><p>BackgroundHistorically, OFF burden in Parkinson's disease has been primarily attributed to motor features. Recent studies highlight that non-motor symptoms, and the predictability of OFF episodes also drive functional impairment, yet they are rarely measured in clinical practice.ObjectiveTo identify which clinical features are most closely associated with OFF time and OFF impact, and to quantify the added explanatory value of temporal predictability, non-motor, and behavioural domains beyond a core motor model.MethodsWe analysed 1252 OFF-only visits from 430 PPMI participants. Outcomes were MDS-UPDRS IV 4.3 (OFF time) and 4.4 (OFF impact). Linear mixed-effects models with a participant random intercept were fitted. The core motor model included OFF-state motor severity, freezing, tremor, levodopa responsiveness, and dyskinesia, plus covariates. Predictability (IV 4.5), non-motor (mood, fatigue/sleep, autonomic/GI), and behavioural (impulse-control behaviours) domains were then added to assess added influence beyond motor. Analyses were stratified by time since diagnosis (Pooled; ≤ 4 y; ≥ 6 y).ResultsClinical features explained more variance in OFF impact than OFF time (25.9% vs 8.1%). OFF time was primarily linked to OFF-state motor severity/freezing, with levodopa responsiveness important early. For OFF impact, predictability produced the largest increment in marginal R² beyond the core motor model (pooled and Late). Within the core motor model, tremor was the largest contributor to OFF impact.ConclusionsPredictability is a prominent correlate of OFF impact. Asking about predictability may help tailor therapy, from timing optimisation to on-demand rescue for unpredictable episodes.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1211-1222"},"PeriodicalIF":5.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13454246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural biology of alpha-synuclein amyloid filaments: Implications in synucleinopathies.","authors":"Phelippe do Carmo Gonçalves, Irina Fernández, Claudio O Fernández Outón","doi":"10.1177/1877718X261461375","DOIUrl":"10.1177/1877718X261461375","url":null,"abstract":"<p><p>Synucleinopathies are a group of neurodegenerative disorders characterized pathologically by the presence of neuronal and/or oligodendrocyte inclusions composed of aggregated alpha-synuclein (αS). These disorders can be divided into two major sub-types: Lewy body disease and multiple system atrophy, which have distinct clinical and pathological profiles. As is seen with other neurodegenerative diseases, recent evidences suggest that the conformation and molecular organization of αS amyloid filaments deposited in brains might dictate the distinct pathological and clinical profiles in synucleinopathies. Resolving the structure of disease-specific αS aggregates becomes, therefore, of clinical interest. Until recently, the specific conformations of these aggregates at molecular resolution have remained elusive. This is now possible due to the advent and development of cryo-electron microscopy (cryo-EM) technology. This review aims to cover the recent advances in the structural biology of αS amyloid filaments implicated in synucleinopathies, raising a number of critical questions that continue to be investigated. What can we learn from these structures? What are the main structural differences between experimental systems and human tissue derived protein aggregates? What factors drive these differences? Do the amplified assemblies represent faithfully the seed structures? How these new findings improve our understanding of the molecular mechanisms behind fibril formation in disease? Can this knowledge be exploited for the design of diagnostic and therapeutical strategies? These aspects and the recent advances in the field will be addressed and discussed in this work.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1094-1114"},"PeriodicalIF":5.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13443150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient health literacy as a critical missing component in the PLAN to address the Parkinson pandemic.","authors":"Paula Abola, Benjamin Wolden, Alessandra Swarowsky, Mitchell Wolden","doi":"10.1177/1877718X261469382","DOIUrl":"10.1177/1877718X261469382","url":null,"abstract":"","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1340-1341"},"PeriodicalIF":5.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13438765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}