Journal of Parkinson's disease最新文献

{"title":"Optimizing participant recruitment and retention in clinical studies by hearing the voices of persons with Parkinson's.","authors":"Xiao Yue Goh, Cholpon Shambetova, Tzi Shin Toh, Eliza Zhunusova, Yi Wen Tay, Jun Ping Chua, Winn Hui Han, Joanne Yu Li Lim, Ai Huey Tan, Shen-Yang Lim","doi":"10.1177/1877718X261479268","DOIUrl":"10.1177/1877718X261479268","url":null,"abstract":"<p><p>BackgroundRecruitment and retention remain major barriers to clinical research in Parkinson's disease (PD).ObjectiveWe reviewed the literature on barriers and facilitators to PD research participation, and explored motivations, perceptions, and preferences regarding clinical research participation among \"underrepresented\" populations (URPs) in Asia.MethodsWe reviewed published studies examining recruitment and retention in PD research. In parallel, questionnaires were administered to patients in Malaysia and Kyrgyzstan (n = 92) to assess motivations for participation, project-related preferences, and willingness to engage in different types of research. Findings from the literature and survey, and the authors' real-world research experiences were synthesized to identify practical strategies for improving participation.ResultsKey barriers identified from the literature included limited awareness of research, logistical and financial burden, disease-related disability, mistrust, stigma, and technological challenges. Across both Asian cohorts, altruistic motivations, trust in clinicians and researchers, perceived personal and societal benefit, and appreciation of healthcare services strongly influenced willingness to participate in research. Minimizing inconvenience and avoiding invasive procedures were rated as important. Most patients were willing to participate in longitudinal studies, digital monitoring, and biosample collection involving saliva, blood, urine, and stool, whereas cerebrospinal fluid sampling and brain donation were less acceptable. Solutions include integrating research into routine care, culturally-sensitive communication, patient-friendly study designs, return of research results, active engagement of URPs, and greater patient involvement throughout the research process.ConclusionsBarriers to PD research participation are multifactorial. Patient-centred, culturally-sensitive, and trust-based approaches that reduce burden while enhancing inclusivity and communication may promote more sustainable research programs.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261479268"},"PeriodicalIF":5.9,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765107","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":"Environmental hazards and climate change: Unmasking Parkinson's hidden enemies.","authors":"Gerard Saranza, Szu-Ju Chen, Yue Leon Guo, Shaimaa Abdelaziz, Cezar Thomas Suratos, Kruzette Solijon, Roongroj Bhidayasiri, Ali Shalash, Chin-Hsien Lin","doi":"10.1177/1877718X261479272","DOIUrl":"https://doi.org/10.1177/1877718X261479272","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a multifactorial neurodegenerative disorder shaped by interactions between genetic susceptibility, environmental exposures, and broader ecological change. Although pesticides, industrial solvents, heavy metals, and air pollutants have long been implicated as potentially modifiable PD risk factors, climate change is now reshaping and amplifying these hazards through rising temperatures, worsening air quality, increased pesticide demand, extreme weather events, and wildfire-related particulate matter.This narrative review moves beyond a conventional exposure-based summary by integrating environmental toxicology, climate science, epidemiology, and mechanistic neuroscience to reframe PD risk within the context of planetary health. We summarize evidence linking major environmental hazards to PD pathogenesis, emphasizing convergent mechanisms such as oxidative stress, mitochondrial dysfunction, impaired proteostasis, neuroinflammation, blood-brain barrier disruption, and α-synuclein aggregation. We further discuss how climate-related changes may intensify these pathways and disproportionately affect vulnerable populations, including agricultural workers, older adults, socioeconomically disadvantaged communities, and individuals living in rapidly industrializing or climate-sensitive regions. Importantly, we highlight clinical and public health implications by proposing that structured environmental and occupational exposure assessment should be incorporated into PD risk evaluation, early recognition, preventive counseling, and research design. We also discuss exposure reduction, workplace protection, environmental monitoring, and regulatory policy as prevention-oriented strategies. By positioning environmental hazards and climate change as interconnected, underrecognized, and potentially modifiable contributors to PD, this review provides a framework for clinicians, researchers, and policymakers seeking to reduce the future global burden of neurodegenerative disease.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261479272"},"PeriodicalIF":5.9,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13473223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758665","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":"PT320, a GLP-1 receptor agonist, mitigates nucleus accumbens-associated depression- and anxiety-like behaviors in MitoPark mice of Parkinson's disease.","authors":"Kuan-Yin Tseng, Tung-Tai Kuo, Pi-Kai Chang, Jian-Liang Chou, Eagle Yi-Kung Huang, Nigel H Greig, Ho-Il Choi, Lars Olson, Barry J Hoffer, Yuan-Hao Chen","doi":"10.1177/1877718X261477621","DOIUrl":"10.1177/1877718X261477621","url":null,"abstract":"<p><p>BackgroundNeuropsychiatric symptoms such as anxiety and depression substantially impair quality of life in Parkinson's disease (PD), yet the underlying neural circuits remain poorly defined. The MitoPark (MP) mouse, a dopaminergic mitochondrial dysfunction model, recapitulates both motor and non-motor features of PD.ObjectiveTo determine whether the sustained-release GLP-1 receptor agonist PT320 (exenatide) alleviates anxiety- and depression-like behaviors in MP mice and to identify the involved neural substrates.MethodsThe temporal progression of anxiety- and depression-like behaviors was characterized in MP mice. PT320 was administered biweekly starting at either 5 weeks (early treatment) or 15 weeks (late treatment), with longitudinal evaluation until 20 weeks. Behavioral outcomes were correlated with molecular, transcriptomic, and neurochemical analyses in the nucleus accumbens (NAc), including Western blotting, bulk RNA sequencing, fast-scan cyclic voltammetry, and tyrosine hydroxylase immunostaining.ResultsEarly PT320 treatment effectively prevented the emergence of anxiety- and depression-like phenotypes in MP mice. Behavioral improvement was associated with restoration of BDNF signaling and activation of the Akt-CREB pathway in the NAc. Transcriptomic analysis revealed increased expression of Akt3, CREB, BDNF, and TrkB, along with modulation of genes related to mitochondrial homeostasis. Late PT320 treatment partially ameliorated neuropsychiatric deficits, coinciding with enhanced phasic dopamine release and recovery of tyrosine hydroxylase expression in the NAc.ConclusionsThese findings identify the NAc as a critical regulator of affective disturbances in this PD model. By restoring neurotrophic signaling and dopaminergic function, PT320 represents a promising therapeutic strategy for PD-related anxiety and depression.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261477621"},"PeriodicalIF":5.9,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13473357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726264","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-behavioral therapy in people with Parkinson's disease and caregivers: A mixed method systematic review on clinical applications and therapeutic outcomes.","authors":"Francesca Proietti, Simone Migliore, Chiara Longo, Francesca Lea Saibene, Giuseppe Curcio, Maria Chiara Malaguti, Mario Meloni, Edoardo Bianchini, Massimo Marano","doi":"10.1177/1877718X261457793","DOIUrl":"10.1177/1877718X261457793","url":null,"abstract":"<p><p>BackgroundCognitive behavioral therapy (CBT) has emerged as a promising intervention in Parkinson's disease (PD), although the available evidence remains heterogeneous in design and quality.ObjectiveThe present mixed method systematic review aims to synthesize the evidence on CBT in people with PD (PwPD) and caregivers, focusing on clinical applications and therapeutic outcomes across symptom domains.MethodsA systematic search of PubMed, Web of Science, Scopus and Cochrane databases was conducted for studies published between 1980 and 2025, following PRISMA guidelines. Eligible studies evaluated clinical applications and therapeutic outcomes of CBT-based interventions in PwPD and/or caregivers and included randomized controlled trials, observational studies, case series and single-case reports. Findings were synthesized narratively, and certainty of evidence was assessed using a simplified GRADE approach.ResultsFifty-four studies met inclusion criteria. The most robust evidence was observed for depression, with several RCTs supporting the efficacy of CBT, resulting in moderate certainty of evidence. Evidence for anxiety and sleep disorders suggests potential benefit; however, certainty was low due to heterogeneity and small sample sizes. Evidence for impulse control disorders, cognitive outcomes, motor symptoms, and caregiver -related outcomes remain limited, with low to very low certainty, Effects on motor symptoms were inconsistent and likely indirect.ConclusionsCBT represents a flexible and transdiagnostic intervention for treating non-motor symptoms in PwPD and for caregivers. While moderate-certainty evidence supports CBT use for depression, evidence for other domains remains limited. These findings should be interpreted with caution, and further large-scale, well designed RCTs are needed to strengthen the evidence base and clarify optimal therapeutic targets and delivery format.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261457793"},"PeriodicalIF":5.9,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13473367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712701","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":"A qPCR-based approach targeting the microbial gene marker <i>nanA</i> of mucin-degrading <i>Akkermansia</i> in Parkinson's disease.","authors":"Yasuaki Mizutani, Tadashi Fujii, Yasuhiro Maeda, Kohei Funasaka, Eizaburo Ohno, Yoshiki Hirooka, Hirohisa Watanabe, Takumi Tochio","doi":"10.1177/1877718X261462342","DOIUrl":"10.1177/1877718X261462342","url":null,"abstract":"<p><p>BackgroundParkinson's disease (PD) is a multifactorial neurodegenerative disorder increasingly linked to gut microbiota alterations. However, despite advances in fecal microbiota profiling as a non-invasive approach to disease risk assessment, its clinical utility remains limited by a lack of functionally relevant microbial biomarkers.ObjectiveThis cross-sectional study aimed to identify a microbial gene marker reflecting metabolic potential associated with both the presence and severity of PD.MethodsFecal samples from patients with PD (<i>n</i> = 59) and healthy controls (<i>n</i> = 65) were analyzed by 16S rRNA sequencing to characterize taxonomic profiles. Quantitative PCR (qPCR) targeted the consensus sequence of the mucin-degrading <i>nanA</i> gene (<i>nan_Akk</i>), a highly conserved within <i>Akkermansia nan</i> gene clusters. Differences in taxonomic composition and <i>nan_Akk</i> abundance were examined, and correlations with clinical severity scores evaluated in the PD group.ResultsPatients with PD showed reduced abundance of short-chain fatty acid-producing taxa (<i>Faecalibacterium</i>, <i>Blautia</i>, and <i>Anaerostipes</i>) and increased levels of <i>Akkermansia</i>. <i>Akkermansia</i> abundance correlated positively with motor severity, including Hoehn-Yahr stage. Moreover, <i>nan_Akk</i> levels also correlated positively with Hoehn-Yahr stage and were significantly elevated in PD patients compared with controls. Levels in the stage 4-5 group exceeded those in the stage 1-3 group (<i>P</i> = 0.0202), indicating a stage-related increase in mucin-degrading <i>nan_Akk</i> abundance.ConclusionsWe have identified <i>nan_Akk</i> as a microbial gene marker associated with both the presence and severity of PD. Our qPCR-based quantification shows potential as a non-invasive biomarker for disease stratification.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261462342"},"PeriodicalIF":5.9,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706915","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":"<i>GBA1</i> variants and mortality in Parkinson's disease: A systematic review and meta-analysis.","authors":"Nathan Chan, Anthony Raphael, Justin Kim, Amy Haryanto, Saman Heshmat, Tien K Khoo","doi":"10.1177/1877718X261470604","DOIUrl":"10.1177/1877718X261470604","url":null,"abstract":"<p><p>BackgroundVariants in the <i>GBA1</i> gene are a common genetic risk factor for Parkinson's disease (PD). While <i>GBA1</i>-PD is associated with more rapid motor and cognitive decline, evidence regarding impact on survival remains debatable.ObjectivesThis systematic review and meta-analysis synthesizes longitudinal evidence of <i>GBA1</i> variants as a prognostic factor for all-cause mortality in PD.MethodsWe searched MEDLINE, Embase, Cochrane (CENTRAL), ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform for studies comparing mortality in <i>GBA1</i>-PD versus non-carriers from inception to September 2025. Risk of bias was assessed using the Quality in Prognosis Studies tool. Hazard Ratios were pooled using a random-effects meta-analysis. Subgroup analysis was stratified by variant severity.ResultsEight studies (<i>N</i> = 13,690) were included. The primary meta-analysis (<i>n</i> = 4947) revealed <i>GBA1</i> variants were associated with significantly increased all-cause mortality risk versus non-carriers (HR 1.53, 95% CI 1.24-1.87; <i>I</i>² = 0.7%). A subgroup analysis suggested a possible severity-dependent effect, with severe variants showing higher point estimates (HR 1.87; 95% CI 1.24-2.82) than mild variants (HR 1.38; 95% CI 1.03-1.83), although the test for subgroup differences was not statistically significant.Conclusions<i>GBA1</i> variants are a significant prognostic marker for reduced survival in PD. This risk may increase with variant severity and persist after adjustment for dementia in the studies that examined this, although the available data is limited. Limitations include heterogeneous screening methods and predominance of European ancestry in study populations. <i>GBA1</i> status should be considered a significant prognostic factor for stratification in clinical trials and management.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261470604"},"PeriodicalIF":5.9,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684985","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":"Lack of genetic evidence for a role of SLC25A46 in alpha-synucleinopathies.","authors":"Han Yu, Sitki Cem Parlar, Konstantin Senkevich, Emma N Somerville, Zhao Zhang, Lang Liu, Meron Teferra, Jamil Ahmad, Farnaz Asayesh, Guy A Rouleau, Ziv Gan-Or","doi":"10.1177/1877718X261452773","DOIUrl":"10.1177/1877718X261452773","url":null,"abstract":"<p><p>BackgroundThe <i>SLC25A46</i> gene encodes a mitochondrial carrier protein previously implicated in neuropathy and optic atrophy. Biallelic variants in <i>SLC25A46</i> have been described in patients with Parkinson's disease (PD) with optic atrophy, but the evidence supporting a role in PD remains limited.ObjectiveTo assess whether <i>SLC25A46</i> variants contribute to PD, REM sleep behavior disorder (RBD), or dementia with Lewy bodies (DLB).MethodsWe examined common variants using four representative PD genome-wide association studies (GWAS) and an RBD GWAS and applied summary-data-based Mendelian randomization (SMR) to evaluate whether genetically regulated expression of <i>SLC25A46</i> shows a causal association with the risk of PD or RBD. Rare variant analyses were conducted in four cohorts of European descent: Accelerating Medicines Partnership: Parkinson's Disease (AMP-PD) PD (3,051 PD, 3,667 controls), UK Biobank (3,267 PD, 14,939 proxy, 54,800 controls), RBD (1,376 RBD, 2,580 controls), and AMP-PD DLB (2,605 DLB, 1,894 controls). Optimal sequence kernel association test (SKAT-O) and meta-analysis were used to assess rare variants.ResultsNo associations were observed between <i>SLC25A46</i> variants and PD, RBD, or DLB. SMR analyses revealed no evidence supporting a causal relationship between <i>SLC25A46</i> expression and PD or RBD risk. Rare variant burden analyses did not identify significant associations after multiple-testing correction across cohorts or meta-analyses.Conclusion<i>SLC25A46</i> variants showed no evidence of association, suggesting the gene does not play a major role in PD, RBD, or DLB risk.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261452773"},"PeriodicalIF":5.9,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meditation and breathwork on anxiety in Parkinson's disease: A pilot randomized controlled trial.","authors":"Akila Rayapuraju, Preeti U Reed, Jennifer Liu, Mei Chen, Morgan Pratt, Tulsi Chase, Victor Novack, Daniel Weintraub, David K Simon, Balachundhar Subramaniam","doi":"10.1177/1877718X261463924","DOIUrl":"10.1177/1877718X261463924","url":null,"abstract":"<p><p>BackgroundAnxiety and other non-motor symptoms can greatly diminish quality of life in people with Parkinson's Disease (PD). Yet, few randomized controlled trials (RCTs) have assessed accessible, non-pharmacological mental health treatments for people with PD.ObjectiveTo assess the feasibility and impact of brief, remotely-delivered meditation and breathwork on neuropsychiatric symptoms in people with PD.MethodsIn this 18-week RCT, intervention participants attended weekly webinars for six weeks, while waitlisted controls maintained their usual routine before crossing over at six weeks. Participants were assessed for weekly compliance trends (primary outcome) and changes in anxiety (primary outcome), depression, perceived stress, and other non-motor symptoms at 6-week intervals: baseline and weeks 6 (T2), 12 (T3), and 18 (T4). Weekly compliance was collected in each group for 12 weeks. Anxiety was measured using the Parkinson's Anxiety Scale.ResultsThere was a significant decrease in the primary outcome, anxiety, in the intervention group (n = 17) compared to the waitlist control (n = 21) after 6 weeks of meditation and breathwork practice (mean difference (MD)= -5.0, 95% CI [-9.5, -0.49], <i>P</i> = .03). Within-group analysis further confirmed a significant reduction in anxiety (MD = -4.7, 95% CI [2.10,7.33], <i>P</i> < .001) in the intervention group (n = 28). Thirty-one percent of participants met the compliance definition.ConclusionRemotely-delivered meditation and breathwork through the BSM program significantly reduced anxiety in individuals with PD in our study and may be a promising non-pharmacological therapy. A larger RCT with continuous wellness coaching is warranted to more rigorously assess efficacy and optimize protocols.<b>Clinical trial registration:</b> ClinicalTrials.gov, NCT05335850, https://clinicaltrials.gov/study/NCT05335850.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X261463924"},"PeriodicalIF":5.9,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685050","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":"Elevated plasma neurofilament light chain in isolated REM sleep behavior disorder: Associations with neurogenic orthostatic hypotension and implications for phenoconversion.","authors":"Alessandra Calculli, Deborah Di Martino, Piergiorgio Grillo, Gabriele Bellini, Stella Gagliardi, Elena Capriglia, Carlo Fazio, Davide Comolli, Gaetano Malomo, Simone Regalbuto, Michelangelo Maestri, Domeniko Hoxhaj, Enrica Bonanni, Roberto Ceravolo, Silvia Cerri, Antonio Pisani, Michele Terzaghi","doi":"10.1177/1877718X261418988","DOIUrl":"10.1177/1877718X261418988","url":null,"abstract":"<p><p>BackgroundIsolated REM sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Evaluating trajectories of phenoconversion is crucial in this population. Plasma neurofilament light chain (NfL), a marker of axonal injury, has emerged as a promising candidate for tracking disease progression.ObjectivesTo assess plasma NfL levels in iRBD patients, examine their associations with clinical features, particularly neurogenic orthostatic hypotension (nOH), and explore their potential role in predicting phenoconversion.MethodsPlasma NfL was measured in 54 iRBD subjects, 54 PD, 54 healthy controls and 16 MSA. Participants underwent motor, cognitive, and non-motor symptoms assessments. Longitudinal follow-up data have been collected for iRBD subjects. NfL was quantified using the Ella platform; analyses were performed with Prism 9.ResultsNfL levels were significantly higher in iRBD compared to controls and similar to PD. iRBD-nOH⁺ patients had significantly higher NfL than nOH^- counterparts, with values overlapping PD and MSA. nOH was inversely associated with hyposmia, supporting phenotypic divergence. NfL correlated positively with SCOPA-AUT and BDI scores. At follow-up, all four MSA converters had nOH at baseline.ConclusionsPlasma NfL elevation in iRBD supports its role as a marker of early neurodegeneration. Its association with nOH suggests that this autonomic feature may identify a biologically more severe iRBD phenotype, possibly on a trajectory toward MSA. These findings warrant extended longitudinal validation and support the integration of clinical and biological markers, including NfL, for stratifying conversion risk.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"895-903"},"PeriodicalIF":5.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690773","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":"Gastroparesis in Parkinson's disease: Diagnostic and clinical implications for optimizing pharmacological treatment.","authors":"Quentin Damiens, Victor Mille, Justin Faure, Eric Toussirot, Marie-Blanche Valnet-Rabier, Matthieu Béreau","doi":"10.1177/1877718X261432743","DOIUrl":"10.1177/1877718X261432743","url":null,"abstract":"<p><p>Gastroparesis (GP), defined as delayed gastric emptying (GE) without mechanical obstruction, is an underdiagnosed non-motor symptom of Parkinson's disease (PD) that may affect levodopa pharmacokinetics and contribute to motor fluctuations. In PD, GP pathophysiology involves Lewy pathology in the enteric nervous system, neurohormonal dysregulation, gut microbiota alterations, and adverse effects of medications, including levodopa. Disruption of the gut-brain axis further exacerbates gastrointestinal dysmotility, leading to malnutrition, reduced quality of life, and increased hospitalization rates. Clinically, GP delays GE, resulting in erratic levodopa absorption and unpredictable ON/OFF responses. Diagnosis is challenging due to symptom overlap with other gastrointestinal disorders and the lack of validated scales specific to GP in PD. Gastric scintigraphy remains the reference method for assessing GE, although its use is limited by methodological variability and interference from ongoing PD treatments.This review critically examines the epidemiology, pathophysiology, and clinical consequences of GP in PD, and highlights its bidirectional relationship with levodopa pharmacokinetics, particularly its contribution to motor fluctuations. We discuss current pharmacological management strategies, with a focus on the efficacy and safety profile of domperidone. Finally, we propose the hypothesis that the future integration of digestive biomarkers and longitudinal clinical data could contribute to a more individualized treatment approach.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"842-863"},"PeriodicalIF":5.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211516","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}