NPJ Parkinson's Disease最新文献

{"title":"The impact of nocturnal hypokinesia on supervised and unsupervised mobility in people with Parkinson’s disease","authors":"Edoardo Bianchini, Pietro Lombardo, Tracy Milane, Domiziana Rinaldi, Lanfranco De Carolis, Marika Alborghetti, Antonio Suppa, Marco Salvetti, Clint Hansen, Nicolas Vuillerme","doi":"10.1038/s41531-026-01587-2","DOIUrl":"https://doi.org/10.1038/s41531-026-01587-2","url":null,"abstract":"Nocturnal hypokinesia (NH) is a disabling and underrecognized symptom of Parkinson’s disease (PD), affecting nighttime movements and sleep quality. However, its impact on daytime mobility remains unclear. This study investigated supervised and unsupervised mobility in propensity score-matched mild-to-moderate PD patients with (PD NH + ) and without NH (PD NH − ). Eighty-eight participants (44 PD NH+ and 44 PD NH-) underwent clinical assessments, mobility tests (i.e., 20-m forward walking, instrumented Timed-Up-and-Go and 3-metre backward walking test), and 5-day monitoring of average daily steps (AvDS) through a commercial activity tracker (Garmin Vivosmart 4). PD NH+ demonstrated worse functional mobility, reduced turning velocity, slower backwards walking, and fewer AvDS than PD NH-. Furthermore, NH severity correlated negatively with most supervised measures and with AvDS. However, sensitivity analyses controlling for fear of falling attenuated group differences in supervised mobility to non-significance, suggesting a preliminary nature of these findings. The association between NH severity and daily step count showed greater robustness. These findings suggest that NH could be associated with impaired daytime mobility and worse motor function. These findings highlight the importance of targeted interventions to address both nocturnal and diurnal mobility impairments in PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"15 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of novel autoantibodies in Parkinson’s disease using a functional protein array platform","authors":"Yin Xia Chao, Bernett TK Lee, Suh Yee Goh, Muhammad Yaaseen Gulam, Jolene SY Tan, Anis Larbi, Lei Feng, Ee-Wei Lim, Kumar M. Prakash, Louis C. S. Tan, Olaf Rötzschke, Jonathan M. Blackburn, Eng-King Tan","doi":"10.1038/s41531-026-01568-5","DOIUrl":"https://doi.org/10.1038/s41531-026-01568-5","url":null,"abstract":"Autoimmunity has been implicated in Parkinson’s disease (PD), but the role of peripheral autoantibodies is unclear. Using a novel autoantibody screening platform (based on 3D protein structures), a 2-stage case-control study was conducted to identify peripheral autoantibodies in PD. 340 subjects, comprising of 140 age-and-gender-matched participants (50 PD patients and 90 healthy controls (HCs)) in the discovery cohort and a validation cohort involving 200 participants (110 PD patients and 90 HCs) were recruited. A two-pronged analysis approach and gender-corrected analysis identified increased levels of twelve autoantibodies in more PD patients’ plasmas than HCs. A transcriptomic meta-analysis, consisting of 62 datasets, confirmed the dysregulation of these targets in the blood and/or brain of PD patients. STRING analysis revealed that these targets mediate translation regulation and endothelial cell activity and vascular development/angiogenesis. These autoantibodies may be useful as potential diagnostic markers and/or targets for further pathophysiologic and therapeutic studies in PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"13 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resting state fMRI network topographies in preclinical and early Parkinson’s disease stages","authors":"Amgad Droby, Nha Nguyen, Patrick Do, Jack Truong, Barbara Marebwa, Jesse M. Cedarbaum, Anat Mirelman, David Eidelberg, An Vo, Avner Thaler","doi":"10.1038/s41531-026-01584-5","DOIUrl":"https://doi.org/10.1038/s41531-026-01584-5","url":null,"abstract":"Functional brain network disruptions, including PD-related (PDRP) and cognition-related (PDCP) patterns identified by [18F]-FDG PET, occur in Parkinson’s disease (PD). This study assessed whether these patterns are detectable in preclinical and early PD using resting-state fMRI (rs-fMRI) in first-degree non-manifesting carriers (NMCs) of PD-associated mutations (GBA1, LRRK2). We analyzed 295 rs-fMRI datasets from 52 early PD patients, 92 NMCs (47 GBA1, 45 LRRK2), and 58 healthy non-carriers (NMNCs). Using independent component analysis and support vector machine classification, distinguishing PD from NMNCs with 87% accuracy (78% average). Local interpretable model-agnostic explanations isolated fMRI-derived PD-related (fPDRP) and cognition-related (fPDCP) patterns. Expression scores were compared across groups relative to MDS likelihood risk (LR), genetic status, and CSF α-synuclein seed amplification assay (SAA) status and validated in an independent cohort of 33 NMCs followed for ten years. PD patients showed significantly higher fPDRP and fPDCP expression than preclinical groups. Among preclinical individuals, high LR ( ≥ 60) showed elevated fPDRP but unchanged fPDCP. Genetic and CSF SAA status did not significantly affect expression in clinical PD. Patterns were reproducible in the validation cohort. Eight converters showed numerically higher baseline fPDRP than non-converters (ns). These findings support functional network measures as markers of early PD risk and progression.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"23 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prodromal non-motor symptom trajectories preceding Parkinson disease diagnosis: a retrospective matched case-control study using the All of Us Research Program","authors":"Meet Popatbhai Kachhadia, Sameea Husain Wilson, Marc A. Swerdloff, Juber D. Shaikh","doi":"10.1038/s41531-026-01591-6","DOIUrl":"https://doi.org/10.1038/s41531-026-01591-6","url":null,"abstract":"Parkinson disease (PD) is preceded by a prodromal phase characterized by non-motor features and subtle motor changes that may appear years before clinical diagnosis. We conducted a retrospective matched case-control study using the All of Us Registered Tier dataset (Curated Data Repository version R2025Q4R6). Cases required 2 or more distinct PD diagnosis dates and age 40 years or older; each was matched to 4 controls without PD by sex and birth year, and 9 prodromal non-motor features were ascertained from condition records before the index date. Feature concept sets were generated by name-based discovery over standard SNOMED condition concepts with descendant expansion, audited per concept, and are reported in full. Associations were estimated with conditional logistic regression; K-means clustering was applied as an exploratory analysis. The cohort comprised 2673 cases and 10,692 matched controls (mean age 66.8 years; 61.2% male). REM sleep behavior disorder (RBD) showed the strongest association with PD (odds ratio [OR] 9.68; 95% CI 5.89 to 15.90), followed by mild cognitive impairment (MCI) (OR 4.10; 3.09 to 5.46), orthostatic hypotension (OR 1.83; 1.46 to 2.30), constipation (OR 1.30; 1.14 to 1.49), urinary dysfunction (OR 1.27; 1.12 to 1.44), depression (OR 1.23; 1.09 to 1.39), and anxiety (OR 1.19; 1.05 to 1.35). Insomnia was not associated (OR 0.98; 0.85 to 1.12). Erectile dysfunction showed a statistically significant inverse association (OR 0.83; 0.72 to 0.97) that was unstable across sensitivity analyses and is interpreted as differential ascertainment rather than a protective effect. Estimates for RBD, MCI, and orthostatic hypotension were stable across ten sensitivity analyses, including three alternative MCI concept definitions and restriction to levodopa-treated cases; depression and anxiety attenuated to the null under levodopa restriction. Overall discrimination was modest (concordance 0.58; area under the curve 0.585). In this large, diverse US cohort, RBD, MCI, and orthostatic hypotension were the prodromal non-motor features most strongly associated with subsequent PD diagnosis; EHR-documented non-motor features are informative at the group level but limited as individual-level predictors.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"58 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypokinesia and bradykinesia in Parkinson’s disease are consistent with reduced motor vigour, not an impaired capacity to generate and transmit neural drive to muscle","authors":"Vishal Rawji, Cosima Graef, Thomas Foltynie, Shlomi Haar, Yen F. Tai, Mark Edwards, Dario Farina","doi":"10.1038/s41531-026-01590-7","DOIUrl":"https://doi.org/10.1038/s41531-026-01590-7","url":null,"abstract":"Hypokinesia and bradykinesia in Parkinson’s disease have been attributed to reduced motor vigour, an account that assumes the neural drive to muscle is intact but inappropriately scaled; an alternative is that generation of the drive is itself impaired. We recorded high-density surface EMG in 12 people with Parkinson’s disease treated with subthalamic deep brain stimulation and 10 age-matched controls. During ballistic isometric contractions to 10, 30 and 50% of maximum voluntary force, controls usually reached the target with a single burst of motor unit activity (1.41 ± 0.10 bursts), whereas patients used multiple smaller bursts (2.57 ± 0.26), increasing further when stimulation was switched off (2.90 ± 0.30) alongside worsening bradykinesia. Interestingly, the first burst at 30 and 50% was large enough to have achieved the 10 and 30% targets, indicating that patients could, but did not, generate appropriately sized neural drives. Motor unit discharge rate and variability during both ballistic and repetitive contractions did not differ between groups or stimulation conditions, indicating preserved mechanisms to generate and transmit neural drive to muscle. Because successive bursts are separated by delays, patients reached target forces ~ 230 ms later than controls. Slowness therefore reflects underscaled motor commands rather than deficient neural drive, consistent with the motor vigour hypothesis.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"8 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive impairment in Parkinson’s disease: prevalence and associations with cardiometabolic, vascular, and autonomic factors—a systematic review and meta-analysis","authors":"Jiang Wang, Hongshuai Zhou, Tian Tian, Jiayuan Wen, Yutong Wu, Jiahui Bian, Haotian Zhou, Yuchang Liang, Keqin Luo, Huixue Zuo, Zhixuan Zhou, Wenting Zhang, Zhiqi Jiang, Wenshu Chen, Maolin Zou, Jian Liao, Hao Zeng, Yibin Hu, Xiaotao Liang, Xin Jiang, Ziqian Guo, Xiaotong Sun, Muxin Hu, Jiacheng Zhang, Jiayi Zeng, Zuliang Gu, Xiaoming Zhang","doi":"10.1038/s41531-026-01573-8","DOIUrl":"https://doi.org/10.1038/s41531-026-01573-8","url":null,"abstract":"Cognitive impairment is a common and disabling non-motor manifestation of Parkinson’s disease (PD), but its prevalence and associated factors remain unclear. This systematic review and meta-analysis aimed to estimate the pooled prevalence of cognitive impairment in PD and identify associated clinical factors. We searched electronic databases for observational studies and performed random-effects meta-analyses with subgroup analyses, sensitivity analyses, publication bias assessment, and GRADE evaluation. Fifty-five studies involving 103,145 participants were included. The pooled prevalence of cognitive impairment was 32.7% (95% CI: 27.1–38.7%), with substantial heterogeneity (I² = 97.7%). Prevalence varied according to diagnostic criteria and assessment tools. Orthostatic hypotension (OR = 2.18, 95% CI:1.71–2.77) and advanced age were strongly associated with cognitive impairment, while diabetes, hypertension, and metabolic syndrome showed additional associations. Evidence certainty ranged from low to very low. Cognitive impairment affects approximately one-third of individuals with PD, highlighting the need for early screening and longitudinal research.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"23 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional pathway phenotyping reveals increased LRRK2 activity beyond recognised genetic causes of Parkinson’s disease","authors":"Neringa Pratuseviciute,Walter Pirker,Jennifer Huber,Sara Gomes,Iolo Squires,Renata Filipe Soares,Christof Brücke,Alexander Zimprich,Esther Sammler","doi":"10.1038/s41531-026-01575-6","DOIUrl":"https://doi.org/10.1038/s41531-026-01575-6","url":null,"abstract":"Abstract Pathogenic LRRK2 variants cause Parkinson’s disease (PD) through increased kinase activity, with VPS35 p.D620N and other emerging genetic factors also increasing LRRK2 signalling. Findings in idiopathic PD also suggest broader LRRK2 pathway involvement. As LRRK2-targeted therapies advance, identifying patients with elevated LRRK2 kinase activity beyond known mutations is essential. Here, we quantified LRRK2-dependent Rab10 phosphorylation at threonine 73 in blood neutrophils from 181 genetically enriched PD patients and 71 controls. Whole-exome sequencing identified pathogenic and rare variants. VPS35 p.D620N carriers showed marked LRRK2 pathway activation, defining a biological reference threshold. Fourteen percent of PD patients without recognised pathogenic variants exhibited similar or greater pathway activation. In a subset of PD patients with increased LRRK2 pathway activity, genes harbouring rare variants were selected for exploratory functional assessment using siRNA knockdown in A549 cells. The screen identified several candidate genetic modifiers of LRRK2 signalling, including NECAP2. Overall, functional assessment of LRRK2 pathway activity identified a subset of PD patients with convergent pathway activation despite the absence of recognised pathogenic variants, supporting the integration of functional pathway phenotyping with genomic analysis for patient stratification.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"18 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149049069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-year smartphone motor monitoring in isolated REM sleep behavior disorder and Parkinson’s disease","authors":"Vojtěch Illner,Michal Novotný,Tomáš Kouba,Tereza Tykalová,Michal Šimek,Martin Šubert,Pavel Sovka,Jan Švihlík,Evžen Růžička,Karel Šonka,Petr Dušek,Jan Rusz","doi":"10.1038/s41531-026-01588-1","DOIUrl":"https://doi.org/10.1038/s41531-026-01588-1","url":null,"abstract":"Abstract We aimed to assess the sensitivity of key motor smartphone tasks to detect disease progression in subjects with isolated rapid eye movement sleep behavior disorder (iRBD) and early Parkinson’s disease (PD) compared to healthy controls. Twenty-six healthy controls, 22 patients with iRBD and 23 patients with early-stage PD performed speech, psychomotor, hand tremor, and U-turn tasks using a smartphone every 14 days for 24 months. Disease progression in iRBD was observed through monopitch during reading and slowing turn speed (both p  < 0.05), whereas in PD, shortening of time to first voice break during phonation ( p  < 0.05). Several speech, psychomotor, and U-turn measures showed adequate cross-sectional sensitivity to distinguish iRBD or PD from controls. Significant learning effect in the first year influenced measures derived from oral diadochokinesis, tapping, and hand tremor. This study represents guidance for future remote smartphone trials that integrate diverse motor domains to monitor prodromal and early Parkinsonism.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"101 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149049070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data from the ROPAD study corroborate an association between ITSN1 loss-of-function variants and Parkinson’s disease","authors":"Christian A. Ganoza,Ana Westenberger,Jefri J. Paul,Filipa Curado,Emma N. Somerville,Jörg Rennecke,Peter Bauer,Christian Beetz","doi":"10.1038/s41531-026-01562-x","DOIUrl":"https://doi.org/10.1038/s41531-026-01562-x","url":null,"abstract":"","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"479 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149049073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: Data from the ROPAD study corroborate an association between ITSN1 loss-of-function variants and Parkinson’s disease","authors":"Guillaume Cogan,Christelle Tesson,Lisa Welment,Fabienne Clot,Eric LeGuern,Aymeric Lanore,Alexandra Dürr,Florence Cormier-Dequaire,Bérengère Debilly,Marc Planes,Graziella Mangone,Suzanne Lesage,Alexis Brice","doi":"10.1038/s41531-026-01470-0","DOIUrl":"https://doi.org/10.1038/s41531-026-01470-0","url":null,"abstract":"","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"5 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149049071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}