Journal of Neurology最新文献

{"title":"Effects of psychological therapies in people with multiple sclerosis: a systematic review and network meta-analysis of randomized controlled trials.","authors":"Jillian Scandiffio, Laura Kathleen Langer, Vjura Senthilnathan, Gregory Feng, Ashvene Sureshkumar, Michelle Bromberg, Jessica Babineau, Sarah J Donkers, Katherine B Knox, Tania Bruno, Lisa A S Walker, Mark Theodore Bayley, Robert Simpson","doi":"10.1007/s00415-025-13315-6","DOIUrl":"10.1007/s00415-025-13315-6","url":null,"abstract":"<p><strong>Background: </strong>People with MS (PwMS) often experience high levels of emotional distress. Interventions to improve emotional wellbeing in PwMS are needed; however, the effectiveness of diverse psychological therapies in PwMS on cumulative outcomes is not well understood. This systematic review and network meta-analysis (NMA) aims to evaluate the effectiveness of psychological therapies in PwMS.</p><p><strong>Methods: </strong>Five databases were searched (CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE ALL, APA PsycINFO) from 1984 to April 2025. Randomized controlled trials that compared a psychological intervention with any comparator in PwMS were included. Two independent reviewers performed data extraction and risk of bias analysis. A standard random-effects Bayesian consistency NMA was fitted. Outcome domains included mental health, cognition, physical health, quality of life (QoL), and health economics.</p><p><strong>Results: </strong>After screening, 111 studies were included in the review, 89 included in the meta-analysis, and 77 included in the NMA (n = 3911 participants). Cognitive behavioural therapy was found to be most effective in improving outcomes overall, with the greatest changes in mean difference (MD 11.0, 95% CI 5.72-16.2) when compared with control conditions. Psychological therapies significantly improved mental health outcomes (SMD 1.41; 95% CI 1.00-1.83; p < 0.00001), physical health outcomes (SMD 1.08; 95% CI 0.41-1.74; p < 0.00001), QoL (SMD 0.77; 95% CI 0.21-1.34), and cognition (SMD 0.66, 95% CI 0.24-1.07) in PwMS.</p><p><strong>Conclusions: </strong>This systematic review and NMA found that psychological interventions are broadly effective in PwMS across mental health, cognitive, physical and QoL outcome domains, and provides strong support for their use in the care of PwMS.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"584"},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stratify and ImmunoWELL JCV tests performances in a real-world multiple sclerosis cohort: possible clinical implications of biosimilar Natalizumab use.","authors":"Simone Guerrieri, Irene Gattuso, Angela Genchi, Agostino Nozzolillo, Vittorio Viti, Chiara Zanetta, Giulia D'Amore, Maria A Rocca, Lucia Moiola, Massimo Filippi","doi":"10.1007/s00415-025-13273-z","DOIUrl":"10.1007/s00415-025-13273-z","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"583"},"PeriodicalIF":4.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First the B cells fall, then the T cells follow: temporal immunological shift with ocrelizumab in multiple sclerosis.","authors":"Gianmarco Abbadessa, Elisabetta Maida, Simona Bonavita, Luigi Lavorgna","doi":"10.1007/s00415-025-13297-5","DOIUrl":"10.1007/s00415-025-13297-5","url":null,"abstract":"<p><strong>Background: </strong>Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for multiple sclerosis (MS). While its efficacy has been attributed to early and sustained B cell depletion, emerging evidence suggests a broader immunomodulatory profile.</p><p><strong>Objectives: </strong>To investigate temporal dynamics of OCR-induced immune modulation in MS by analyzing pathway enrichment score changes in transcriptomic data from peripheral blood mononuclear cells (PBMCs) at early (2 weeks) and late (6 months) timepoints following treatment initiation.</p><p><strong>Methods: </strong>We analyzed publicly available microarray data (GSE228330) from PBMCs of 15 MS patients treated with OCR. Immune cell subpopulations were estimated using CIBERSORTx with the LM22 signature matrix. Gene Set Variation Analysis (GSVA) was applied to quantify immune-related pathway enrichment across three timepoints-baseline, 2 weeks, and 6 months.</p><p><strong>Results: </strong>Early effects were characterized by selective suppression of B cell-related pathways, including antigen presentation via MHC-II, B cell proliferation, and survival. These changes were accompanied by compensatory upregulation of anti-inflammatory and innate immune signaling (e.g., IL-10, monocyte chemotaxis). At 6 months, B cell pathway suppression persisted and deepened, while T cell-specific pathways (e.g., CD4+ T-cell activation and cytokine production) showed significant downregulation, indicating a delayed but substantial impact on adaptive cellular immunity. At 6 months, T reg compartment was reconfigured, with overall T reg transcription enhanced versus T effector cells, quiescent and thymic‑mature signatures reduced, and IL‑4-induced T reg program enriched.</p><p><strong>Conclusions: </strong>OCR exerts a biphasic immunomodulatory effect, with rapid direct suppression of B cell pathways followed by delayed indirect modulation of T cell-mediated immunity.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"582"},"PeriodicalIF":4.6,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of avalglucosidase alfa in patients with late-onset Pompe disease after 145 weeks of treatment during the COMET trial.","authors":"Priya S Kishnani, Jordi Díaz-Manera, Sergey Illarioshkin, Ans T van der Ploeg, Paula R Clemens, John W Day, Antonio Toscano, Hani Kushlaf, Shafeeq Ladha, Shahram Attarian, Gerson Carvalho, Anna Kostera-Pruszczyk, Sevim Erdem-Özdamar, Ozlem Goker-Alpan, Tahseen Mozaffar, Volker Straub, Mark Roberts, Kristina An Haack, Olivier Huynh-Ba, Swathi Tammireddy, Magali Periquet, Nathan Thibault, Tianyue Zhou, Mazen M Dimachkie, Benedikt Schoser","doi":"10.1007/s00415-025-13266-y","DOIUrl":"10.1007/s00415-025-13266-y","url":null,"abstract":"<p><strong>Background and objectives: </strong>In the COMET trial, avalglucosidase alfa treatment for late-onset Pompe disease was safe, tolerable and associated with stabilization or improvement in disease parameters through 97 weeks. We report outcomes in the trial extension through 145 weeks of treatment.</p><p><strong>Methods: </strong>In this phase 3, double-blind, randomized trial, participants with previously untreated late-onset Pompe disease were randomly assigned to receive 20 mg/kg avalglucosidase alfa or alglucosidase alfa every other week for 49 weeks; thereafter, all patients received 20 mg/kg avalglucosidase alfa every other week. For this analysis, efficacy was assessed at 145 weeks and safety to last follow-up (data cutoff: March 11, 2022).</p><p><strong>Results: </strong>Of 100 participants in the double-blind treatment period, 95 entered the open-label extension, and 88 completed ≥ 145 weeks of treatment. At study start, the mean upright FVC percent predicted was similar between treatment arms, and 6MWT distance was greater in the avalglucosidase alfa arm. From baseline to week 145, the LS mean (SE) FVC percent predicted increased by 1.38 (1.22) in the avalglucosidase alfa arm and 1.25 (1.34) in the switch arm. The LS mean (SE) 6MWT distance walked increased by 20.65 (9.60) m and 0.29 (10.42) m, respectively. Potentially treatment-related adverse events were reported in 27 patients (53%) in the avalglucosidase alfa arm and 25 patients (57%) in the switch arm. Anti-drug antibodies declined over time in both arms.</p><p><strong>Conclusions: </strong>In this randomized clinical trial extension, positive clinical outcomes were maintained for patients taking avalglucosidase alfa for up to 145 weeks with no new safety concerns.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT02782741, https://clinicaltrials.gov/ct2/show/NCT02782741 . Registration date: 2016-05-23; Date of first patient enrolled: 2016-11-02.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"581"},"PeriodicalIF":4.6,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal quantitative analysis guides precise preoperative localization of epilepsy.","authors":"Yuanzhong Shen, Zijian Shen, Yimin Huang, Zhuojin Wu, Yixuan Ma, Feng Hu, Kai Shu","doi":"10.1007/s00415-025-13324-5","DOIUrl":"10.1007/s00415-025-13324-5","url":null,"abstract":"<p><p>Epilepsy surgery efficacy is critically contingent upon the precise localization of the epileptogenic zone (EZ). However, conventional qualitative methods face challenges in achieving accurate localization, integrating multimodal data, and accounting for variations in clinical expertise among practitioners. With the rapid advancement of artificial intelligence and computing power, multimodal quantitative analysis has emerged as a pivotal approach for EZ localization. Nonetheless, no research team has thus far provided a systematic elaboration of this concept. This narrative review synthesizes recent advancements across four key dimensions: (1) seizure semiology quantification using deep learning and computer vision to analyze behavioral patterns; (2) structural neuroimaging leveraging high-field MRI, radiomics, and AI; (3) functional imaging integrating EEG-fMRI dynamics and PET biomarkers; and (4) electrophysiological quantification encompassing source localization, intracranial EEG, and network modeling. The convergence of these complementary approaches enables comprehensive characterization of epileptogenic networks across behavioral, structural, functional, and electrophysiological domains. Despite these advancements, clinical heterogeneity, limitations in algorithmic generalizability, and barriers to data sharing hinder translation into clinical practice. Future directions emphasize personalized modeling, federated learning, and cross-modal standardization to advance data-driven localization. This integrated paradigm holds promise for overcoming qualitative limitations, reducing medical costs, and improving seizure-free outcomes.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"579"},"PeriodicalIF":4.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI-based human brain atlases of R1, R2, proton density, and myelin volume fraction using synthetic quantitative imaging at 1.5 T.","authors":"Hasan Sbaihat, Katharina Roenneke, Dajana Müller, Theodoros Ladopoulos, Ruth Schneider, Britta Krieger, Barbara Bellenberg, Carsten Lukas","doi":"10.1007/s00415-025-13317-4","DOIUrl":"10.1007/s00415-025-13317-4","url":null,"abstract":"<p><p>Quantitative MRI (qMRI) enables objective, reproducible measurement of tissue-specific MR properties, offering improved diagnostic accuracy and deeper insight into disease mechanisms compared to conventional MRI. Parameters such as proton density (PD), relaxation rates (R1, R2), and myelin volume fraction (MVF) provide valuable information on tissue composition, water content, and myelination. Reference qMRI atlases based on these parameters are essential for identifying deviations in individuals and supporting clinical decision-making. While several reference atlases exist, none offer comprehensive, multi-parametric data derived from a single acquisition dataset. In this study, we constructed four synthetic 3D reference brain atlases (isotropic resolution 1.5 mm) of PD, R1, R2, and MVF using the clinically integrated multi-dynamic multi-echo sequence at 1.5 Tesla based on 58 healthy controls (HC). These atlases allow both visual and quantitative comparisons with individual patient data and will be made available to the research community. We validated the atlases using data from four HC and four multiple sclerosis (MS) patients, analyzing both white and gray matter regions. The atlases showed high anatomical accuracy, spatial resolution, and full brain coverage. Significant deviations were observed in MS patients compared to the reference dataset (p < 0.01), while a testing group of HCs closely matched the atlas values. Z-score maps accurately captured lesion patterns and diffuse abnormalities in an individual patient with MS, reflecting early demyelination and tissue damage. These findings demonstrate the clinical potential of our atlases for detecting subtle brain changes.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"578"},"PeriodicalIF":4.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving conscientiousness through a smartphone app and telecoaching intervention: insights from multiple sclerosis and healthy aging samples.","authors":"Michael Jaworski, Jacob Balconi, Celeste Santivasci, Margaret Youngs, Morgan Woodbeck, Nathan Zak, Sara Cruz, Bianca Weinstock-Guttman, Ralph H B Benedict","doi":"10.1007/s00415-025-13320-9","DOIUrl":"10.1007/s00415-025-13320-9","url":null,"abstract":"<p><p>Lower Conscientiousness is associated with cognitive decline, unemployment, and poorer health outcomes in both neurological and aging populations. This study evaluated a smartphone-based intervention to enhance Conscientiousness in people with multiple sclerosis (PwMS) and healthy aging (HA) adults. Initially, 38 PwMS and 22 HA participants completed baseline assessments (cognitive, personality, depression, and anxiety measures). Attrition and disease factors left 24 PwMS and 20 HA adults at the 12-week follow-up. Participants randomly assigned to the intervention arm received the \"Conscientiousness Coach\" app, which combined value identification, SMART goal development, smartphone-based tracking, and scheduled telehealth coaching sessions, whereas controls were wait-listed. ANCOVA for baseline scores showed a significant treatment effect on NEO-FFI Conscientiousness (p = 0.015) that remained after substituting age for diagnosis (p = 0.029). A lack of significant effects for group (PwMS vs. HA) and age indicated that treatment impact was consistent across both samples. Within the intervention group, paired-sample t-tests revealed large gains in the Conscientiousness domain (d = 0.93, p < 0.001) and moderate improvements in the Orderliness (d = 0.67, p = 0.007) and Dependability (d = 0.52, p = 0.030) facets, with no change in wait-list controls. No treatment effects emerged for Neuroticism, depression, or anxiety, underscoring the trait-specific nature of the intervention. Results suggest that targeted digital interventions can favorably impact personality and enhance quality of life. Future study will examine use of AI to replace the behavioral coaching component of this intervention and its long-term impact on personality.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"580"},"PeriodicalIF":4.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of expanded Thrombolysis in Cerebral Infarction (eTICI) grades on clinical outcomes in patients with large ischemic strokes receiving endovascular treatment.","authors":"Miao Chai, Qin Wan, Linyu Li, Wei Chen, Haoxuan Zhu, Jifei Liu, Jie Yang, Guojian Liu, Changwei Guo, Jinfu Ma, Dahong Yang, Zhenxuan Tian, Boyu Chen, Chawen Ding, Xiaolei Shi, Shihai Yang, Jiaxing Song, Zhuang Li, Zhenchang Zhang","doi":"10.1007/s00415-025-13327-2","DOIUrl":"10.1007/s00415-025-13327-2","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the impact of the expanded Thrombolysis in Cerebral Infarction (eTICI) grades on clinical outcomes after endovascular treatment (EVT) for large ischemic strokes.</p><p><strong>Methods: </strong>This study was a substudy of a prospective nationwide multicenter registry that included 490 patients with large ischemic strokes undergoing EVT. The primary outcome was a 90-day modified Rankin Scale (mRS) score of 0-3. Secondary outcomes included the distribution of mRS score, and mRS scores of 0-2 and 0-4 at 90 days. Safety outcomes included 90-day mortality and symptomatic intracranial hemorrhage (sICH) within 48 h.</p><p><strong>Results: </strong>Among 490 patients treated with EVT, 67 (13.7%), 125 (25.5%), and 298 (60.8%) achieved eTICI grades 0-2a, 2b, and 2c-3, respectively. Compared with eTICI grades 0-2a, eTICI grade 2b showed no significant association with an mRS score of 0-3, while eTICI grades 2c-3 were significantly associated with higher odds of achieving an mRS score of 0-3 (adjusted odds ratios [aOR] 3.04, 95% CI 1.39-6.62). Mortality was lower for eTICI grades 2c-3 than for grades 0-2a (aOR 0.47, 95% CI 0.25-0.89). There were no significant differences in sICH rates among three groups. The predicted probability of an mRS score of 0-3 progressively decreased with increasing procedure time, while the predicted probability of mortality progressively increased.</p><p><strong>Conclusion: </strong>In patients with large ischemic strokes undergoing EVT, eTICI grades 2c-3 were significantly associated with improved clinical outcomes. This study suggests that eTICI grades 2c-3 should be considered the ideal target for successful reperfusion in this patient population.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"577"},"PeriodicalIF":4.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing human versus artificial intelligence for health literacy among patients with neurological disorders (HANDs study).","authors":"Carolina Soares, Carolina Correia, Rita Nunes Rato, Manuel Gonçalves-Pinho, Alessandro Zampogna, Andreia Costa","doi":"10.1007/s00415-025-13305-8","DOIUrl":"10.1007/s00415-025-13305-8","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"575"},"PeriodicalIF":4.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSF phospho-tau levels at Parkinson's disease onset predict the risk for development of motor complications.","authors":"Jacopo Bissacco, Giulia Di Lazzaro, Roberta Bovenzi, Giulia Maria Sancesario, Matteo Conti, Clara Simonetta, Davide Mascioli, Maria Mancini, Veronica Buttarazzi, Mariangela Pierantozzi, Massimo Pieri, Sergio Bernardini, Alessandro Stefani, Anna Rita Bentivoglio, Paolo Calabresi, Nicola Biagio Mercuri, Tommaso Schirinzi","doi":"10.1007/s00415-025-13325-4","DOIUrl":"10.1007/s00415-025-13325-4","url":null,"abstract":"<p><strong>Background: </strong>Motor complications (MC), including fluctuations, represent a disabling milestone of Parkinson's disease (PD) course, although the underlying early pathophysiological mechanisms remain unclear. We therefore investigated whether the biological profile at PD onset, as defined through a panel of CSF biomarkers, may predispose to the development of MC.</p><p><strong>Methods: </strong>We conducted a dual-center retrospective longitudinal study involving 131 de novo (DN) PD patients (newly diagnosed, untreated). At baseline, patients were evaluated by motor and non-motor scores, and the measurement of CSF total α-synuclein (α-syn), total and phosphorylated-181-tau (t-tau, p-tau), amyloid-β42 and amyloid-β40 (Aβ42, Aβ40) levels, p-tau/t-tau, Aβ42/Aβ40, and p-tau/Aβ42 ratios. According to the successive development of MC, patients were classified as \"with MC\" (wMC) or \"without MC\" (noMC). A control group of 107 controls was also collected. Variables were compared between groups, adjusting for main covariates; ROC and Cox analyses evaluated predictive values.</p><p><strong>Results: </strong>The DN PD cohort was followed for 57 (± 18) months, with 38 (29%) patients developing MC. At baseline, DN patients showed lower CSF total α-syn and t-tau levels than controls. The wMC group had higher p-tau, p-tau/t-tau, and p-tau/Aβ42 ratios than noMC. The p-tau/t-tau ratio best predicted MC development; above the cutoff of 0.148, MC were 2.6 times more likely with 81% sensitivity and 61% specificity (AUC = 0.79).</p><p><strong>Conclusions: </strong>Elevated CSF p-tau/t-tau ratio in DN PD patients predicts higher MC risk, supporting biomarker-based stratification for patients at onset. Our findings also highlight Alzheimer's co-pathology, especially tauopathy, as a key factor in shaping PD motor progression from early stages.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"573"},"PeriodicalIF":4.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}