Pub Date : 2025-12-01DOI: 10.1001/jamaneurol.2025.4721
Michael Malek-Ahmadi,Savar Sharma,Fawaz Stipho,Marisa Denkinger,Alpana Singh,Wagner S Brum,Nicholas J Ashton
ImportanceBlood-based biomarkers (BBMs) demonstrate high accuracy in detecting Alzheimer disease (AD) pathological changes in symptomatic individuals. In autosomal dominant AD and in individuals with Down syndrome, both populations with near-universal development of AD pathology, elevations in BBMs are detectable years before clinical onset, supporting their utility for identifying preclinical disease in these cases. Among BBMs, plasma phosphorylated tau 217 (p-tau217) exhibits strong concordance with established in vivo markers of AD pathology. However, its ability to identify older adults without cognitive impairment who are amyloid-positive remains variable across studies and settings.ObjectiveTo assess the standardized effect size of mean differences and classification accuracy of p-tau217 for published studies that compared amyloid-positive and amyloid-negative older adults without cognitive impairment.Data SourcesPubMed, Embase, and EBSCOhost databases from inception to September 1, 2025.Study SelectionObservational studies or randomized clinical trials with baseline data on individuals without cognitive impairment who were classified as either amyloid positive or amyloid negative and reported numeric data for p-tau217 levels.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guideline was used for this study. Two authors independently carried out literature searches to identify studies with older adults without cognitive impairment who were classified as either amyloid positive or amyloid negative where p-tau217 was quantified.Main Outcome and MeasureThe standardized mean difference (Hedges g) was used to characterize differences in mean p-tau217 levels. A pooled area under the curve (AUC) value was used to summarize the diagnostic accuracy of p-tau217 in identifying amyloid-positive individuals. Between-study heterogeneity was investigated using subgroup and sensitivity analyses. Publication bias was assessed using Egger tests.ResultsData for 7834 participants (2533 amyloid positive, 5301 amyloid negative) from 18 publications were analyzed. A large effect size was observed for p-tau217 (Hedges g = 1.50; 95% CI, 1.33-1.68). Values for p-tau217 also demonstrated high accuracy for identifying amyloid-positive individuals without cognitive impairment (AUC = 0.87; 95% CI, 0.85-0.90).Conclusion and RelevanceThese findings demonstrate that plasma p-tau217 can reliably detect AD pathology in the preclinical stage. These findings support the clinical utility of plasma p-tau217 as a scalable, minimally invasive tool for early identification of AD, particularly in settings where timely intervention with disease-modifying therapies may offer the greatest benefit in slowing or preventing disease progression.
{"title":"Plasma Phosphorylated Tau 217 and Amyloid Burden in Older Adults Without Cognitive Impairment: A Meta-Analysis.","authors":"Michael Malek-Ahmadi,Savar Sharma,Fawaz Stipho,Marisa Denkinger,Alpana Singh,Wagner S Brum,Nicholas J Ashton","doi":"10.1001/jamaneurol.2025.4721","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4721","url":null,"abstract":"ImportanceBlood-based biomarkers (BBMs) demonstrate high accuracy in detecting Alzheimer disease (AD) pathological changes in symptomatic individuals. In autosomal dominant AD and in individuals with Down syndrome, both populations with near-universal development of AD pathology, elevations in BBMs are detectable years before clinical onset, supporting their utility for identifying preclinical disease in these cases. Among BBMs, plasma phosphorylated tau 217 (p-tau217) exhibits strong concordance with established in vivo markers of AD pathology. However, its ability to identify older adults without cognitive impairment who are amyloid-positive remains variable across studies and settings.ObjectiveTo assess the standardized effect size of mean differences and classification accuracy of p-tau217 for published studies that compared amyloid-positive and amyloid-negative older adults without cognitive impairment.Data SourcesPubMed, Embase, and EBSCOhost databases from inception to September 1, 2025.Study SelectionObservational studies or randomized clinical trials with baseline data on individuals without cognitive impairment who were classified as either amyloid positive or amyloid negative and reported numeric data for p-tau217 levels.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guideline was used for this study. Two authors independently carried out literature searches to identify studies with older adults without cognitive impairment who were classified as either amyloid positive or amyloid negative where p-tau217 was quantified.Main Outcome and MeasureThe standardized mean difference (Hedges g) was used to characterize differences in mean p-tau217 levels. A pooled area under the curve (AUC) value was used to summarize the diagnostic accuracy of p-tau217 in identifying amyloid-positive individuals. Between-study heterogeneity was investigated using subgroup and sensitivity analyses. Publication bias was assessed using Egger tests.ResultsData for 7834 participants (2533 amyloid positive, 5301 amyloid negative) from 18 publications were analyzed. A large effect size was observed for p-tau217 (Hedges g = 1.50; 95% CI, 1.33-1.68). Values for p-tau217 also demonstrated high accuracy for identifying amyloid-positive individuals without cognitive impairment (AUC = 0.87; 95% CI, 0.85-0.90).Conclusion and RelevanceThese findings demonstrate that plasma p-tau217 can reliably detect AD pathology in the preclinical stage. These findings support the clinical utility of plasma p-tau217 as a scalable, minimally invasive tool for early identification of AD, particularly in settings where timely intervention with disease-modifying therapies may offer the greatest benefit in slowing or preventing disease progression.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"149 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145644885","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}
Pub Date : 2025-12-01DOI: 10.1001/jamaneurol.2025.4712
Pierre Seners,Nour Nehme,Adrien Ter Schiphorst,Frédérique Charbonneau,Nicolas Chausson,Marie Belley,Anne Wacongne,Olfa Kaaouana,Carole Henry,Andrei Girbovan,Omar Naciri Bennani,Benjamin Maïer,Mathilde Dupin,Gaspard Gerschenfeld,François Lun,Guillaume Marc,Jérémie Dassa,Tristan Benoit,Denis Sablot,Julia Loeillot,Julien Rigal,Didier Smadja,Luca Scarcia,Jildaz Caroff,Fernando Pico,Hilde Henon,Stéphane Skerlak,Florian Basille,Wagih Ben Hassen,Gaultier Marnat,Julien Allard,Loïc Legris,Romain Bourcier,Géraud Forestier,Cyril Chivot,Gregory W Albers,Maarten G Lansberg,Guillaume Turc,Jérémie Papassin,
ImportanceIn patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO), the benefit of intravenous thrombolysis (IVT) administered beyond 4.5 hours from the last time known well before endovascular therapy (EVT) is uncertain. Recently, the TIMELESS trial failed to demonstrate a benefit of IVT in this setting, but this trial focused on patients directly admitted to comprehensive stroke centers (CSCs) with fast access to EVT.ObjectiveTo assess the efficacy and safety of IVT initiated beyond 4.5 hours in patients with AIS-LVO initially admitted to primary stroke centers (PSCs) and subsequently transferred to a CSC for EVT, allowing substantial time for the IVT to take effect.Design, Setting, and ParticipantsThis multicenter retrospective cohort study was conducted between January 2020 and December 2024, with 3-month follow-up, at 20 French PSCs. All consecutive patients with AIS-LVO admitted beyond 4.5 hours from the last time they were known well in the PSC and subsequently transferred to a CSC for EVT, with or without IVT administered prior to transfer, were eligible for inclusion. Data analysis was performed between May 2025 and July 2025.Main Outcomes and MeasuresThe primary outcome was the 3-month modified Rankin Scale score, analyzed in the ordinal approach. Propensity score with overlap weighting (PSOW) balanced covariates between patients treated with IVT vs those without.ResultsA total of 584 patients were included, among whom 309 patients (52.9%) were female. Median (IQR) age was 71 (61-81) years, median (IQR) baseline National Institutes of Health Stroke scale score was 15 (10-19), median (IQR) time from last known well to PSC imaging was 10.5 (6.9-14.0) hours, and 232 patients (39.7%) received IVT before transfer. Advanced brain imaging (magnetic resonance imaging or computed tomography [CT] with CT-perfusion) was performed at the PSC in 544 patients (93.2%). IVT use before transfer was independently associated with a shift toward better 3-month outcomes (PSOW-common odds ratio [OR], 1.97; 95% CI, 1.33-2.92; P = .001) and higher odds of recanalization during transfer (PSOW-OR, 8.69; 95% CI, 3.16-23.87; P < .001) compared with those without. The rate of any intracerebral hemorrhage and symptomatic intracerebral hemorrhage were similar between groups.Conclusions and RelevanceIn this multicenter cohort study, IVT initiated beyond 4.5 hours prior to interhospital transfer for EVT was associated with higher rates of recanalization during transfer and improved 3-month functional outcomes, without safety concerns. These findings offer encouraging support for clinical trials evaluating IVT in the late time window before interhospital transfer.
在因大血管闭塞（AIS-LVO）引起的急性缺血性卒中患者中，距血管内治疗（EVT）的最后已知时间超过4.5小时的静脉溶栓（IVT）治疗的益处尚不确定。最近，TIMELESS试验未能证明IVT在这种情况下的益处，但该试验的重点是直接入住综合卒中中心（CSCs）的患者，他们可以快速获得EVT。目的评估最初入住初级卒中中心（PSCs）并随后转移到CSC进行EVT的AIS-LVO患者超过4.5小时开始IVT的有效性和安全性，从而使IVT有足够的时间发挥作用。设计、环境和参与者本多中心回顾性队列研究于2020年1月至2024年12月在20个法国psc进行了为期3个月的随访。所有连续的AIS-LVO患者，从他们最后一次在PSC中已知的时间起超过4.5小时，随后转移到CSC进行EVT，转移前是否给予IVT，都符合纳入条件。数据分析时间为2025年5月至2025年7月。主要结局和测量主要结局为3个月的修正Rankin量表评分，采用顺序方法进行分析。使用重叠加权（PSOW）的倾向评分平衡了接受IVT治疗与未接受IVT治疗的患者之间的协变量。结果共纳入584例患者，其中女性309例，占52.9%。中位（IQR）年龄为71（61-81）岁，中位（IQR）基线美国国立卫生研究院卒中量表评分为15(10-19)，中位（IQR）时间为10.5（6.9-14.0）小时，232例（39.7%）患者在转院前接受了IVT。544例（93.2%）患者在PSC处进行了高级脑成像（磁共振成像或CT灌注）。移植前使用IVT与向更好的3个月预后转移独立相关(pso -common比值比[OR]， 1.97; 95% CI, 1.33-2.92; P =。PSOW-OR, 8.69; 95% CI, 3.16-23.87; P < 0.05。001)。两组间脑出血发生率及症状性脑出血发生率相似。结论和相关性在这项多中心队列研究中，在EVT转院前超过4.5小时开始的IVT与转院期间更高的再通率和改善的3个月功能结果相关，没有安全性问题。这些发现为临床试验在医院间转院前评估IVT提供了令人鼓舞的支持。
{"title":"Intravenous Thrombolysis Use in the Late Time Window Before Interhospital Transfer for Thrombectomy.","authors":"Pierre Seners,Nour Nehme,Adrien Ter Schiphorst,Frédérique Charbonneau,Nicolas Chausson,Marie Belley,Anne Wacongne,Olfa Kaaouana,Carole Henry,Andrei Girbovan,Omar Naciri Bennani,Benjamin Maïer,Mathilde Dupin,Gaspard Gerschenfeld,François Lun,Guillaume Marc,Jérémie Dassa,Tristan Benoit,Denis Sablot,Julia Loeillot,Julien Rigal,Didier Smadja,Luca Scarcia,Jildaz Caroff,Fernando Pico,Hilde Henon,Stéphane Skerlak,Florian Basille,Wagih Ben Hassen,Gaultier Marnat,Julien Allard,Loïc Legris,Romain Bourcier,Géraud Forestier,Cyril Chivot,Gregory W Albers,Maarten G Lansberg,Guillaume Turc,Jérémie Papassin, ","doi":"10.1001/jamaneurol.2025.4712","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4712","url":null,"abstract":"ImportanceIn patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO), the benefit of intravenous thrombolysis (IVT) administered beyond 4.5 hours from the last time known well before endovascular therapy (EVT) is uncertain. Recently, the TIMELESS trial failed to demonstrate a benefit of IVT in this setting, but this trial focused on patients directly admitted to comprehensive stroke centers (CSCs) with fast access to EVT.ObjectiveTo assess the efficacy and safety of IVT initiated beyond 4.5 hours in patients with AIS-LVO initially admitted to primary stroke centers (PSCs) and subsequently transferred to a CSC for EVT, allowing substantial time for the IVT to take effect.Design, Setting, and ParticipantsThis multicenter retrospective cohort study was conducted between January 2020 and December 2024, with 3-month follow-up, at 20 French PSCs. All consecutive patients with AIS-LVO admitted beyond 4.5 hours from the last time they were known well in the PSC and subsequently transferred to a CSC for EVT, with or without IVT administered prior to transfer, were eligible for inclusion. Data analysis was performed between May 2025 and July 2025.Main Outcomes and MeasuresThe primary outcome was the 3-month modified Rankin Scale score, analyzed in the ordinal approach. Propensity score with overlap weighting (PSOW) balanced covariates between patients treated with IVT vs those without.ResultsA total of 584 patients were included, among whom 309 patients (52.9%) were female. Median (IQR) age was 71 (61-81) years, median (IQR) baseline National Institutes of Health Stroke scale score was 15 (10-19), median (IQR) time from last known well to PSC imaging was 10.5 (6.9-14.0) hours, and 232 patients (39.7%) received IVT before transfer. Advanced brain imaging (magnetic resonance imaging or computed tomography [CT] with CT-perfusion) was performed at the PSC in 544 patients (93.2%). IVT use before transfer was independently associated with a shift toward better 3-month outcomes (PSOW-common odds ratio [OR], 1.97; 95% CI, 1.33-2.92; P = .001) and higher odds of recanalization during transfer (PSOW-OR, 8.69; 95% CI, 3.16-23.87; P < .001) compared with those without. The rate of any intracerebral hemorrhage and symptomatic intracerebral hemorrhage were similar between groups.Conclusions and RelevanceIn this multicenter cohort study, IVT initiated beyond 4.5 hours prior to interhospital transfer for EVT was associated with higher rates of recanalization during transfer and improved 3-month functional outcomes, without safety concerns. These findings offer encouraging support for clinical trials evaluating IVT in the late time window before interhospital transfer.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"51 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145644987","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}
Pub Date : 2025-11-24DOI: 10.1001/jamaneurol.2025.4650
Martin Ndengera, Paul E Constanthin, Felix T Kurz
{"title":"Interhemispheric Bullet Migration-A Surgical Dilemma.","authors":"Martin Ndengera, Paul E Constanthin, Felix T Kurz","doi":"10.1001/jamaneurol.2025.4650","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4650","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145587379","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}
Pub Date : 2025-11-24DOI: 10.1001/jamaneurol.2025.4691
Lee E Neilson,Isabella Montaño,Jasmine L May,Savanah Sicard,Yeilim Cho,Jeffrey J Iliff,Jonathan E Elliott,Miranda M Lim,Gregory D Scott
ImportanceObstructive sleep apnea (OSA) is associated with many health conditions, including dementia and early mortality. Prior epidemiological studies linking OSA with Parkinson disease (PD) are conflicting, and no studies have examined the influence of continuous positive airway pressure (CPAP), the criterion standard treatment for OSA, on PD risk.ObjectiveTo examine the association between OSA with incident Parkinson disease among US veterans and risk modification by CPAP.Design, Setting, and ParticipantsThis electronic health record (EHR)-based cohort study was conducted among US veterans from January 1, 1999, to December 30, 2022, with mean (SD) follow-up of 4.9 (1.8) years. Veterans with PD at the time of exposure or incomplete records were excluded. Data analysis was completed from September 2024 to September 2025.ExposureOSA was defined by its appropriate administrative code; CPAP usage was extracted from a semistructured medical interview field in the EHR.Main Outcomes and MeasuresThe primary outcome, cumulative incidence of PD, was calculated adjusting for competing risk of death after balancing for age, race, sex, and smoking status.ResultsA total of 13 737 081 US veterans were screened, and 11 310 411 veterans (1 109 543 female veterans [9.8%]) with mean (SD) age of 60.5 (14.7) years were included in analyses. Of included veterans, 1 552 505 (13.7%) had OSA. Veterans with OSA demonstrated 1.61 additional cases of PD (point estimate; 95% CI, 1.13-2.09) at 6 years from diagnosis per 1000 people compared to those without OSA. Results were confirmed when adjusting for body mass index, vascular comorbidities, psychiatric conditions, and relevant medications and were of greater magnitude in female veterans. Case numbers were significantly reduced when treated with CPAP early in the disease course.Conclusions and RelevanceIn this EHR-based cohort study, OSA appeared to be an independent risk factor for the later development of PD and could be modified by early treatment with CPAP. Effective screening measures and protocols for consistent adherence to CPAP may have large impacts on brain health.
{"title":"Obstructive Sleep Apnea, Positive Airway Pressure, and Implications of Early Treatment in Parkinson Disease.","authors":"Lee E Neilson,Isabella Montaño,Jasmine L May,Savanah Sicard,Yeilim Cho,Jeffrey J Iliff,Jonathan E Elliott,Miranda M Lim,Gregory D Scott","doi":"10.1001/jamaneurol.2025.4691","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4691","url":null,"abstract":"ImportanceObstructive sleep apnea (OSA) is associated with many health conditions, including dementia and early mortality. Prior epidemiological studies linking OSA with Parkinson disease (PD) are conflicting, and no studies have examined the influence of continuous positive airway pressure (CPAP), the criterion standard treatment for OSA, on PD risk.ObjectiveTo examine the association between OSA with incident Parkinson disease among US veterans and risk modification by CPAP.Design, Setting, and ParticipantsThis electronic health record (EHR)-based cohort study was conducted among US veterans from January 1, 1999, to December 30, 2022, with mean (SD) follow-up of 4.9 (1.8) years. Veterans with PD at the time of exposure or incomplete records were excluded. Data analysis was completed from September 2024 to September 2025.ExposureOSA was defined by its appropriate administrative code; CPAP usage was extracted from a semistructured medical interview field in the EHR.Main Outcomes and MeasuresThe primary outcome, cumulative incidence of PD, was calculated adjusting for competing risk of death after balancing for age, race, sex, and smoking status.ResultsA total of 13 737 081 US veterans were screened, and 11 310 411 veterans (1 109 543 female veterans [9.8%]) with mean (SD) age of 60.5 (14.7) years were included in analyses. Of included veterans, 1 552 505 (13.7%) had OSA. Veterans with OSA demonstrated 1.61 additional cases of PD (point estimate; 95% CI, 1.13-2.09) at 6 years from diagnosis per 1000 people compared to those without OSA. Results were confirmed when adjusting for body mass index, vascular comorbidities, psychiatric conditions, and relevant medications and were of greater magnitude in female veterans. Case numbers were significantly reduced when treated with CPAP early in the disease course.Conclusions and RelevanceIn this EHR-based cohort study, OSA appeared to be an independent risk factor for the later development of PD and could be modified by early treatment with CPAP. Effective screening measures and protocols for consistent adherence to CPAP may have large impacts on brain health.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"100 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145583450","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}
Pub Date : 2025-11-24DOI: 10.1001/jamaneurol.2025.4647
Katherine A Yao
{"title":"When I Applied to Medical School, My Grandfather Was Dying.","authors":"Katherine A Yao","doi":"10.1001/jamaneurol.2025.4647","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4647","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"83 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145583451","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}
Pub Date : 2025-11-24DOI: 10.1001/jamaneurol.2025.4470
John P Ney,Jaimie D Steinmetz,Ellen Anderson-Benge,Catherine W Gillespie,Amanda Becker,Xaviera Steele,Gregory J Esper
ImportanceNervous system health is a major contributor to population health, which is directly affected by neurological conditions and other disorders where nervous system damage occurs.ObjectiveTo quantify aggregated health loss from diseases affecting the nervous system, including neurological disorders; neurodevelopmental disorders; congenital, neonatal, and systemic illnesses; and infectious diseases in the United States.Design, Setting, and ParticipantsThis is a cross-sectional study of the Global Burden of Disease 2021 study data for nervous system health loss confined to the United States from 1990 through 2021 among the entire US population. Data analysis was performed from December 2021 to January 2025.ExposureThirty-six unique conditions that cause harm to the nervous system.Main Outcomes and MeasuresTotals and age-standardized estimates with 95% uncertainty intervals (UIs) for disability-adjusted life-years (DALYs), years lived with disability (YLDs), years of life lost (YLLs), total attributable deaths (where applicable), and prevalence.ResultsIn 2021, of the US population of 332.7 million, disorders affecting nervous system health impacted 180.3 million (95% UI, 170.7 million to 190.4 million) US individuals and were the top cause of disability, with 16.6 million (95% UI, 12.9 million to 20.9 million) DALYs. The most prevalent conditions were tension-type headache (121.9 million; 95% UI, 109.4 million to 135.1 million), migraine (57.7 million; 95% UI, 50.1 million to 66.1 million), and diabetic neuropathy (17.1 million; 95% UI, 14.4 million to 19.9 million). Conditions with the greatest collective disability were stroke (3.9 million DALYs; 95% UI, 3.5 million to 4.2 million DALYs), Alzheimer disease and other dementias (3.3 million DALYs; 95% UI, 1.6 million to 6.9 million DALYs), diabetic neuropathy (2.2 million DALYs; 95% UI, 1.5 million to 3.0 million DALYs), and migraine (2.1 million DALYs; 95% UI, 0.4 million to 4.6 million DALYs). Compared with age-standardized metrics in 1990, the prevalence of disorders affecting the nervous system was nearly identical (-0.2%; 95% UI, -1.5% to 1.9%), with decreased attributable deaths (-14.6%; 95% UI, -18.3% to -11.3%) but increased YLDs (9.8%; 95% UI, 4.6% to 16.6%). By state, Mississippi, Alabama, and Louisiana had the largest age-standardized DALY rates, while New York, Massachusetts, and New Jersey had the smallest.Conclusions and RelevanceDisorders affecting the nervous system are highly prevalent and cause disability for millions of US individuals, with reduced mortality leading to more YLDS. The United States should prioritize efforts to combat these conditions with development and implementation of new and effective prevention strategies, therapeutics, and focused rehabilitation.
{"title":"US Burden of Disorders Affecting the Nervous System: From the Global Burden of Disease 2021 Study.","authors":"John P Ney,Jaimie D Steinmetz,Ellen Anderson-Benge,Catherine W Gillespie,Amanda Becker,Xaviera Steele,Gregory J Esper","doi":"10.1001/jamaneurol.2025.4470","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4470","url":null,"abstract":"ImportanceNervous system health is a major contributor to population health, which is directly affected by neurological conditions and other disorders where nervous system damage occurs.ObjectiveTo quantify aggregated health loss from diseases affecting the nervous system, including neurological disorders; neurodevelopmental disorders; congenital, neonatal, and systemic illnesses; and infectious diseases in the United States.Design, Setting, and ParticipantsThis is a cross-sectional study of the Global Burden of Disease 2021 study data for nervous system health loss confined to the United States from 1990 through 2021 among the entire US population. Data analysis was performed from December 2021 to January 2025.ExposureThirty-six unique conditions that cause harm to the nervous system.Main Outcomes and MeasuresTotals and age-standardized estimates with 95% uncertainty intervals (UIs) for disability-adjusted life-years (DALYs), years lived with disability (YLDs), years of life lost (YLLs), total attributable deaths (where applicable), and prevalence.ResultsIn 2021, of the US population of 332.7 million, disorders affecting nervous system health impacted 180.3 million (95% UI, 170.7 million to 190.4 million) US individuals and were the top cause of disability, with 16.6 million (95% UI, 12.9 million to 20.9 million) DALYs. The most prevalent conditions were tension-type headache (121.9 million; 95% UI, 109.4 million to 135.1 million), migraine (57.7 million; 95% UI, 50.1 million to 66.1 million), and diabetic neuropathy (17.1 million; 95% UI, 14.4 million to 19.9 million). Conditions with the greatest collective disability were stroke (3.9 million DALYs; 95% UI, 3.5 million to 4.2 million DALYs), Alzheimer disease and other dementias (3.3 million DALYs; 95% UI, 1.6 million to 6.9 million DALYs), diabetic neuropathy (2.2 million DALYs; 95% UI, 1.5 million to 3.0 million DALYs), and migraine (2.1 million DALYs; 95% UI, 0.4 million to 4.6 million DALYs). Compared with age-standardized metrics in 1990, the prevalence of disorders affecting the nervous system was nearly identical (-0.2%; 95% UI, -1.5% to 1.9%), with decreased attributable deaths (-14.6%; 95% UI, -18.3% to -11.3%) but increased YLDs (9.8%; 95% UI, 4.6% to 16.6%). By state, Mississippi, Alabama, and Louisiana had the largest age-standardized DALY rates, while New York, Massachusetts, and New Jersey had the smallest.Conclusions and RelevanceDisorders affecting the nervous system are highly prevalent and cause disability for millions of US individuals, with reduced mortality leading to more YLDS. The United States should prioritize efforts to combat these conditions with development and implementation of new and effective prevention strategies, therapeutics, and focused rehabilitation.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"45 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145583452","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}
Pub Date : 2025-11-24DOI: 10.1001/jamaneurol.2025.4608
Liang En Wee,Wei Zhi Tan,Jo Yi Chow,Jue Tao Lim,Calvin Chiew,Po Ying Chia,Borame Dickens,Lee Ching Ng,Benjamin Ong,Yee Sin Leo,David Chien Lye,Kelvin Bryan Tan
ImportanceWith increasing global incidence of acute dengue virus (DENV) infection, more accurate estimates of the burden of neurological events following infection are required; however, population-based estimates are lacking.ObjectiveTo evaluate the risk and excess burden of neurological events in a cohort of DENV-infected adults in the acute postinfectious period vs population-based comparators without DENV infection.Design, Setting, and ParticipantsThis was a retrospective, population-based cohort study in Singapore. National registries were used to construct a cohort of all adults (aged ≥18 years) infected with DENV from January 1, 2017, through December 31, 2023, for whom the index date (time 0 [T0]) was taken as the date of notification, and a cohort of uninfected population-based comparators, for whom T0 was randomly assigned to match T0 distribution in DENV-infected cases. As the period overlapped with the COVID-19 pandemic, individuals infected with SARS-CoV-2 within 30 days of T0 were additionally excluded, as were individuals who died before T0 and uninfected comparators with no prior health care contact. Data analysis was performed from January 1, 2017, through March 30, 2024.ExposureDENV infection recorded in the national registry.Main Outcomes and MeasuresNew-incident neurological events, including any neurological event, memory loss, movement disorders, and other neurological disorders (eg, fatigue or malaise, encephalitis or encephalopathy), following DENV infection were identified using national health care claims records, and risk was assessed over the acute follow-up period. Odds of new-incident neurological events in DENV-infected cases vs uninfected comparators were estimated using overlap-weighted logistic regression at 30 to 90 days after T0.ResultsA total of 65 207 confirmed DENV-infected cases (mean [SD] age, 48.4 [17.8] years; 34 876 [53.5%] male) were compared against 1 616 865 uninfected comparators (mean [SD] age, 54.8 [18.3] years; 730 702 [45.2%] male). At 30 days following DENV infection, individuals with DENV infection, compared with uninfected individuals, had elevated odds of any new-incident neurological event (adjusted odds ratio [aOR], 9.69; 95% CI, 6.59-14.90), memory loss (aOR, 3.19; 95% CI, 1.36-8.69), movement disorders (aOR, 7.10; 95% CI, 2.49-29.18), and other neurological events (aOR, 14.32; 95% CI, 8.61-26.04); risk trajectories diverged up to 90 days after infection. However, the overall excess burden was modest, with less than 1 excess event per 100 cases. The DENV-infected cases, compared with uninfected individuals, had increased odds of memory loss (aOR, 2.99; 95% CI, 1.30-7.87) and movement disorders (aOR, 6.38; 95% CI, 2.23-25.96) only among those aged 60 years or older and in cases infected during DENV serotype 3 transmission.Conclusions and RelevanceDENV infection was associated with significantly higher odds of acute new-incident neurological events following infection, although the excess b
{"title":"Neurological Events Associated With Acute Dengue Infection.","authors":"Liang En Wee,Wei Zhi Tan,Jo Yi Chow,Jue Tao Lim,Calvin Chiew,Po Ying Chia,Borame Dickens,Lee Ching Ng,Benjamin Ong,Yee Sin Leo,David Chien Lye,Kelvin Bryan Tan","doi":"10.1001/jamaneurol.2025.4608","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4608","url":null,"abstract":"ImportanceWith increasing global incidence of acute dengue virus (DENV) infection, more accurate estimates of the burden of neurological events following infection are required; however, population-based estimates are lacking.ObjectiveTo evaluate the risk and excess burden of neurological events in a cohort of DENV-infected adults in the acute postinfectious period vs population-based comparators without DENV infection.Design, Setting, and ParticipantsThis was a retrospective, population-based cohort study in Singapore. National registries were used to construct a cohort of all adults (aged ≥18 years) infected with DENV from January 1, 2017, through December 31, 2023, for whom the index date (time 0 [T0]) was taken as the date of notification, and a cohort of uninfected population-based comparators, for whom T0 was randomly assigned to match T0 distribution in DENV-infected cases. As the period overlapped with the COVID-19 pandemic, individuals infected with SARS-CoV-2 within 30 days of T0 were additionally excluded, as were individuals who died before T0 and uninfected comparators with no prior health care contact. Data analysis was performed from January 1, 2017, through March 30, 2024.ExposureDENV infection recorded in the national registry.Main Outcomes and MeasuresNew-incident neurological events, including any neurological event, memory loss, movement disorders, and other neurological disorders (eg, fatigue or malaise, encephalitis or encephalopathy), following DENV infection were identified using national health care claims records, and risk was assessed over the acute follow-up period. Odds of new-incident neurological events in DENV-infected cases vs uninfected comparators were estimated using overlap-weighted logistic regression at 30 to 90 days after T0.ResultsA total of 65 207 confirmed DENV-infected cases (mean [SD] age, 48.4 [17.8] years; 34 876 [53.5%] male) were compared against 1 616 865 uninfected comparators (mean [SD] age, 54.8 [18.3] years; 730 702 [45.2%] male). At 30 days following DENV infection, individuals with DENV infection, compared with uninfected individuals, had elevated odds of any new-incident neurological event (adjusted odds ratio [aOR], 9.69; 95% CI, 6.59-14.90), memory loss (aOR, 3.19; 95% CI, 1.36-8.69), movement disorders (aOR, 7.10; 95% CI, 2.49-29.18), and other neurological events (aOR, 14.32; 95% CI, 8.61-26.04); risk trajectories diverged up to 90 days after infection. However, the overall excess burden was modest, with less than 1 excess event per 100 cases. The DENV-infected cases, compared with uninfected individuals, had increased odds of memory loss (aOR, 2.99; 95% CI, 1.30-7.87) and movement disorders (aOR, 6.38; 95% CI, 2.23-25.96) only among those aged 60 years or older and in cases infected during DENV serotype 3 transmission.Conclusions and RelevanceDENV infection was associated with significantly higher odds of acute new-incident neurological events following infection, although the excess b","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"29 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145583454","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}
Pub Date : 2025-11-17DOI: 10.1001/jamaneurol.2025.4478
Aristeidis H. Katsanos, Richard P. Whitlock, Emilie P. Belley-Côté, Katheryn Brady, Angela Wang, Abhilekh Srivastava, Gregory Jacquin, Viktor Weiss, Ondřej Volný, Martin Sramek, Andre Peeters, João Pedro Marto, Pawel Wrona, Anthoula Tsolaki, Linxin Li, Antonia Nucera, Robert Mikulik, Kanjana Perera, Luciana Catanese, Ashkan Shoamanesh, Mukul Sharma
Importance In the Left Atrial Appendage Occlusion Study III (LAAOS III), surgical occlusion of the LAA during cardiac surgery for patients with known history of atrial fibrillation (AF) substantially reduced the risk of stroke. Objective To assess the impact of LAAO on ischemic stroke subtype and outcome. Design, Setting, and Participants This was a post hoc exploratory analysis of the LAAOS III randomized clinical trial. Data were adjudicated from June 28, 2023, to November 29, 2023, and the main analyses took place from December 18, 2023, to April 29, 2024. The LAAOS III trial recruited participants from 105 centers in 27 countries between July 2012 and October 2018. Patients with AF and a CHA 2 DS 2 -VASc score of at least 2 undergoing cardiac surgery for other indications were included in the analysis. Interventions Surgical LAAO plus standard care vs standard care alone. Main Outcomes and Measures For strokes occurring during the trial, the functional outcome as measured by the modified Rankin Scale (mRS) score at day 7 or discharge, mortality, the presence of cortical infarcts, and the occurrence of infarcts of presumed cardioembolic origin were examined. Results Of 4811 participants in the LAAOS III trial followed up for 3.8 years, 273 had a first ischemic stroke. The mean (SD) age of participants at the time of the first ischemic stroke was 75 (7) years, 104 were female (38%), and 169 were male (62%). Participants allocated to receive LAAO had reduced (common odds ratio [OR], 0.80; 95% CI, 0.65-0.99) mRS scores at 7 days or discharge and a lower risk for mortality at 30 days (16.5% vs 20.1%; hazard ratio [HR], 0.55; 95% CI, 0.31-0.97) after a stroke event. Participants allocated to LAAO had fewer cortical infarcts on neuroimaging (46.2% vs 61.3%; difference in proportions: −15.2%; 95% CI, −26.7% to −3.7%), as well as a lower proportion of ischemic strokes of presumed cardioembolic etiology when compared with ischemic strokes in the no-LAAO group (42.9% vs 57.9%; difference in proportions: −15.1%; 95% CI, −26.5% to −3.7%). Conclusions and Relevance This study found that LAAO in patients with AF undergoing cardiac surgery was associated with a decreased risk of presumed cardioembolic stroke, reduced disability, and mortality from stroke. These findings underscore the benefit of LAAO for patients with AF undergoing cardiac surgery. Trial Registration ClinicalTrials.gov Identifier: NCT01561651
{"title":"Stroke Mechanism and Severity After Left Atrial Appendage Occlusion","authors":"Aristeidis H. Katsanos, Richard P. Whitlock, Emilie P. Belley-Côté, Katheryn Brady, Angela Wang, Abhilekh Srivastava, Gregory Jacquin, Viktor Weiss, Ondřej Volný, Martin Sramek, Andre Peeters, João Pedro Marto, Pawel Wrona, Anthoula Tsolaki, Linxin Li, Antonia Nucera, Robert Mikulik, Kanjana Perera, Luciana Catanese, Ashkan Shoamanesh, Mukul Sharma","doi":"10.1001/jamaneurol.2025.4478","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4478","url":null,"abstract":"Importance In the Left Atrial Appendage Occlusion Study III (LAAOS III), surgical occlusion of the LAA during cardiac surgery for patients with known history of atrial fibrillation (AF) substantially reduced the risk of stroke. Objective To assess the impact of LAAO on ischemic stroke subtype and outcome. Design, Setting, and Participants This was a post hoc exploratory analysis of the LAAOS III randomized clinical trial. Data were adjudicated from June 28, 2023, to November 29, 2023, and the main analyses took place from December 18, 2023, to April 29, 2024. The LAAOS III trial recruited participants from 105 centers in 27 countries between July 2012 and October 2018. Patients with AF and a CHA <jats:sub>2</jats:sub> DS <jats:sub>2</jats:sub> -VASc score of at least 2 undergoing cardiac surgery for other indications were included in the analysis. Interventions Surgical LAAO plus standard care vs standard care alone. Main Outcomes and Measures For strokes occurring during the trial, the functional outcome as measured by the modified Rankin Scale (mRS) score at day 7 or discharge, mortality, the presence of cortical infarcts, and the occurrence of infarcts of presumed cardioembolic origin were examined. Results Of 4811 participants in the LAAOS III trial followed up for 3.8 years, 273 had a first ischemic stroke. The mean (SD) age of participants at the time of the first ischemic stroke was 75 (7) years, 104 were female (38%), and 169 were male (62%). Participants allocated to receive LAAO had reduced (common odds ratio [OR], 0.80; 95% CI, 0.65-0.99) mRS scores at 7 days or discharge and a lower risk for mortality at 30 days (16.5% vs 20.1%; hazard ratio [HR], 0.55; 95% CI, 0.31-0.97) after a stroke event. Participants allocated to LAAO had fewer cortical infarcts on neuroimaging (46.2% vs 61.3%; difference in proportions: −15.2%; 95% CI, −26.7% to −3.7%), as well as a lower proportion of ischemic strokes of presumed cardioembolic etiology when compared with ischemic strokes in the no-LAAO group (42.9% vs 57.9%; difference in proportions: −15.1%; 95% CI, −26.5% to −3.7%). Conclusions and Relevance This study found that LAAO in patients with AF undergoing cardiac surgery was associated with a decreased risk of presumed cardioembolic stroke, reduced disability, and mortality from stroke. These findings underscore the benefit of LAAO for patients with AF undergoing cardiac surgery. Trial Registration ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://www.clinicaltrials.gov/study/NCT01561651\">NCT01561651</jats:ext-link>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"168 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531619","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}
Pub Date : 2025-11-17DOI: 10.1001/jamaneurol.2025.4658
{"title":"Error in Key Points and Methods.","authors":"","doi":"10.1001/jamaneurol.2025.4658","DOIUrl":"10.1001/jamaneurol.2025.4658","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12624450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-17DOI: 10.1001/jamaneurol.2025.4442
Ann Berger
From clinician to patient, the author’s journey with neuromuscular disease illuminates the evolving dialogue between medical possibility, personal values, and the meaning of care.
{"title":"Breath and Balance","authors":"Ann Berger","doi":"10.1001/jamaneurol.2025.4442","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4442","url":null,"abstract":"From clinician to patient, the author’s journey with neuromuscular disease illuminates the evolving dialogue between medical possibility, personal values, and the meaning of care.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"120 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531618","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}
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