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Plasma Phosphorylated Tau 217 and Amyloid Burden in Older Adults Without Cognitive Impairment: A Meta-Analysis. 无认知障碍的老年人血浆磷酸化Tau 217和淀粉样蛋白负担:一项荟萃分析。
IF 29 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-12-01 DOI: 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.
基于血液的生物标志物(BBMs)在有症状个体检测阿尔茨海默病(AD)病理变化方面具有很高的准确性。在常染色体显性阿尔茨海默病和唐氏综合症患者中,这两个人群几乎都有阿尔茨海默病的病理发展,在临床发病前几年就可以检测到脑卒中的升高,这支持了它们在这些病例中识别临床前疾病的效用。在脑卒中中,血浆磷酸化的tau217 (p-tau217)与AD病理的体内标志物具有很强的一致性。然而,其识别无认知障碍的老年人淀粉样蛋白阳性的能力在不同的研究和环境中仍然存在差异。目的评估已发表的比较淀粉样蛋白阳性和淀粉样蛋白阴性老年人无认知障碍的研究中p-tau217平均差异的标准化效应大小和分类准确性。数据来源pubmed, Embase和EBSCOhost数据库从成立到2025年9月1日。研究选择:对无认知障碍、淀粉样蛋白阳性或淀粉样蛋白阴性的个体进行观察性研究或随机临床试验,并报告p-tau217水平的数值数据。数据提取和综合本研究采用了系统评价和荟萃分析首选报告项目(PRISMA)报告指南。两位作者独立进行了文献检索,以确定没有认知障碍的老年人的研究,这些老年人被分类为淀粉样蛋白阳性或淀粉样蛋白阴性,其中p-tau217被量化。主要结局和测量方法采用标准化平均差(Hedges g)来表征p-tau - 217平均水平的差异。用曲线下面积(AUC)值来总结p-tau217在识别淀粉样蛋白阳性个体中的诊断准确性。采用亚组分析和敏感性分析研究间异质性。采用Egger检验评估发表偏倚。结果分析了来自18篇出版物的7834名参与者(淀粉样蛋白阳性2533名,淀粉样蛋白阴性5301名)的数据。p-tau217的效应量很大(Hedges g = 1.50; 95% CI, 1.33-1.68)。p-tau217的值在识别无认知障碍的淀粉样蛋白阳性个体方面也显示出很高的准确性(AUC = 0.87; 95% CI, 0.85-0.90)。结论与相关性这些发现表明血浆p-tau217可以可靠地检测阿尔茨海默病临床前阶段的病理。这些发现支持血浆p-tau217作为早期识别AD的可扩展、微创工具的临床应用,特别是在及时干预疾病修饰疗法可能在减缓或预防疾病进展方面提供最大益处的情况下。
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引用次数: 0
Intravenous Thrombolysis Use in the Late Time Window Before Interhospital Transfer for Thrombectomy. 静脉溶栓在院间转栓前晚时间窗的应用
IF 29 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-12-01 DOI: 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。
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引用次数: 0
Interhemispheric Bullet Migration-A Surgical Dilemma. 半球间子弹迁移-一个外科难题。
IF 21.3 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-11-24 DOI: 10.1001/jamaneurol.2025.4650
Martin Ndengera, Paul E Constanthin, Felix T Kurz
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引用次数: 0
Obstructive Sleep Apnea, Positive Airway Pressure, and Implications of Early Treatment in Parkinson Disease. 阻塞性睡眠呼吸暂停、气道正压通气和帕金森病早期治疗的意义。
IF 29 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-11-24 DOI: 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.
阻塞性睡眠呼吸暂停(OSA)与许多健康状况有关,包括痴呆和早期死亡。先前的流行病学研究将OSA与帕金森病(PD)联系起来是相互矛盾的,并且没有研究检查持续气道正压通气(CPAP) (OSA的标准治疗方法)对PD风险的影响。目的探讨美国退伍军人阻塞性睡眠呼吸暂停与帕金森病发病的关系及CPAP的风险调节作用。设计、环境和参与者这项基于电子健康记录(EHR)的队列研究于1999年1月1日至2022年12月30日在美国退伍军人中进行,平均(SD)随访4.9(1.8)年。在暴露时患有PD或记录不完整的退伍军人被排除在外。数据分析时间为2024年9月至2025年9月。暴露性呼吸暂停症由其适当的行政法规定义;CPAP的使用情况是从EHR的半结构化医疗访谈字段中提取的。主要结局和测量主要结局是PD的累积发病率,在平衡了年龄、种族、性别和吸烟状况后,计算了竞争死亡风险。结果共筛选13 737 081名美国退伍军人,纳入11 310 411名退伍军人(1 109 543名,占9.8%),平均(SD)年龄为60.5(14.7)岁。在纳入的退伍军人中,1 552 505(13.7%)患有OSA。与没有OSA的退伍军人相比,患有OSA的退伍军人在诊断后6年内每1000人中有1.61例额外的PD病例(点估计;95% CI, 1.13-2.09)。在调整了身体质量指数、血管合并症、精神状况和相关药物后,结果得到了证实,并且在女性退伍军人中更为显著。在病程早期使用CPAP治疗,病例数显著减少。结论和相关性在这项基于ehr的队列研究中,OSA似乎是PD后期发展的独立危险因素,可以通过早期使用CPAP治疗来改善。持续坚持CPAP的有效筛查措施和方案可能对脑健康产生重大影响。
{"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}
引用次数: 0
When I Applied to Medical School, My Grandfather Was Dying. 当我申请医学院的时候,我的祖父快要死了。
IF 29 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-11-24 DOI: 10.1001/jamaneurol.2025.4647
Katherine A Yao
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引用次数: 0
US Burden of Disorders Affecting the Nervous System: From the Global Burden of Disease 2021 Study. 影响神经系统的疾病负担:来自2021年全球疾病负担研究。
IF 29 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-11-24 DOI: 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.
神经系统健康是人类健康的一个主要因素,它直接受到神经系统疾病和其他神经系统损伤疾病的影响。目的量化神经系统疾病(包括神经系统疾病)造成的总体健康损失;神经发育障碍;先天性、新生儿和全身疾病;和传染病设计、环境和参与者:这是一项关于全球疾病负担2021研究数据的横断面研究,该研究数据仅限于1990年至2021年美国所有美国人口的神经系统健康损失。数据分析时间为2021年12月至2025年1月。暴露36种对神经系统造成伤害的独特情况。主要结局和测量方法残疾调整生命年(DALYs)、残疾生活年(YLDs)、丧失生命年(YLLs)、总归因死亡(如适用)和患病率的统计和年龄标准化估计(95%不确定区间)。结果2021年,在美国3.327亿人口中,影响神经系统健康的疾病影响了1.803亿(95% UI, 1.707亿至1.904亿)美国人,是导致残疾的首要原因,有1660万(95% UI, 1290万至2090万)DALYs。最常见的疾病是紧张性头痛(1.190亿;95%尿失禁,1.094亿至1.351亿)、偏头痛(5770万;95%尿失禁,5010万至6610万)和糖尿病性神经病变(1710万;95%尿失禁,1440万至1990万)。集体残疾最大的疾病是中风(390万DALYs; 95% UI, 350万至420万DALYs)、阿尔茨海默病和其他痴呆症(330万DALYs; 95% UI, 160万至690万DALYs)、糖尿病神经病变(220万DALYs; 95% UI, 150万至300万DALYs)和偏头痛(210万DALYs; 95% UI, 40万至460万DALYs)。与1990年的年龄标准化指标相比,影响神经系统疾病的患病率几乎相同(-0.2%;95% UI, -1.5%至1.9%),可归因死亡率下降(-14.6%;95% UI, -18.3%至-11.3%),但YLDs增加(9.8%;95% UI, 4.6%至16.6%)。按州划分,密西西比州、阿拉巴马州和路易斯安那州的年龄标准化DALY率最高,而纽约州、马萨诸塞州和新泽西州的年龄标准化DALY率最低。影响神经系统的疾病非常普遍,并导致数百万美国人残疾,死亡率降低导致更多的YLDS。美国应该通过开发和实施新的有效的预防策略、治疗方法和重点康复来优先解决这些问题。
{"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}
引用次数: 0
Neurological Events Associated With Acute Dengue Infection. 与急性登革热感染相关的神经系统事件。
IF 29 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-11-24 DOI: 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
随着全球急性登革热病毒(DENV)感染发病率的增加,需要更准确地估计感染后神经系统事件的负担;然而,缺乏以人口为基础的估计。目的评估DENV感染的成年人在急性感染后期与未感染DENV的人群为基础的比较者的神经事件风险和额外负担。设计、环境和参与者这是一项在新加坡进行的回顾性、基于人群的队列研究。使用国家注册中心构建了一个队列,包括2017年1月1日至2023年12月31日期间感染DENV的所有成年人(年龄≥18岁),其中以索引日期(时间0 [T0])作为通报日期,以及一个基于未感染人群的比较者队列,其中T0随机分配,以匹配DENV感染病例的T0分布。由于该时期与COVID-19大流行重叠,因此在T0后30天内感染SARS-CoV-2的个体,以及在T0之前死亡的个体和先前没有卫生保健接触的未感染比较者也被排除在外。数据分析时间为2017年1月1日至2024年3月30日。国家登记处记录的denv感染。主要结局和测量方法使用国家卫生保健索赔记录确定DENV感染后新发生的神经系统事件,包括任何神经系统事件、记忆丧失、运动障碍和其他神经系统疾病(如疲劳或不适、脑炎或脑病),并在急性随访期间评估风险。在T0后30至90天,使用重叠加权逻辑回归估计denv感染病例与未感染比较者新发生神经事件的几率。结果共有65 207例确诊denv感染病例(平均[SD]年龄48.4[17.8]岁,男性34 876例[53.5%])与1 616 865例(平均[SD]年龄54.8[18.3]岁,男性730 702例[45.2%])进行比较。在DENV感染后30天,DENV感染个体与未感染个体相比,任何新发生的神经事件(调整优势比[aOR], 9.69, 95% CI, 6.59-14.90)、记忆丧失(aOR, 3.19, 95% CI, 1.36-8.69)、运动障碍(aOR, 7.10, 95% CI, 2.49-29.18)和其他神经事件(aOR, 14.32, 95% CI, 8.61-26.04)的几率升高;风险轨迹在感染后90天内出现分化。然而,总体的额外负担是适度的,每100个病例中不到1个额外事件。与未感染的个体相比,DENV感染的病例仅在60岁或以上以及DENV血清3型传播期间感染的病例中出现记忆丧失(aOR, 2.99; 95% CI, 1.30-7.87)和运动障碍(aOR, 6.38; 95% CI, 2.23-25.96)的几率增加。结论和相关性env感染与感染后急性新发神经事件的发生率显著升高相关,尽管额外负担是适度的。老年人应监测DENV感染后更广泛的潜在神经系统并发症。
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引用次数: 0
Stroke Mechanism and Severity After Left Atrial Appendage Occlusion 左心耳闭塞后卒中机制及严重程度
IF 29 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-11-17 DOI: 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
在左心耳闭塞研究III (LAAOS III)中,已知心房颤动(AF)病史的患者在心脏手术期间手术闭塞左心耳可显著降低卒中的风险。目的探讨LAAO对缺血性脑卒中亚型及转归的影响。设计、环境和参与者:这是一项LAAOS III随机临床试验的事后探索性分析。数据评审时间为2023年6月28日至11月29日,主要分析时间为2023年12月18日至2024年4月29日。LAAOS III试验在2012年7月至2018年10月期间从27个国家的105个中心招募了参与者。房颤和CHA 2 ds2 -VASc评分至少为2分的患者因其他适应症接受心脏手术被纳入分析。干预措施:手术LAAO加标准治疗vs单独标准治疗。对于试验期间发生的卒中,在第7天或出院时,通过改良兰金量表(mRS)评分测量的功能结局、死亡率、皮质梗死的存在以及假定心栓子起源的梗死的发生进行了检查。结果在LAAOS III试验的4811名参与者中,随访3.8年,273例首次缺血性中风。受试者首次缺血性卒中时的平均(SD)年龄为75(7)岁,其中女性104人(38%),男性169人(62%)。被分配接受LAAO的参与者在卒中事件发生后7天或出院时mRS评分降低(常见优势比[OR], 0.80; 95% CI, 0.65-0.99), 30天死亡风险降低(16.5% vs 20.1%;风险比[HR], 0.55; 95% CI, 0.31-0.97)。分配到LAAO的参与者在神经影像学上有更少的皮质梗死(46.2% vs 61.3%;比例差异:- 15.2%;95% CI, - 26.7%至- 3.7%),并且与非LAAO组的缺血性卒中相比,假定的心栓塞病因缺血性卒中的比例更低(42.9% vs 57.9%;比例差异:- 15.1%;95% CI, - 26.5%至- 3.7%)。本研究发现,接受心脏手术的房颤患者的LAAO与心脏栓塞性卒中的风险降低、卒中致残率和死亡率降低相关。这些发现强调了LAAO对接受心脏手术的房颤患者的益处。临床试验注册:ClinicalTrials.gov标识符:NCT01561651
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引用次数: 0
Error in Key Points and Methods. 关键点和方法错误。
IF 21.3 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-11-17 DOI: 10.1001/jamaneurol.2025.4658
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引用次数: 0
Breath and Balance 呼吸与平衡
IF 29 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-11-17 DOI: 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.
从临床医生到患者,作者与神经肌肉疾病的旅程阐明了医疗可能性,个人价值观和护理意义之间不断发展的对话。
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引用次数: 0
期刊
JAMA neurology
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