Pub Date : 2026-02-09DOI: 10.1001/jamaneurol.2026.0046
{"title":"Error in the Funding/Support Statement.","authors":"","doi":"10.1001/jamaneurol.2026.0046","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.0046","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":21.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142384","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 : 2026-02-09DOI: 10.1001/jamaneurol.2025.5493
Amy A Gelfand, Serena L Orr, Daniel J Shapiro
{"title":"Glucocorticoids for Preventing Migraine Recurrence in the Emergency Department.","authors":"Amy A Gelfand, Serena L Orr, Daniel J Shapiro","doi":"10.1001/jamaneurol.2025.5493","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5493","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":21.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142474","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 : 2026-02-09DOI: 10.1001/jamaneurol.2025.5625
Emanuele Cerulli Irelli, Roberta Roberti, Maria Sole Borioni, Francesca Anzellotti, Vincenzo Belcastro, Simone Beretta, Giovanni Boero, Paolo Bonanni, Valentina Chiesa, Alfredo D'Aniello, Filippo Dainese, Francesco Deleo, Giovanni De Maria, Giancarlo Di Gennaro, Gianfranco Di Gennaro, Giuseppe Didato, Fedele Dono, Giovanni Falcicchio, Edoardo Ferlazzo, Francesco Fortunato, Angela La Neve, Oriano Mecarelli, Elisa Montalenti, Alessandra Morano, Annacarmen Nilo, Francesca Felicia Operto, Francesco Paladin, Angelo Pascarella, Giada Pauletto, Nicola Pietrafusa, Pietro Pignatta, Patrizia Pulitano, Rosaria Renna, Eleonora Rosati, Ilaria Sammarra, Carlo Di Bonaventura, Emilio Russo, Simona Lattanzi
<p><strong>Importance: </strong>Treatment decisions in drug-resistant focal epilepsy remain largely empirical, as direct comparative evidence among newer antiseizure medications (ASMs) is limited. Real-world data can complement randomized clinical trials by providing insights into long-term effectiveness and safety across diverse populations.</p><p><strong>Objective: </strong>To compare effectiveness and safety of brivaracetam, cenobamate, lacosamide, and perampanel as adjunctive therapies in adults with drug-resistant focal epilepsy.</p><p><strong>Design, setting, and participants: </strong>This was a multicenter pooled analysis of 4 previously conducted retrospective real-world medical record-review studies (January 2017-January 2024). Included were adult patients (aged ≥16 years) with drug-resistant focal epilepsy, as defined by the International League Against Epilepsy. Participants were recruited from 71 epilepsy centers.</p><p><strong>Exposures: </strong>Add-on treatment with brivaracetam, cenobamate, lacosamide, or perampanel.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was the responder rate at 6 months, defined as greater than or equal to 50% seizure frequency reduction from baseline. Secondary outcomes included 12-month responder rate, seizure freedom (≥3 months at 6 months and ≥6 months at 12 months), and 12-month ASM retention. Safety was assessed by incidence of adverse effects. Generalized linear mixed models adjusted for demographic and clinical covariates were used to compare treatment outcomes, with cenobamate as reference ASM.</p><p><strong>Results: </strong>Of 2386 ASM prescriptions screened, 1993 prescriptions from 1949 patients (1036 of 1947 female [53.2%]; sex information was missing in 0.1% of prescriptions) with a median (IQR) age of 42 (29-55) years at ASM prescription, met inclusion criteria and were included in the pooled analysis. Brivaracetam accounted for 953 prescriptions (47.8%), followed by perampanel (607 [30.5%]), lacosamide (241 [12.1%]), and cenobamate (192 [9.6%]). After adjustment, cenobamate demonstrated significantly higher odds of 50% or greater response at 6 months compared with brivaracetam (odds ratio [OR], 0.18; 95% CI, 0.12-0.28; P < .001), perampanel (OR, 0.26; 95% CI, 0.16-0.42; P < .001), and lacosamide (OR, 0.29; 95% CI, 0.17-0.49; P < .001). Results were consistent for secondary effectiveness outcomes at 12 months, with cenobamate outperforming other ASMs in terms of 50% or greater response and seizure freedom. Cenobamate was associated with the highest rate of adverse effects during follow-up (111 [57.8%]), and lacosamide was associated with the lowest (35 [14.8%]). Cenobamate was associated with a higher likelihood of treatment retention at 12 months compared with brivaracetam (OR, 0.43; 95% CI, 0.26-0.69; P < .001) and perampanel (OR, 0.56; 95% CI, 0.32-0.99; P = .047), with no significant difference vs lacosamide (OR, 0.81; 95% CI, 0.41-1.59; P = .53).</p><p><stron
{"title":"Comparative Effectiveness of Brivaracetam, Cenobamate, Lacosamide, and Perampanel in Focal Epilepsy.","authors":"Emanuele Cerulli Irelli, Roberta Roberti, Maria Sole Borioni, Francesca Anzellotti, Vincenzo Belcastro, Simone Beretta, Giovanni Boero, Paolo Bonanni, Valentina Chiesa, Alfredo D'Aniello, Filippo Dainese, Francesco Deleo, Giovanni De Maria, Giancarlo Di Gennaro, Gianfranco Di Gennaro, Giuseppe Didato, Fedele Dono, Giovanni Falcicchio, Edoardo Ferlazzo, Francesco Fortunato, Angela La Neve, Oriano Mecarelli, Elisa Montalenti, Alessandra Morano, Annacarmen Nilo, Francesca Felicia Operto, Francesco Paladin, Angelo Pascarella, Giada Pauletto, Nicola Pietrafusa, Pietro Pignatta, Patrizia Pulitano, Rosaria Renna, Eleonora Rosati, Ilaria Sammarra, Carlo Di Bonaventura, Emilio Russo, Simona Lattanzi","doi":"10.1001/jamaneurol.2025.5625","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5625","url":null,"abstract":"<p><strong>Importance: </strong>Treatment decisions in drug-resistant focal epilepsy remain largely empirical, as direct comparative evidence among newer antiseizure medications (ASMs) is limited. Real-world data can complement randomized clinical trials by providing insights into long-term effectiveness and safety across diverse populations.</p><p><strong>Objective: </strong>To compare effectiveness and safety of brivaracetam, cenobamate, lacosamide, and perampanel as adjunctive therapies in adults with drug-resistant focal epilepsy.</p><p><strong>Design, setting, and participants: </strong>This was a multicenter pooled analysis of 4 previously conducted retrospective real-world medical record-review studies (January 2017-January 2024). Included were adult patients (aged ≥16 years) with drug-resistant focal epilepsy, as defined by the International League Against Epilepsy. Participants were recruited from 71 epilepsy centers.</p><p><strong>Exposures: </strong>Add-on treatment with brivaracetam, cenobamate, lacosamide, or perampanel.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was the responder rate at 6 months, defined as greater than or equal to 50% seizure frequency reduction from baseline. Secondary outcomes included 12-month responder rate, seizure freedom (≥3 months at 6 months and ≥6 months at 12 months), and 12-month ASM retention. Safety was assessed by incidence of adverse effects. Generalized linear mixed models adjusted for demographic and clinical covariates were used to compare treatment outcomes, with cenobamate as reference ASM.</p><p><strong>Results: </strong>Of 2386 ASM prescriptions screened, 1993 prescriptions from 1949 patients (1036 of 1947 female [53.2%]; sex information was missing in 0.1% of prescriptions) with a median (IQR) age of 42 (29-55) years at ASM prescription, met inclusion criteria and were included in the pooled analysis. Brivaracetam accounted for 953 prescriptions (47.8%), followed by perampanel (607 [30.5%]), lacosamide (241 [12.1%]), and cenobamate (192 [9.6%]). After adjustment, cenobamate demonstrated significantly higher odds of 50% or greater response at 6 months compared with brivaracetam (odds ratio [OR], 0.18; 95% CI, 0.12-0.28; P < .001), perampanel (OR, 0.26; 95% CI, 0.16-0.42; P < .001), and lacosamide (OR, 0.29; 95% CI, 0.17-0.49; P < .001). Results were consistent for secondary effectiveness outcomes at 12 months, with cenobamate outperforming other ASMs in terms of 50% or greater response and seizure freedom. Cenobamate was associated with the highest rate of adverse effects during follow-up (111 [57.8%]), and lacosamide was associated with the lowest (35 [14.8%]). Cenobamate was associated with a higher likelihood of treatment retention at 12 months compared with brivaracetam (OR, 0.43; 95% CI, 0.26-0.69; P < .001) and perampanel (OR, 0.56; 95% CI, 0.32-0.99; P = .047), with no significant difference vs lacosamide (OR, 0.81; 95% CI, 0.41-1.59; P = .53).</p><p><stron","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":21.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142416","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 : 2026-02-02DOI: 10.1001/jamaneurol.2025.5581
Alec M. Czaplicki, Ira Frahmand Driscoll, Yue Ma, J. Max Gaitán, Barbara B. Bendlin, Sterling C. Johnson, Sanjay Asthana, Dena B. Dubal, Ozioma C. Okonkwo
Importance Ventricle-brain volume ratio (VBR), a marker of cerebral atrophy, is a robust correlate of cognition and a predictor of Alzheimer disease (AD) progression. Higher circulating concentrations of the longevity protein klotho have been linked to better cognition, but whether klotho modifies the known association between age-related brain atrophy and cognitive decline is unclear. Objective To examine whether serum klotho moderates the association between VBR and cognition and whether this association differs in younger adults (age ≤61.6 years; median split) compared with older adults. Design, Setting, and Participants This was a cross-sectional study using data from the Wisconsin Alzheimer Disease Research Center and the Wisconsin Registry for Alzheimer Prevention, collected from 2009 to 2023. This was a community-based, longitudinal study at a research center. Included in the analysis were middle-aged and older adults without cognitive impairment, most with a parental history of AD, who underwent neuropsychological testing, magnetic resonance image, and venipuncture. Exposure Serum soluble α-klotho concentration, measured via enzyme-linked immunosorbent assay. Main Outcomes and Measures Outcome measures included composite z scores for global cognition, executive function, delayed recall, and immediate learning. VBR was calculated as total ventricular volume divided by total brain volume ×100. Results Across the entire sample (308 participants; mean [SD] age, 61.3 [6.5] years; 246 female [80%]; parental history of AD, 227 [74%]), the VBR × klotho interaction was significant, whereby those with higher serum klotho levels performed better on tests assessing global cognition (mean [SE], 0.35 [0.14]; 95% CI, 0.08-0.62; P = .01) and executive function (mean [SE], 0.41 [0.15]; 95% CI, 0.11-0.71; P = .01) but not delayed recall or immediate learning, despite having more brain atrophy. VBR × klotho interactions were not significant in the younger group. In the older group, the VBR × klotho interaction was significant, whereby those with higher circulating klotho levels performed better on tests of global cognition (mean [SE], 0.59 [0.24]; 95% CI, 0.12-1.06; P = .01), executive function (mean [SE], 0.71 [0.27]; 95% CI, 0.19-1.24; P = .01), and immediate learning (mean [SE], 0.59 [0.27]; 95% CI, 0.06-1.20; P = .03) but not delayed recall, despite having more brain atrophy. Conclusions and Relevance Results suggest that circulating serum klotho levels modified the known adverse association between age-related brain atrophy and cognition in older, but not younger, adults at risk for AD, suggesting that the neuroprotective effects of klotho may be age dependent.
脑室-脑体积比（VBR）是脑萎缩的一个标志，是认知和阿尔茨海默病（AD）进展的一个强有力的预测因子。高循环浓度的长寿蛋白klotho与更好的认知能力有关，但klotho是否会改变与年龄相关的脑萎缩和认知能力下降之间的已知联系尚不清楚。目的探讨血清klotho是否调节VBR与认知之间的关联，以及这种关联在年轻人（年龄≤61.6岁；中位数分裂）中是否与老年人不同。设计、设置和参与者这是一项横断面研究，使用了威斯康星州阿尔茨海默病研究中心和威斯康星州阿尔茨海默病预防登记处从2009年到2023年收集的数据。这是一个在研究中心进行的以社区为基础的纵向研究。纳入分析的是没有认知障碍的中老年人，大多数父母有阿尔茨海默病病史，他们接受了神经心理测试、磁共振成像和静脉穿刺。酶联免疫吸附法测定血清可溶性α-克洛索浓度。主要结果和测量结果包括全球认知、执行功能、延迟回忆和即时学习的综合z分数。VBR计算方法为总心室容积除以总脑容积×100。结果在整个样本中（308名参与者，平均[SD]年龄61.3[6.5]岁，246名女性[80%]，父母AD病史227 [74%]），VBR与klotho的相互作用是显著的，血清klotho水平较高的人在评估整体认知（平均[SE]， 0.35 [0.14]; 95% CI, 0.08-0.62; P = 0.01）和执行功能（平均[SE]， 0.41 [0.15]; 95% CI, 0.11-0.71; P = 0.01）的测试中表现更好，但没有延迟回忆或即时学习，尽管有更多的脑萎缩。VBR与klotho相互作用在年轻组中不显著。在老年组中，VBR与klotho的相互作用是显著的，因此那些循环klotho水平较高的人在整体认知（平均[SE]， 0.59 [0.24]; 95% CI, 0.12-1.06; P = 0.01）、执行功能（平均[SE]， 0.71 [0.27]; 95% CI, 0.19-1.24; P = 0.01）和即时学习（平均[SE]， 0.59 [0.27]; 95% CI, 0.06-1.20; P = 0.03）的测试中表现更好，但没有延迟回忆，尽管有更多的脑萎缩。结论和相关性结果表明，在老年AD高危人群中，循环血清klotho水平改变了已知的与年龄相关的脑萎缩与认知之间的不良关联，而不是年轻人，这表明klotho的神经保护作用可能是年龄依赖性的。
{"title":"Serum Klotho Levels, Brain Structure, and Cognitive Performance","authors":"Alec M. Czaplicki, Ira Frahmand Driscoll, Yue Ma, J. Max Gaitán, Barbara B. Bendlin, Sterling C. Johnson, Sanjay Asthana, Dena B. Dubal, Ozioma C. Okonkwo","doi":"10.1001/jamaneurol.2025.5581","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5581","url":null,"abstract":"Importance Ventricle-brain volume ratio (VBR), a marker of cerebral atrophy, is a robust correlate of cognition and a predictor of Alzheimer disease (AD) progression. Higher circulating concentrations of the longevity protein klotho have been linked to better cognition, but whether klotho modifies the known association between age-related brain atrophy and cognitive decline is unclear. Objective To examine whether serum klotho moderates the association between VBR and cognition and whether this association differs in younger adults (age ≤61.6 years; median split) compared with older adults. Design, Setting, and Participants This was a cross-sectional study using data from the Wisconsin Alzheimer Disease Research Center and the Wisconsin Registry for Alzheimer Prevention, collected from 2009 to 2023. This was a community-based, longitudinal study at a research center. Included in the analysis were middle-aged and older adults without cognitive impairment, most with a parental history of AD, who underwent neuropsychological testing, magnetic resonance image, and venipuncture. Exposure Serum soluble α-klotho concentration, measured via enzyme-linked immunosorbent assay. Main Outcomes and Measures Outcome measures included composite <jats:italic toggle=\"yes\">z</jats:italic> scores for global cognition, executive function, delayed recall, and immediate learning. VBR was calculated as total ventricular volume divided by total brain volume ×100. Results Across the entire sample (308 participants; mean [SD] age, 61.3 [6.5] years; 246 female [80%]; parental history of AD, 227 [74%]), the VBR × klotho interaction was significant, whereby those with higher serum klotho levels performed better on tests assessing global cognition (mean [SE], 0.35 [0.14]; 95% CI, 0.08-0.62; <jats:italic toggle=\"yes\">P</jats:italic> = .01) and executive function (mean [SE], 0.41 [0.15]; 95% CI, 0.11-0.71; <jats:italic toggle=\"yes\">P</jats:italic> = .01) but not delayed recall or immediate learning, despite having more brain atrophy. VBR × klotho interactions were not significant in the younger group. In the older group, the VBR × klotho interaction was significant, whereby those with higher circulating klotho levels performed better on tests of global cognition (mean [SE], 0.59 [0.24]; 95% CI, 0.12-1.06; <jats:italic toggle=\"yes\">P</jats:italic> = .01), executive function (mean [SE], 0.71 [0.27]; 95% CI, 0.19-1.24; <jats:italic toggle=\"yes\">P</jats:italic> = .01), and immediate learning (mean [SE], 0.59 [0.27]; 95% CI, 0.06-1.20; <jats:italic toggle=\"yes\">P</jats:italic> = .03) but not delayed recall, despite having more brain atrophy. Conclusions and Relevance Results suggest that circulating serum klotho levels modified the known adverse association between age-related brain atrophy and cognition in older, but not younger, adults at risk for AD, suggesting that the neuroprotective effects of klotho may be age dependent.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"8 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101431","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 : 2026-02-02DOI: 10.1001/jamaneurol.2025.5530
Jihwan Yun, Jungah Lee, Daeun Shin, Eun Hye Lee, Jun Pyo Kim, Hongki Ham, Yuna Gu, Min Young Chun, Sung Hoon Kang, Hee Jin Kim, Duk L Na, Ko Woon Kim, Si Eun Kim, Yeshin Kim, Jaeho Kim, Na-Yeon Jung, Yeo Jin Kim, Soo Hyun Cho, Jin San Lee, Seonghyeon Kim, Henrik Zetterberg, Kaj Blennow, Fernando Gonzalez-Ortiz, Nicholas J Ashton, Joel B Braunstein, Philip B Verghese, Tim West, Matthew R Meyer, Sang Won Seo, Hyemin Jang
<p><strong>Importance: </strong>Plasma phosphorylated p-tau 217 levels vary with biological factors such as kidney dysfunction, body mass index (BMI), and anemia. It remains unclear whether a biological subgroup-specific optimal cutoff or a double-cutoff strategy could enhance diagnostic accuracy and cost efficiency beyond the standard single cutoff.</p><p><strong>Objective: </strong>To compare the diagnostic and economic performance of 3 plasma p-tau217 classification strategies for detecting amyloid-β (Aβ) positivity: standard single cutoff, subgroup-specific optimal cutoff, and double cutoff.</p><p><strong>Design, setting, and participants: </strong>This cohort study was a multicenter cross-sectional study conducted from 2016 to 2023; analyses were completed in 2025. Participants were recruited from multiple memory clinics and community-based cohorts. All participants had amyloid positron emission tomography (PET) imaging, clinical evaluation, and p-tau217 testing with measures of estimated glomerular filtration rate (eGFR), BMI, and hemoglobin. Measurements of p-tau217 were made using UGOT Simoa and Roche Elecsys, and the %p-tau217 ratio was assessed using a tau multianalyte assay (C2N Diagnostics LLC).</p><p><strong>Exposures: </strong>Kidney function (chronic kidney disease [CKD], eGFR <60 mL/min/1.73 m2; advanced CKD, eGFR <45 mL/min/1.73 m2), underweight (BMI <18.5), obesity (BMI ≥27.5), and anemia (hemoglobin <12 g/dL in women, <13 g/dL in men).</p><p><strong>Main outcomes and measures: </strong>Plasma p-tau217 concentration; standard single cutoff, optimal cutoffs, and double cutoff for Aβ positivity (Centiloid ≥25.5); accuracy; and cost-effectiveness estimated from false-positive, false-negative, and confirmatory imaging costs.</p><p><strong>Results: </strong>A total of 2571 participants were analyzed with UGOT, 1578 with Roche, and 304 with the C2N %p-tau217 ratio. The mean (SD) age was similar across cohorts (71.3 [8.6] years in the UGOT cohort, 71.3 [8.5] years in the Roche cohort, and 71.8 [7.8] years in the C2N cohort); there were 1633 (63.5%), 1006 (63.8%), and 191 (62.8%) women and 938 (36.5%), 572 (36.2%), and 113 (37.2%) men, respectively. In the UGOT cohort, the optimal cutoff improved diagnostic accuracy compared with the standard single cutoff, particularly in CKD and anemia (CKD: from 0.65; 95% CI, 0.57-0.72; to 0.83; 95% CI, 0.76-0.89; anemia: from 0.80; 95% CI, 0.76-0.84; to 0.86; 95% CI, 0.82-0.90), with consistent findings in the Roche cohort. In all biological subgroups, the double-cutoff strategy also increased accuracy relative to the single cutoff and reduced false classifications but yielded 12% to 39% intermediate results. When compared directly, the optimal cutoff provided higher accuracy than the double cutoff for CKD while lowering total diagnostic costs. For anemia, the double cutoff showed slightly higher accuracy but required confirmatory PET in up to 25% of cases, offsetting its economic advantage. In obes
{"title":"Plasma Phosphorylated Tau 217 Cutoffs for Amyloid Pathology and Kidney Function, Body Mass Index, and Anemia.","authors":"Jihwan Yun, Jungah Lee, Daeun Shin, Eun Hye Lee, Jun Pyo Kim, Hongki Ham, Yuna Gu, Min Young Chun, Sung Hoon Kang, Hee Jin Kim, Duk L Na, Ko Woon Kim, Si Eun Kim, Yeshin Kim, Jaeho Kim, Na-Yeon Jung, Yeo Jin Kim, Soo Hyun Cho, Jin San Lee, Seonghyeon Kim, Henrik Zetterberg, Kaj Blennow, Fernando Gonzalez-Ortiz, Nicholas J Ashton, Joel B Braunstein, Philip B Verghese, Tim West, Matthew R Meyer, Sang Won Seo, Hyemin Jang","doi":"10.1001/jamaneurol.2025.5530","DOIUrl":"10.1001/jamaneurol.2025.5530","url":null,"abstract":"<p><strong>Importance: </strong>Plasma phosphorylated p-tau 217 levels vary with biological factors such as kidney dysfunction, body mass index (BMI), and anemia. It remains unclear whether a biological subgroup-specific optimal cutoff or a double-cutoff strategy could enhance diagnostic accuracy and cost efficiency beyond the standard single cutoff.</p><p><strong>Objective: </strong>To compare the diagnostic and economic performance of 3 plasma p-tau217 classification strategies for detecting amyloid-β (Aβ) positivity: standard single cutoff, subgroup-specific optimal cutoff, and double cutoff.</p><p><strong>Design, setting, and participants: </strong>This cohort study was a multicenter cross-sectional study conducted from 2016 to 2023; analyses were completed in 2025. Participants were recruited from multiple memory clinics and community-based cohorts. All participants had amyloid positron emission tomography (PET) imaging, clinical evaluation, and p-tau217 testing with measures of estimated glomerular filtration rate (eGFR), BMI, and hemoglobin. Measurements of p-tau217 were made using UGOT Simoa and Roche Elecsys, and the %p-tau217 ratio was assessed using a tau multianalyte assay (C2N Diagnostics LLC).</p><p><strong>Exposures: </strong>Kidney function (chronic kidney disease [CKD], eGFR <60 mL/min/1.73 m2; advanced CKD, eGFR <45 mL/min/1.73 m2), underweight (BMI <18.5), obesity (BMI ≥27.5), and anemia (hemoglobin <12 g/dL in women, <13 g/dL in men).</p><p><strong>Main outcomes and measures: </strong>Plasma p-tau217 concentration; standard single cutoff, optimal cutoffs, and double cutoff for Aβ positivity (Centiloid ≥25.5); accuracy; and cost-effectiveness estimated from false-positive, false-negative, and confirmatory imaging costs.</p><p><strong>Results: </strong>A total of 2571 participants were analyzed with UGOT, 1578 with Roche, and 304 with the C2N %p-tau217 ratio. The mean (SD) age was similar across cohorts (71.3 [8.6] years in the UGOT cohort, 71.3 [8.5] years in the Roche cohort, and 71.8 [7.8] years in the C2N cohort); there were 1633 (63.5%), 1006 (63.8%), and 191 (62.8%) women and 938 (36.5%), 572 (36.2%), and 113 (37.2%) men, respectively. In the UGOT cohort, the optimal cutoff improved diagnostic accuracy compared with the standard single cutoff, particularly in CKD and anemia (CKD: from 0.65; 95% CI, 0.57-0.72; to 0.83; 95% CI, 0.76-0.89; anemia: from 0.80; 95% CI, 0.76-0.84; to 0.86; 95% CI, 0.82-0.90), with consistent findings in the Roche cohort. In all biological subgroups, the double-cutoff strategy also increased accuracy relative to the single cutoff and reduced false classifications but yielded 12% to 39% intermediate results. When compared directly, the optimal cutoff provided higher accuracy than the double cutoff for CKD while lowering total diagnostic costs. For anemia, the double cutoff showed slightly higher accuracy but required confirmatory PET in up to 25% of cases, offsetting its economic advantage. In obes","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":21.3,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12865699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105505","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 : 2026-02-02DOI: 10.1001/jamaneurol.2025.5496
Candice Maenza, Carolee J. Winstein, Terrence E. Murphy, Nick M. Kitchen, Jennifer Tanaka, Jisung Yuk, Rini Varghese, Robert L. Sainburg
Importance Ipsilesional upper-limb motor deficits after stroke are functionally important yet largely neglected in rehabilitation. Remediation may improve motor outcomes in individuals with severe contralesional arm hemiparesis. Objective To determine whether training of the ipsilesional arm improves motor performance in chronic stroke with severe contralesional impairment and significant ipsilesional arm motor deficits. Design, Setting, and Participants This 2-site, parallel-group randomized clinical trial with blinded outcome assessment was conducted from February 2019 to August 2024, with follow-up through 6 months posttreatment. Data analysis was performed from August 2024 through August 2025. The trial was conducted at outpatient research laboratories at Penn State College of Medicine and the University of Southern California among adults with radiologically confirmed unilateral middle cerebral artery stroke, severe contralesional upper-extremity impairment (Fugl-Meyer score ≤28), and ipsilesional motor deficits. Participants were randomly assigned with equal probability to 2 treatment groups and stratified by sex. Interventions Participants were randomized to a 5-week, 15-session intervention focused on either the ipsilesional (n = 25) or contralesional (n = 28) upper limb. The ipsilesional group received ipsilesional virtual reality and manipulation training; the contralesional group received dose-matched, best practice contralesional arm therapy. Main Outcomes and Measures The primary outcomes were ipsilesional motor performance (Jebsen-Taylor Hand Function Test [excluding writing]), functional independence (Barthel Index), contralesional impairment severity (Fugl-Meyer Assessment [Upper Extremity]), and perceived manual ability (ABILHAND-Stroke). Results Of 100 adults screened, 58 were included, and 53 participants (91%) completed both baseline and immediate posttreatment assessments. Of the 53 participants who completed the study, mean (SD) age was 59 (11) years, and 17 participants (32%) were female. In this modified intent-to-treat analysis, the ipsilesional treatment group showed significant improvement in Jebsen-Taylor Hand Function Test performance (mean difference, −5.87 seconds; 95% CI, −8.89 to −2.85 seconds; <jats:italic>P</jats:italic> = .003), representing a 12% reduction in time to completion. Relative to its own baseline, this improvement was sustained at the 3-week and 6-month follow-up times within the ipsilesional treatment group only. No significant effects were observed for the remaining outcomes. Conclusions and Relevance In this parallel-group randomized clinical trial, targeted ipsilesional arm training significantly improved ipsilesional motor performance in patients with chronic stroke with severe paresis. This approach may enhance functional capacity in patients who rely on the ipsilesional arm for daily activities. Trial Registration ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink="http://www.w3.org/19
卒中后同侧性上肢运动障碍在功能上很重要，但在康复中却被忽视。补救措施可以改善严重对侧性肢体偏瘫患者的运动预后。目的探讨同侧臂训练是否能改善慢性脑卒中伴严重对侧损伤和显著同侧臂运动障碍患者的运动能力。设计、环境和参与者本研究于2019年2月至2024年8月进行双中心、平行组随机临床试验，并进行盲法结局评估，治疗后随访6个月。数据分析从2024年8月到2025年8月进行。该试验在宾夕法尼亚州立医学院和南加州大学的门诊研究实验室进行，研究对象为影像学证实的单侧大脑中动脉卒中、严重对位性上肢损伤（fugel - meyer评分≤28）和同侧运动缺陷的成年人。参与者以等概率随机分为两个治疗组，并按性别分层。干预措施参与者被随机分配到一个5周，15个疗程的干预，重点是同侧上肢（n = 25）或对侧上肢（n = 28）。裸眼组接受裸眼虚拟现实及操作训练；对侧组接受剂量匹配、最佳做法的对侧臂治疗。主要结果和测量主要结果为同侧运动表现（Jebsen-Taylor手功能测试[不包括书写]）、功能独立性（Barthel指数）、对侧损伤严重程度（Fugl-Meyer评估[上肢]）和感知手能力（ABILHAND-Stroke）。结果在100名被筛选的成年人中，58名被纳入，53名参与者（91%）完成了基线和治疗后立即评估。在完成研究的53名参与者中，平均（SD）年龄为59（11）岁，17名参与者（32%）为女性。在这一改进的意向治疗分析中，同切除治疗组在捷成-泰勒手功能测试（Jebsen-Taylor Hand Function Test）方面表现出显著改善（平均差值为- 5.87秒；95% CI为- 8.89至- 2.85秒；P = 0.003），完成时间减少了12%。相对于自己的基线，这种改善仅在同切治疗组的3周和6个月随访时间内持续。其余结果未观察到显著影响。结论与意义在这项平行组随机临床试验中，有针对性的同侧手臂训练可显著改善慢性脑卒中伴重度瘫患者的同侧运动能力。这种方法可以提高依赖同侧臂进行日常活动的患者的功能能力。临床试验注册：ClinicalTrials.gov标识符：NCT03634397
{"title":"Targeted Remediation of the Ipsilesional Arm in Chronic Stroke","authors":"Candice Maenza, Carolee J. Winstein, Terrence E. Murphy, Nick M. Kitchen, Jennifer Tanaka, Jisung Yuk, Rini Varghese, Robert L. Sainburg","doi":"10.1001/jamaneurol.2025.5496","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5496","url":null,"abstract":"Importance Ipsilesional upper-limb motor deficits after stroke are functionally important yet largely neglected in rehabilitation. Remediation may improve motor outcomes in individuals with severe contralesional arm hemiparesis. Objective To determine whether training of the ipsilesional arm improves motor performance in chronic stroke with severe contralesional impairment and significant ipsilesional arm motor deficits. Design, Setting, and Participants This 2-site, parallel-group randomized clinical trial with blinded outcome assessment was conducted from February 2019 to August 2024, with follow-up through 6 months posttreatment. Data analysis was performed from August 2024 through August 2025. The trial was conducted at outpatient research laboratories at Penn State College of Medicine and the University of Southern California among adults with radiologically confirmed unilateral middle cerebral artery stroke, severe contralesional upper-extremity impairment (Fugl-Meyer score ≤28), and ipsilesional motor deficits. Participants were randomly assigned with equal probability to 2 treatment groups and stratified by sex. Interventions Participants were randomized to a 5-week, 15-session intervention focused on either the ipsilesional (n = 25) or contralesional (n = 28) upper limb. The ipsilesional group received ipsilesional virtual reality and manipulation training; the contralesional group received dose-matched, best practice contralesional arm therapy. Main Outcomes and Measures The primary outcomes were ipsilesional motor performance (Jebsen-Taylor Hand Function Test [excluding writing]), functional independence (Barthel Index), contralesional impairment severity (Fugl-Meyer Assessment [Upper Extremity]), and perceived manual ability (ABILHAND-Stroke). Results Of 100 adults screened, 58 were included, and 53 participants (91%) completed both baseline and immediate posttreatment assessments. Of the 53 participants who completed the study, mean (SD) age was 59 (11) years, and 17 participants (32%) were female. In this modified intent-to-treat analysis, the ipsilesional treatment group showed significant improvement in Jebsen-Taylor Hand Function Test performance (mean difference, −5.87 seconds; 95% CI, −8.89 to −2.85 seconds; <jats:italic>P</jats:italic> = .003), representing a 12% reduction in time to completion. Relative to its own baseline, this improvement was sustained at the 3-week and 6-month follow-up times within the ipsilesional treatment group only. No significant effects were observed for the remaining outcomes. Conclusions and Relevance In this parallel-group randomized clinical trial, targeted ipsilesional arm training significantly improved ipsilesional motor performance in patients with chronic stroke with severe paresis. This approach may enhance functional capacity in patients who rely on the ipsilesional arm for daily activities. Trial Registration ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/19","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"291 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101444","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 : 2026-02-02DOI: 10.1001/jamaneurol.2025.5412
Michael A. Williams, Mark G. Luciano, Jan Malm, Mark G. Hamilton
This Viewpoint describes the diagnosis and treatment history of normal pressure hydrocephalus and then highlights recent trial results that may serve as a catalyst for renewed scientific and clinical efforts.
{"title":"The Next Era of Idiopathic Normal Pressure Hydrocephalus","authors":"Michael A. Williams, Mark G. Luciano, Jan Malm, Mark G. Hamilton","doi":"10.1001/jamaneurol.2025.5412","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5412","url":null,"abstract":"This Viewpoint describes the diagnosis and treatment history of normal pressure hydrocephalus and then highlights recent trial results that may serve as a catalyst for renewed scientific and clinical efforts.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"36 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101451","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 : 2026-02-01DOI: 10.1001/jamaneurol.2025.4445
Kevin N Sheth, E Ray Dorsey, Michael S Okun
{"title":"Preventive Neurology Isn't a Pill; It's a Plan.","authors":"Kevin N Sheth, E Ray Dorsey, Michael S Okun","doi":"10.1001/jamaneurol.2025.4445","DOIUrl":"10.1001/jamaneurol.2025.4445","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"97-98"},"PeriodicalIF":21.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540748","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 : 2026-02-01DOI: 10.1001/jamaneurol.2025.5077
Wei Hu, Chunrong Tao, Rui Li, Zhongjun Chen, Wenhuo Chen, Tingyu Yi, Hao Wang, Peiyang Zhou, Zhihua Cao, Guoyong Zeng, Tao Cui, Junfeng Su, Li Chen, Guoping Wang, Jun Sun, Yuyou Zhu, Li Wang, Chao Zhang, Tianlong Liu, Jianlong Song, Xiaozhong Jing, Anmo Wang, Jinjing Wang, Pengfei Xu, Cong Luo, Adnan I Qureshi, Mohamad AbdalKader, Thanh N Nguyen, Jeffrey L Saver, Raul G Nogueira, Xinfeng Liu
<p><strong>Importance: </strong>Endovascular thrombectomy (EVT) has been established as an effective treatment for acute basilar artery occlusion (BAO) in the short term. However, the durability of these benefits over the long term has not been well characterized.</p><p><strong>Objective: </strong>To determine whether the clinical benefits of EVT for acute BAO are sustained at 3 years, with a primary focus on functional outcomes and mortality compared with best medical management alone.</p><p><strong>Design, setting, and participants: </strong>This study is a 3-year follow-up extension of a multicenter randomized clinical trial conducted between February 2021 and January 2022, with follow-up data collected through January 2025. The study was designed as an open-label, assessor-blinded trial to evaluate the long-term efficacy of EVT. The trial was conducted at 36 comprehensive stroke centers across China, representing a diverse, population-based setting that enhances the generalizability of the results. A total of 340 patients with acute BAO within 12 hours of estimated symptom onset were randomly assigned to the thrombectomy or control group. Eligible participants were adults with imaging-confirmed BAO and without contraindications to endovascular therapy. Of the randomized patients, 307 (90.3%) completed 3-year follow-up-203 in the thrombectomy group and 104 in the control group.</p><p><strong>Interventions: </strong>Participants in the thrombectomy group received EVT in combination with best medical management, while the control group received best medical management alone. EVT procedures were performed according to institutional protocols using stent retrievers, aspiration devices, balloon angioplasty, stent deployment, intra-arterial thrombolysis, or combinations of these approaches that were left to the discretion of the treating team.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was a modified Rankin Scale (mRS) score of 0 to 3 at 3 years, representing the ability to walk and perform self-care. Secondary outcomes included a mRS score of 0 to 2, distribution across the mRS score categories, and quality of life. These outcomes were prespecified prior to data analysis.</p><p><strong>Results: </strong>Among 307 patients (median [IQR] age, 68 [59-75]; 211 [69%] male) with available data, an mRS score of 0 to 3 at 3 years was observed in 78 patients (38.4%) in the thrombectomy group and in 19 patients (18.3%) in the control group (adjusted risk ratio, 2.05; 95% CI, 1.35-3.11; P = .001). The distribution of mRS scores favored the thrombectomy group over the control group (adjusted common odds ratio, 2.60; 95% CI, 1.53-4.43). The cumulative 3-year mortality increased from 36.7% (n = 83) at 90 days to 55.7% (n = 113) in the thrombectomy group and 55.3% (n = 63) to 73.1% (n = 76) in the control group (adjusted risk ratio, 0.76; 95% CI, 0.65-0.89). On prespecified subgroup analysis, benefit was observed in patients younger th
{"title":"Endovascular vs Medical Treatment of Basilar Artery Occlusion: 3-Year Outcomes of the ATTENTION Randomized Clinical Trial.","authors":"Wei Hu, Chunrong Tao, Rui Li, Zhongjun Chen, Wenhuo Chen, Tingyu Yi, Hao Wang, Peiyang Zhou, Zhihua Cao, Guoyong Zeng, Tao Cui, Junfeng Su, Li Chen, Guoping Wang, Jun Sun, Yuyou Zhu, Li Wang, Chao Zhang, Tianlong Liu, Jianlong Song, Xiaozhong Jing, Anmo Wang, Jinjing Wang, Pengfei Xu, Cong Luo, Adnan I Qureshi, Mohamad AbdalKader, Thanh N Nguyen, Jeffrey L Saver, Raul G Nogueira, Xinfeng Liu","doi":"10.1001/jamaneurol.2025.5077","DOIUrl":"10.1001/jamaneurol.2025.5077","url":null,"abstract":"<p><strong>Importance: </strong>Endovascular thrombectomy (EVT) has been established as an effective treatment for acute basilar artery occlusion (BAO) in the short term. However, the durability of these benefits over the long term has not been well characterized.</p><p><strong>Objective: </strong>To determine whether the clinical benefits of EVT for acute BAO are sustained at 3 years, with a primary focus on functional outcomes and mortality compared with best medical management alone.</p><p><strong>Design, setting, and participants: </strong>This study is a 3-year follow-up extension of a multicenter randomized clinical trial conducted between February 2021 and January 2022, with follow-up data collected through January 2025. The study was designed as an open-label, assessor-blinded trial to evaluate the long-term efficacy of EVT. The trial was conducted at 36 comprehensive stroke centers across China, representing a diverse, population-based setting that enhances the generalizability of the results. A total of 340 patients with acute BAO within 12 hours of estimated symptom onset were randomly assigned to the thrombectomy or control group. Eligible participants were adults with imaging-confirmed BAO and without contraindications to endovascular therapy. Of the randomized patients, 307 (90.3%) completed 3-year follow-up-203 in the thrombectomy group and 104 in the control group.</p><p><strong>Interventions: </strong>Participants in the thrombectomy group received EVT in combination with best medical management, while the control group received best medical management alone. EVT procedures were performed according to institutional protocols using stent retrievers, aspiration devices, balloon angioplasty, stent deployment, intra-arterial thrombolysis, or combinations of these approaches that were left to the discretion of the treating team.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was a modified Rankin Scale (mRS) score of 0 to 3 at 3 years, representing the ability to walk and perform self-care. Secondary outcomes included a mRS score of 0 to 2, distribution across the mRS score categories, and quality of life. These outcomes were prespecified prior to data analysis.</p><p><strong>Results: </strong>Among 307 patients (median [IQR] age, 68 [59-75]; 211 [69%] male) with available data, an mRS score of 0 to 3 at 3 years was observed in 78 patients (38.4%) in the thrombectomy group and in 19 patients (18.3%) in the control group (adjusted risk ratio, 2.05; 95% CI, 1.35-3.11; P = .001). The distribution of mRS scores favored the thrombectomy group over the control group (adjusted common odds ratio, 2.60; 95% CI, 1.53-4.43). The cumulative 3-year mortality increased from 36.7% (n = 83) at 90 days to 55.7% (n = 113) in the thrombectomy group and 55.3% (n = 63) to 73.1% (n = 76) in the control group (adjusted risk ratio, 0.76; 95% CI, 0.65-0.89). On prespecified subgroup analysis, benefit was observed in patients younger th","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"107-114"},"PeriodicalIF":21.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12750332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145856499","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}
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