JAMA neurology最新文献

{"title":"Sex Differences in P-Tau217, Tau Aggregation, and Cognitive Decline.","authors":"Gillian T Coughlan, Valentin Ourry, Diana Townsend, Hannah Klinger, Jane A Brown, Madison Cuppels, Tobey Betthauser, Rebecca Langhough, Karly Cody, Mabel Seto, Colin Birkenbihl, Annie Li, Michelle Farrell, Emma Thibault, Pia Kivisäkk Webb, Steven Arnold, Robert A Rissman, Michael Properzi, Aaron Schultz, Keith Johnson, Oliver Langford, Michael C Donohue, Sylvia Villeneuve, Sterling C Johnson, Hyun-Sik Yang, JoAnn E Manson, Reisa Sperling, Rachel F Buckley","doi":"10.1001/jamaneurol.2025.5670","DOIUrl":"10.1001/jamaneurol.2025.5670","url":null,"abstract":"<p><strong>Importance: </strong>Among individuals with high levels of amyloid-β (Aβ), women exhibit higher insoluble tau burden and accumulation than age-matched men. It remains unclear whether this sex difference is influenced by soluble phosphorylated tau (p-tau), a biomarker that changes early in Alzheimer disease.</p><p><strong>Objective: </strong>To investigate whether sex and aggregated Aβ synergistically predict plasma phosphorylated tau 217 (p-tau217) levels and whether levels of p-tau217 predict cross-sectional and longitudinal tau aggregation in a sex-specific manner (as measured by positron emission tomography [PET]).</p><p><strong>Design, setting, and participants: </strong>This longitudinal study analyzed data between September 7, 2024, and October 29, 2025, from 1 clinical trial cohort and 4 observational study cohorts including men and women without cognitive impairment who had undergone multiple assessments via tau PET (18F-flortaucipir or 18F-MK-6240) and plasma p-tau217 assay at baseline. Cognitive performance was measured with the Preclinical Alzheimer Cognitive Composite. Data on cognitive performance were available from 3 of the 5 cohorts for a mean of 4.6 years (SD, 3.1 years). Across the 5 cohorts, the mean follow-up for tau PET was 3.6 years (SD, 1.7 years).</p><p><strong>Exposures: </strong>Self-reported sex (male or female), tau PET, and p-tau217 assay.</p><p><strong>Main outcomes and measures: </strong>The primary analyses used linear and mixed-effects models to assess baseline and longitudinal sex × p-tau217 interactions for 9 tau PET regions. The secondary analyses assessed sex × p-tau217 interactions for cognitive change using the Preclinical Alzheimer Cognitive Composite.</p><p><strong>Results: </strong>Across the 5 cohorts, there were a total of 1292 participants (63.6% women; mean age, 70.6 [SD, 6.4] years) with tau PET assessments. Compared with men, women had significantly higher baseline p-tau217 levels at higher aggregated Aβ Centiloid levels (β, -0.21 [95% CI, -0.37 to -0.05], P = .009; highest interaction was found in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration [A4/LEARN] cohort). The sex × p-tau217 interactions at baseline were significant for 1 tau PET region in the Harvard Aging Brain Study (HABS) cohort, for 2 tau PET regions in the A4/LEARN cohort, for 6 tau PET regions in the Wisconsin Registry of Alzheimer's Prevention (WRAP) cohort, and for 4 tau PET regions in the Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) cohort. Longitudinal interactions were significant for 4 tau PET regions in the A4/LEARN cohort, for 5 tau PET regions in both the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort and the WRAP cohort, and for 2 PET regions in both the HABS cohort and the PREVENT-AD cohort. Compared with men, women displayed greater tau deposition and accumulation at high","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"369-381"},"PeriodicalIF":21.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12910460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201673","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}

{"title":"Timing and Location in Minimally Invasive ICH Surgery.","authors":"Yun-Xiang Zhou, Guo-Bin Zhang","doi":"10.1001/jamaneurol.2026.0148","DOIUrl":"10.1001/jamaneurol.2026.0148","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"407"},"PeriodicalIF":21.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catheter Ablation and Oral Anticoagulation for Secondary Stroke Prevention in Atrial Fibrillation: The STABLED Randomized Clinical Trial.","authors":"Kazumi Kimura, Yasuhiro Nishiyama, Yu-Ki Iwasaki, Wataru Shimizu, Kazunori Toyoda, Yuki Sakamoto, Takehiro Katano, Teppei Yamamoto, Masataka Takeuchi, Kenta Kumagai, Kazuma Tsuto, Kaoru Sugi, Kengo Kusano, Masatoshi Koga, Seiji Okubo, Takahiro Sato, Hirotoshi Hamaguchi, Akihiro Yoshida, Ayako Kuriki, Kaoru Tanno, Kazuo Kitagawa, Nobuhisa Hagiwara, Hiroyuki Daida, Yasuyuki Iguchi, Shigeru Fujimoto, Susumu Miyamoto, Masayuki Fukuzawa, Masako Sugimoto, Atsushi Takita, Toshiaki Otsuka, Ken Okumura","doi":"10.1001/jamaneurol.2026.0155","DOIUrl":"10.1001/jamaneurol.2026.0155","url":null,"abstract":"<p><strong>Importance: </strong>Among patients with atrial fibrillation, those with a recent stroke are at significantly higher risk of recurrence than those without. Catheter ablation is expected to reduce the risk of recurrent stroke, heart failure, and mortality in these patients.</p><p><strong>Objective: </strong>To evaluate the efficacy and safety of catheter ablation added to standard therapy for reducing the risk of recurrent stroke or composite outcomes in patients with atrial fibrillation and a recent history of stroke.</p><p><strong>Design, setting, and participants: </strong>The Stroke Secondary Prevention With Catheter Ablation and Edoxaban for Patients With Nonvalvular Atrial Fibrillation (STABLED) study was an open-label, parallel-group, randomized clinical trial. Patients were enrolled from January 2018 to March 2021 and observed until March 2024. This study was conducted at 45 sites in Japan. Patients aged 20 years or older and 85 years or younger and those with a definitive diagnosis of nonvalvular atrial fibrillation on electrocardiogram, a history of ischemic stroke, currently receiving or scheduled to receive edoxaban, and having a modified Rankin Scale score of 3 or less were enrolled. Study data were analyzed from September 2024 to July 2025.</p><p><strong>Interventions: </strong>Patients were randomized to receive standard therapy or standard therapy plus catheter ablation (after ≥4 weeks of edoxaban, within 1-6 months of index stroke onset).</p><p><strong>Main outcomes and measures: </strong>The primary end point was a composite of recurrent ischemic stroke, systemic embolism, all-cause death, and hospitalization for heart failure. Safety related to the catheter ablation procedure was assessed.</p><p><strong>Results: </strong>A total of 251 patients were enrolled and 249 (mean [SD] age, 71.7 [7.5] years; 187 male [75.1%]) were randomized (standard therapy, 124; standard therapy plus catheter ablation, 125). Median follow-up was greater than 3 years. The primary end point occurred at rates of 4.9% and 5.6% per person-year (hazard ratio, 1.11; 95% CI, 0.62-2.01) with standard therapy vs catheter ablation, respectively. The respective mortality rates were 1.0 and 2.8 per 100 person-years. Two ablation-related adverse events (cardiac tamponade, stroke) were reported (0.8% each).</p><p><strong>Conclusions and relevance: </strong>In patients with atrial fibrillation and a recent stroke history, standard therapy plus catheter ablation did not significantly reduce the risk of the primary composite end point. The observed event rate was lower than anticipated, suggesting that the study was underpowered to detect clinically meaningful differences.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT03777631.</p>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"329-338"},"PeriodicalIF":21.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325899","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}

{"title":"Association Between GLP-1 RAs and Idiopathic Intracranial Hypertension.","authors":"Luis Manzano-Hernández, M Millán Vázquez, David León-Jiménez","doi":"10.1001/jamaneurol.2026.0001","DOIUrl":"10.1001/jamaneurol.2026.0001","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"406"},"PeriodicalIF":21.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing and Location in Minimally Invasive ICH Surgery-Reply.","authors":"Adam S Arthur, David J Fiorella","doi":"10.1001/jamaneurol.2026.0145","DOIUrl":"10.1001/jamaneurol.2026.0145","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"408"},"PeriodicalIF":21.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"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":"10.1001/jamaneurol.2025.5625","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To compare effectiveness and safety of brivaracetam, cenobamate, lacosamide, and perampanel as adjunctive therapies in adults with drug-resistant focal epilepsy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposures: &lt;/strong&gt;Add-on treatment with brivaracetam, cenobamate, lacosamide, or perampanel.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;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 &lt; .001), perampanel (OR, 0.26; 95% CI, 0.16-0.42; P &lt; .001), and lacosamide (OR, 0.29; 95% CI, 0.17-0.49; P &lt; .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 &lt; .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).&lt;/p&gt;&lt;p&gt;&lt;stron","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"320-328"},"PeriodicalIF":21.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12887838/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five Years of Ublituximab in Multiple Sclerosis: ULTIMATE I and II Open-Label Extension Study.","authors":"Bruce A C Cree, Edward Fox, Hans-Peter Hartung, Enrique Alvarez, Peiqing Qian, Sibyl Wray, Derrick Robertson, Krzysztof Selmaj, Daniel Wynn, Koby Mok, Chris Rowland, Karthik Bodhinathan, Peter Sportelli, Hari P Miskin, Lawrence Steinman","doi":"10.1001/jamaneurol.2026.0007","DOIUrl":"10.1001/jamaneurol.2026.0007","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;In the 2-year Study to Assess the Efficacy and Safety of Ublituximab in Participants With Relapsing Forms of Multiple Sclerosis (ULTIMATE) I and II randomized clinical studies, disease activity was significantly reduced with ublituximab vs teriflunomide in participants with relapsing multiple sclerosis (RMS).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To evaluate long-term ublituximab clinical efficacy and safety.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;The 2-year, multicenter, randomized, active-controlled, double-blind period (DBP) of the ULTIMATE I and II phase 3 studies occurred September 2017 to November 2020. Enrollment in the ongoing ULTIMATE open-label extension (OLE) study began November 2019; data cutoff for this analysis was January 1, 2024.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Intervention: &lt;/strong&gt;ULTIMATE OLE participants continued ublituximab (UBL-UBL) or switched from teriflunomide to ublituximab (TER-UBL).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;Efficacy (annualized relapse rate [ARR], 24-week confirmed disability progression [CDP24], and 24-week confirmed disability improvement [CDI24]) and safety were key outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of 985 adults with RMS who completed ULTIMATE I and II, 851 enrolled in the ULTIMATE OLE and were included in the analysis. On DBP completion, more than 85% of participants (UBL-UBL, 422 of 494; TER-UBL, 429 of 491) entered the OLE, of whom more than 70% (UBL-UBL, 297 of 422; TER-UBL, 327 of 429) continued taking ublituximab at year 5 (OLE year 3) at data cutoff, making up the analysis population (mean [SD] age, 38.5 [9.7] years; 532 female [62.5%]). TER-UBL participants experienced a 58.4% ARR reduction at 1 year after the switch (0.182 vs 0.076; rate ratio, 0.42; 95% CI, 0.29-0.60; P &lt; .001), and ARR continued to decrease to 0.048 (year 4) and 0.045 (year 5). UBL-UBL participants had further ARR reductions after the DBP (0.053, 0.032, and 0.020 for years 3, 4, and 5, respectively). At year 5, CDP24 was 8.0% in UBL-UBL participants vs 14.3% in TER-UBL participants (P = .01), and CDI24 was 17.0% in UBL-UBL participants vs 12.2% in TER-UBL participants (P = .02). Adverse events were consistent with the established safety profile from pivotal trials, with exposure-adjusted incidence rates per 100 participant-years of serious infections (excluding COVID events) of 2.10 (UBL-UBL) and 2.58 (TER-UBL). On average, immunoglobulin levels remained above the lower limit of normal, and no significant differences in serious infection rates were observed regardless of immunoglobulin level.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;Results reveal that sustained clinical benefits were observed with 5 years of ublituximab treatment: ARR in year 5 showed 1 relapse per 50 participant-years of ublituximab treatment and 92% of UBL-UBL participants remained free from CDP24. Results confirm long-term ublituximab benefits and early initiation of high-efficacy treatment.&lt;/","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"348-358"},"PeriodicalIF":21.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12910456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201676","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}

{"title":"Long-Term Outcomes and Recovery Trajectories in Out-of-Hospital Cardiac Arrest: A 2-Year Follow-Up of the Randomized Clinical TTM2 Trial.","authors":"Malin Hultgren, Erik Blennow Nordström, Susann Ullén, Niklas Nielsen, Josef Dankiewicz, Janus Christian Jakobsen, Katarina Heimburg, Marion Moseby-Knappe, Jan Belohlávek, Mattias Bohm, Alain Cariou, Glenn Eastwood, Hans Friberg, Anders M Grejs, Naomi Hammond, Matthias Hänggi, Juraj Hrecko, Manuela Iten, Thomas R Keeble, Christoph Leithner, Helena Levin, Marco Mion, Christian Rylander, Claudia Schrag, Matthew Thomas, Matt P Wise, Paul Young, Tobias Cronberg, Gisela Lilja","doi":"10.1001/jamaneurol.2025.5614","DOIUrl":"10.1001/jamaneurol.2025.5614","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Guidelines for temperature control following out-of-hospital cardiac arrest (OHCA) are based on trials with end points of 180 days or fewer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To investigate if targeted hypothermia, compared with targeted normothermia with early treatment of fever, affects functional outcome focusing on societal participation or cognitive functioning at 24 months in initially comatose OHCA survivors. An additional objective was to explore recovery trajectories up to 24 months post arrest.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;The randomized clinical Targeted Hypothermia vs Targeted Normothermia After OHCA (TTM2) trial (November 2017-2020) included blinded follow-up at 1, 6, and 24 months post randomization (December 2017-June 2022), with analyses performed in 2024. TTM2 was an international, multicenter study conducted at 61 hospitals in 14 countries. The study included 1861 adults with OHCA of presumed cardiac or unknown cause who were initially comatose. There were 992 survivors at 1 month, 943 at 6 months, and 835 at 24 months. Nonparticipation rates at follow-up were 44 (4%), 107 (11%), and 165 (20%), respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Intervention: &lt;/strong&gt;Participants were randomized 1:1 to undergo temperature control via targeted hypothermia (33 °C) or targeted normothermia and early treatment of fever (≥37.8 °C).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;The functional outcome, including societal participation, was assessed using the Glasgow Outcome Scale-Extended (GOSE). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities Test (SDMT).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of the participants who were followed up, 84% were male, with a mean (SD) age of 60 (14) years, and clinical variables were similar between the hypothermia and normothermia temperature groups. No significant differences were found between temperature groups regarding societal participation (GOSE: odds ratio, 0.97 [95% CI, 0.72-1.30]) or cognitive function (MoCA: mean difference, -0.02 [95% CI, -0.67 to 0.63]; SDMT: mean difference, -0.09 [95% CI, -0.33 to 0.16]) at 24 months. Improvement for GOSE was significant within the first 6 months (1 to 6 months: n = 1707 [95% CI, -2.00 to -1.50]; P &lt; .001; 6 to 24 months: n = 1606 [95% CI, -0.50 to &lt;0.001]; P = .10). Intraindividual improvement and decline corresponding to thresholds for minimal important differences were observed for societal participation and cognitive function up to 24 months.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;Targeted hypothermia, compared with targeted normothermia, did not affect societal participation or cognitive function at 24 months, suggesting no longer-term effect of hypothermia for the explored outcomes. The intraindividual changes observed indicate variability in recovery.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration: &lt;/strong&gt;ClinicalTrials.gov Identifier: NCT02908308.&lt;/","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"339-347"},"PeriodicalIF":21.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12910457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201663","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}

{"title":"Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial.","authors":"Ariel G Gildengers, Tamer S Ibrahim, Stewart J Anderson, James E Emanuel, Tales Santini, Jihui L Diaz, Brian J Lopresti, Sarah K Royse, Oscar L Lopez, Xuemei Zeng, Bruno de Almeida, Salem K Alkhateeb, Cong Chu, Thomas K Karikari, Laisze Lee, Andrea M Weinstein, Meryl A Butters","doi":"10.1001/jamaneurol.2026.0072","DOIUrl":"10.1001/jamaneurol.2026.0072","url":null,"abstract":"<p><strong>Importance: </strong>Lithium deficiency may contribute to Alzheimer disease pathogenesis. No randomized clinical trial has examined lithium's effects on cognition, neuroimaging, and plasma biomarkers in mild cognitive impairment (MCI).</p><p><strong>Objective: </strong>To examine the feasibility, safety, and preliminary efficacy of lithium carbonate for delaying cognitive decline in older adults with MCI.</p><p><strong>Design, setting, and participants: </strong>This single-site, randomized, double-blind, placebo-controlled pilot feasibility clinical trial was conducted at the University of Pittsburgh School of Medicine from February 2018 to August 2024, with 2-year follow-up. Analyses used linear mixed-effects models in the intention-to-treat population. Adults aged 60 years or older with MCI who were free of major psychiatric or neurologic illness and contraindications to lithium were included. Of 170 individuals assessed, 83 were randomized (41 lithium vs 42 placebo), with 80 starting treatment (41 lithium vs 39 placebo). Data were analyzed from August 2024 to December 2025.</p><p><strong>Intervention: </strong>Daily low-dose lithium carbonate or placebo for 2 years.</p><p><strong>Main outcomes and measures: </strong>Six prespecified coprimary outcomes included cognitive performance (California Verbal Learning Test-II [CVLT-II] delayed recall, Brief Visuospatial Memory Test-Revised, preclinical Alzheimer cognitive composite), hippocampal volume, cortical gray matter volume, and brain-derived neurotrophic factor.</p><p><strong>Results: </strong>Among 80 participants (mean [SD] age, lithium: 72.93 [8.77] years; placebo: 71.22 [6.47] years; 56% female), none of the 6 coprimary outcomes met the prespecified significance threshold. Mean (SD) CVLT-II baseline scores were 7.95 (3.4) for lithium and 7.90 (3.9) for placebo; scores declined 1.42 points annually in the placebo group vs 0.73 points in the lithium group (difference, 0.69 points per year; 95% CI, 0.01-1.37; P = .05). Hippocampal and cortical volumes showed a decline over time in both groups, but no significant treatment × time interactions. Serious adverse events occurred in 12 of 41 (29%) receiving lithium vs 9 of 39 (23%) receiving placebo; none were definitely treatment related. One death occurred in the placebo group. Common adverse events included increased creatinine levels (12 of 41 [29%] with lithium vs 12 of 39 [31%] with placebo), diarrhea (12 of 41 [29%] vs 6 of 39 [15%]), tiredness (12 of 41 [29%] vs 6 of 39 [15%]), and tremor occurrence (10 of 41 [24%] vs 6 of 39 [15%]).</p><p><strong>Conclusions and relevance: </strong>This pilot randomized clinical trial established feasibility, confirmed safety and tolerability, and generated effect size estimates for future trials of low-dose lithium in MCI. None of the coprimary outcomes met the prespecified significance threshold.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT03185208.</p>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"310-319"},"PeriodicalIF":21.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325882","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}

{"title":"Clarification to Table 3.","authors":"","doi":"10.1001/jamaneurol.2026.0675","DOIUrl":"10.1001/jamaneurol.2026.0675","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"83 4","pages":"408"},"PeriodicalIF":21.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673502","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}