JAMA neurology最新文献

{"title":"Risk of Poststroke Epilepsy Among Young Adults With Ischemic Stroke or Intracerebral Hemorrhage","authors":"Esmée Verburgt, Lina Fellah, Merel S. Ekker, Mijntje M. I. Schellekens, Esther M. Boot, Maikel H. M. Immens, Mayte E. van Alebeek, Paul J. A. M. Brouwers, Renate M. Arntz, Gert W. van Dijk, Rob A. R. Gons, Inge W. M. van Uden, Tom den Heijer, Julia H. van Tuijl, Karlijn F. de Laat, Anouk G.W. van Norden, Sarah E. Vermeer, Marian S. G. van Zagten, Robert J. van Oostenbrugge, Marieke J. H. Wermer, Paul J. Nederkoorn, Henk Kerkhoff, Fergus A. Rooyer, Frank G. van Rooij, Ido R. van den Wijngaard, Anil M. Tuladhar, Jamie I. Verhoeven, Nina A. Hilkens, Frank-Erik de Leeuw","doi":"10.1001/jamaneurol.2025.0465","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0465","url":null,"abstract":"ImportancePoststroke epilepsy (PSE) is a major complication among young adults and is associated with problems with functional recovery and daily life. Although scores have been developed to predict risk of PSE, they have not been validated among patients with stroke at a young age.ObjectivesTo investigate both the risk of and risk factors for PSE at a young age and validate current PSE risk scores among a cohort of young adults.Design, Setting, and ParticipantsThis cohort study used data from ODYSSEY (Observational Dutch Young Symptomatic Stroke Study), a prospective cohort study conducted among 17 hospitals in the Netherlands between May 27, 2013, and March 3, 2021, with follow-up until February 28, 2024. Participants included 1388 consecutive patients aged 18 to 49 years with neuroimaging-proven ischemic stroke or intracerebral hemorrhage (ICH) and without a history of epilepsy. Statistical analysis took place between June and August 2024.ExposureFirst-ever neuroimaging-proven ischemic stroke or ICH.Main Outcomes and MeasuresPoststroke epilepsy was defined as at least 1 remote symptomatic seizure (>7 days). Cumulative incidence functions were used to calculate the 5-year risk of PSE. Fine-Gray regression models were used to identify risk factors associated with PSE (age, sex, clinical stroke, and neuroimaging variables). The performances of the SeLECT (severity of stroke, large-artery atherosclerosis, early seizure, cortical involvement, and territory of middle cerebral artery) 2.0 risk score (for ischemic stroke) and the CAVE (cortical involvement, age, bleeding volume, and early seizure) risk score (for ICH) were assessed with C statistics and calibration bar plots.ResultsThis study included 1388 patients (ischemic stroke, 1231 [88.7%]; ICH, 157 [11.3%]; median age, 44.1 years [IQR, 38.0-47.4 years]; 736 men [53.0%]; median follow-up, 5.3 years [IQR, 3.4-7.4 years]), of whom 57 (4.1%) developed PSE. The 5-year cumulative risk of PSE was 3.7% (95% CI, 0.2%-4.8%) after ischemic stroke and 7.6% (95% CI, 3.5%-11.8%) after ICH. Factors associated with PSE after ischemic stroke were an acute symptomatic seizure (<7 days) (hazard ratio [HR], 10.83 [95% CI, 2.05-57.07]; <jats:italic>P</jats:italic> = .005) and cortical involvement (HR, 5.35 [95% CI, 1.85-15.49]; <jats:italic>P</jats:italic> = .002). The only factor associated with PSE after ICH was cortical involvement (HR, 8.20 [95% CI, 2.22-30.25]; <jats:italic>P</jats:italic> = .002). The C statistic was 0.78 (95% CI, 0.71-0.84) for the SeLECT 2.0 risk score and 0.83 (95% CI, 0.76-0.90) for the CAVE risk score, and calibration was good for both scores.ConclusionThis study suggests that the risk of PSE among young adults is relatively low and that the factors that were associated with PSE were similar to variables included in the existing risk scores, which can therefore also be applied for young adults after stroke. Future clinical trials should investigate the optimal prima","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"26 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827725","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":"Standardized Definition of Progression Independent of Relapse Activity (PIRA) in Relapsing-Remitting Multiple Sclerosis.","authors":"Jannis Müller,Sifat Sharmin,Johannes Lorscheider,Serkan Ozakbas,Rana Karabudak,Dana Horakova,Bianca Weinstock-Guttman,Vahid Shaygannejad,Masoud Etemadifar,Raed Alroughani,Francesco Patti,Sara Eichau,Alexandre Prat,Alessandra Lugaresi,Valentina Tomassini,Allan G Kermode,Maria Pia Amato,Recai Turkoglu,Ayse Altintas,Katherine Buzzard,Aysun Soysal,Anneke van der Walt,Helmut Butzkueven,Yolanda Blanco,Oliver Gerlach,Samia J Khoury,Michael Barnett,Nevin John,Jeannette Lechner-Scott,Matteo Foschi,Andrea Surcinelli,Vincent van Pesch,Julie Prevost,Maria Jose Sa,Davide Maimone,Marie D'hooghe,Stella Hughes,Suzanne Hodgkinson,Chris McGuigan,Elisabetta Cartechini,Bruce Taylor,Daniele Spitaleri,Mark Slee,Pamela McCombe,Bassem Yamout,Pascal Benkert,Jens Kuhle,Ludwig Kappos,Izanne Roos,Tomas Kalincik,,Eva Kubala Havrdova,Marc Girard,Pierre Duquette,Marzena Fabis-Pedrini,William M Carroll,Olga Skibina,Riadh Gouider,Saloua Mrabet,Cristina Ramo-Tello,Claudio Solaro,Mario Habek,Bart Van Wijmeersch,Radek Ampapa,Richard Macdonell,Celia Oreja-Guevara,Koen de Gans,Guy Laureys,Jiwon Oh,Justin Garber,Orla Gray,Eduardo Agüera-Morales,Jose Luis Sanchez-Menoyo,Tamara Castillo-Triviño,Nikolaos Grigoriadis,Thor Petersen,Todd A Hardy,Steve Vucic,Stephen Reddel,Sudarshini Ramanathan,Abdullah Al-Asmi,Mihaela Simu,Seyed Mohammad Baghbanian,Dieter Poehlau,Talal Al-Harbi,Juan Ignacio Rojas,Norma Deri,Patrice Lalive,Melissa Cambron,Tunde Csepany,Neil Shuey,Barbara Willekens,Cameron Shaw,Danny Decoo,Jennifer Massey,Özgür Yaldizli,Tobias Derfuss,Cristina Granziera","doi":"10.1001/jamaneurol.2025.0495","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0495","url":null,"abstract":"ImportanceProgression independent of relapse activity (PIRA) is a significant contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (MS). Prior studies have used varying PIRA definitions, hampering the comparability of study results.ObjectiveTo compare various definitions of PIRA.Design, Setting, and ParticipantsThis cohort study involved a retrospective analysis of prospectively collected data from the MSBase registry from July 2004 to July 2023. The participants were patients with MS from 186 centers across 43 countries who had clinically definite relapsing-remitting MS, a complete minimal dataset, and 3 or more documented Expanded Disability Status Scale (EDSS) assessments.ExposureThree-hundred sixty definitions of PIRA as combinations of the following criteria: baseline disability (fixed baseline with re-baselining after PIRA, or plus re-baselining after relapses, or plus re-baselining after improvements), minimum confirmation period (6, 12, or 24 months), confirmation magnitude (EDSS score at/above worsening score or at/above threshold compared with baseline), freedom from relapse at EDSS score worsening (90 days prior, 90 days prior and 30 days after, 180 days prior and after, since previous EDSS assessment, or since baseline), and freedom from relapse at confirmation (30 days prior, 90 days prior, 30 days before and after, or between worsening and confirmation).Main Outcome and MeasureFor each definition, we quantified PIRA incidence and persistence (ie, absence of a 3-month confirmed EDSS improvement over ≥5 years).ResultsAmong 87 239 patients with MS, 33 303 patients fulfilled the inclusion criteria; 24 152 (72.5%) were female and 9151 (27.5%) were male. At the first visits, the mean (SD) age was 36.4 (10.9) years; 28 052 patients (84.2%) had relapsing-remitting MS, and the median (IQR) EDSS score was 2.0 (1.0-3.0). Participants had a mean (SD) 15.1 (11.9) visits over 8.9 (5.2) years. PIRA incidence ranged from 0.141 to 0.658 events per decade and persistence from 0.753 to 0.919, depending on the definition. In particular, the baseline and confirmation period influenced PIRA detection. The following definition yielded balanced incidence and persistence: a significant disability worsening compared with a baseline (reset after each PIRA event, relapse, and EDSS score improvement), in absence of relapses since the last EDSS assessment, confirmed with EDSS scores (not preceded by relapses within 30 days) that remained above the worsening threshold for at least 12 months.Conclusion and RelevanceIncidence and persistence of PIRA are determined by the definition used. The proposed standardized definition aims to enhance comparability among studies.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"121 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831613","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":"The Risk of Alzheimer Disease in APOE4 Homozygotes.","authors":"Eric M Reiman,Valentina Ghisays,Jessica B Langbaum","doi":"10.1001/jamaneurol.2025.0639","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0639","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"40 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831615","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":"Risk Factors Associated With Late-Onset Epilepsy in Dementia and Mild Cognitive Impairment","authors":"Ifrah Zawar, Mark Quigg, Emily L. Johnson, Soutik Ghosal, Carol Manning, Jaideep Kapur","doi":"10.1001/jamaneurol.2025.0552","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0552","url":null,"abstract":"ImportanceThe risk of developing epilepsy substantially increases after the age of 60 years (late-onset epilepsy [LOE]), particularly in people with cognitive decline ([PWCD] ie, dementia and/or mild cognitive impairment). Epilepsy is associated with worse cognitive and mortality outcomes in PWCD. Identifying PWCD at risk for developing LOE can facilitate early screening and treatment of epilepsy.ObjectiveTo investigate factors associated with LOE in PWCD.Design, Setting, and ParticipantsThis longitudinal, multicenter study is based on participants from 39 US Alzheimer’s Disease Research Centers from September 2005 through December 2021. Of 44 713 participants, 25 119 PWCD were identified. Of these, 14 685 were included who did not have epilepsy at enrollment, had 2 or more visits, and were 60 years or older at the most recent follow-up.ExposureThe association between various factors and LOE development in PWCD was investigated.Main Outcomes and MeasuresThe primary outcome was LOE, defined as seizures starting at or after 60 years of age. Those who did not develop LOE but were 60 years or older at follow-up served as controls. A multivariable Cox regression analysis assessed the association between various factors and LOE. Independent variables included age, sex, and socioeconomic factors (education, race, ethnicity), cardiovascular risks (hypertension, diabetes, hyperlipidemia), cerebrovascular disease (stroke or history of transient ischemic attack [TIA]), other neurologic comorbidities (Parkinson disease [PD], traumatic brain injury), cognition (age at dementia onset, dementia severity, type of dementia [Alzheimer disease (AD) vs non–AD]), genetics (apolipoprotein E4 [<jats:italic>APOE4</jats:italic>] status), lifestyle (alcohol misuse, smoking), and depression.ResultsOf the 14 685 participants (7355 female [50%] and 7330 male [50%]; mean [SD] age, 73.8 [8.5] years) who met the inclusion criteria, 221 participants (1.5%) developed LOE during follow-up. After adjusting for demographics, cardiovascular risks, neurologic comorbidities, genetics, cognitive factors, and depression, the following were associated with a higher risk of developing LOE: <jats:italic>APOE4</jats:italic> allele (adjusted hazard ratio [aHR], 1.39; 95% CI, 1.04-1.86; <jats:italic>P</jats:italic> = .03), dementia onset before age 60 years (aHR, 2.46; 95% CI, 1.53-3.95; <jats:italic>P</jats:italic> < .001), worse cognition (aHR, 2.35; 95% CI, 1.97-2.79; <jats:italic>P</jats:italic> < .001), AD dementia subtype (aHR, 1.68; 95% CI, 1.13-2.49; <jats:italic>P</jats:italic> = .01), stroke/TIA (aHR, 2.03; 95% CI, 1.37-3.01; <jats:italic>P</jats:italic> < .001), and PD (aHR, 2.53; 95% CI, 1.08-5.95; <jats:italic>P</jats:italic> = .03). In sensitivity analysis, using an alternative LOE definition of epilepsy onset after age 65 years revealed the same factors associated with LOE.Conclusion and RelevanceThis study showed that the <jats:italic>APOE4</jat","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"17 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827729","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":"Tongue Myokymia in IgLON5-IgG Autoimmunity","authors":"Shemonti Hasan, Divyanshu Dubey, Allen Aksamit","doi":"10.1001/jamaneurol.2025.0523","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0523","url":null,"abstract":"This case report discusses a man who tested positive for IgLON5-IgG antibody after intermittent episodes of paresthetic feeling involving the throat and jaw, associated with subtle dysarthria and dysphagia, and upper-extremity paresthesia with piloerection of the forearms.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"6 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827728","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":"Risk of Dementia in Individuals With Emergency Department Visits or Hospitalizations Due to Cannabis","authors":"Daniel T. Myran, Michael Pugliese, Lyndsay D. Harrison, Nathan M. Stall, Colleen Webber","doi":"10.1001/jamaneurol.2025.0530","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0530","url":null,"abstract":"ImportanceCannabis use is associated with short-term memory impairment and long-term changes in brain structure; however, little is known about whether disordered cannabis use is associated with an increased risk of a dementia diagnosis.ObjectiveTo investigate the association between emergency department visits or hospitalizations (acute care encounters) due to cannabis and future dementia diagnosis.Design, Setting, and ParticipantsPopulation-based, retrospective, matched cohort study using health administrative data from Ontario, Canada, between 2008 and 2021 (with follow-up until 2022) including all individuals aged 45 to 105 years living in Ontario who were eligible and did not have a diagnosis of dementia at cohort entry (2 620 083 individuals excluded).ExposureIndividuals with incident acute care due to cannabis use, defined using <jats:italic>International Classification of Diseases and Related Health Problems, Tenth Revision</jats:italic> coding.Main Outcomes and MeasuresWe used cause-specific adjusted hazard models to compare new diagnoses of dementia (from a validated algorithm) between individuals with acute care due to cannabis use with (1) individuals with all-cause acute care (excluding cannabis), (2) the general population, and (3) individuals with acute care due to alcohol use.ResultsThe study included 6 086 794 individuals, of whom 16 275 (0.3%) had incident acute care due to cannabis use (mean age, 55.2 [SD, 8.3] years; 60.3% male). Annual rates of incident acute care due to cannabis use increased 5.0-fold in individuals aged 45 to 64 years (from 10.16 to 50.65 per 100 000) and 26.7-fold in individuals aged 65 years or older (from 0.65 to 16.99 per 100 000) between 2008 and 2021. Individuals with incident acute care due to cannabis use were at a 1.5-fold and 3.9-fold increased risk of dementia diagnosis within 5 years relative to individuals with all-cause acute care and the general population of the same age and sex, respectively (absolute rates of dementia diagnosis: 5.0% for cannabis-related acute care, 3.6% for all-cause acute care, and 1.3% in the general population). After adjustment for sociodemographics and chronic health conditions, individuals with acute care due to cannabis use remained at elevated risk relative to those with all-cause acute care (adjusted hazard ratio [aHR], 1.23; 95% CI, 1.09-1.39) and the general population (aHR, 1.72; 95% CI, 1.38-2.15). Individuals with acute care due to cannabis use were at lower risk than those with acute care due to alcohol use (aHR, 0.69; 95% CI, 0.62-0.76).Conclusions and RelevanceIndividuals with cannabis use severe enough to require hospital-based care were at increased risk of a new dementia diagnosis compared with those with all-cause hospital-based care or the general population. These findings have important implications considering increasing cannabis use among older adults.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"60 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827726","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":"Mind the Itch","authors":"David Matuskey","doi":"10.1001/jamaneurol.2025.0479","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0479","url":null,"abstract":"This essay details the author’s personal experience with poison ivy itch and the synchronicity of a similar realization for a patient at his former facility.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"37 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790165","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":"Apraxia of Eyelid Opening in Myasthenia Gravis","authors":"Ryan Naum, Jonathan Morena","doi":"10.1001/jamaneurol.2025.0704","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0704","url":null,"abstract":"This case report describes a 61-year-old man with myasthenia gravis initially diagnosed with blepharospasm who was later found to have the nonparalytic disorder apraxia of eyelid opening.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"10 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790152","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":"GLP-1 Receptor Agonists-From Breakthroughs in Cardiometabolic Treatment to Emerging Neuroprotective Potential.","authors":"Diana Thiara","doi":"10.1001/jamaneurol.2025.0237","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0237","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795606","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":"Cardioprotective Glucose-Lowering Agents and Dementia Risk","authors":"Allie Seminer, Alfredi Mulihano, Clare O’Brien, Finn Krewer, Maria Costello, Conor Judge, Martin O’Donnell, Catriona Reddin","doi":"10.1001/jamaneurol.2025.0360","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0360","url":null,"abstract":"ImportanceAlthough diabetes is a risk factor for dementia, the effect of glucose-lowering therapy for prevention of incident dementia is uncertain.ObjectiveTo determine whether cardioprotective glucose-lowering therapy (sodium-glucose cotransporter-2 inhibitors [SGLT2is], glucagon-like peptide-1 receptor agonists [GLP-1RAs], metformin, and pioglitazone), compared with controls, was associated with a reduction in risk of dementia or cognitive impairment, and among primary dementia subtypes.Data SourcesThe PubMed and Embase databases were searched for studies published from inception of the database to July 11, 2024.Study SelectionRandomized clinical trials comparing cardioprotective glucose-lowering therapy with controls that reported dementia or change in cognitive scores. Cardioprotective glucose-lowering therapies were defined as drug classes recommended by guidelines for reduction of cardiovascular events, based on evidence from phase III randomized clinical trials. Inclusion criteria were assessed independently and inconsistencies were resolved by consensus.Data Extraction and SynthesisData were screened and extracted independently by 2 authors adhering to the PRISMA guidelines in August 2024. Random-effects meta-analysis models were used to estimate a pooled treatment effect.Main Outcomes and MeasuresThe primary outcome measure was dementia or cognitive impairment. The secondary outcomes were primary dementia subtypes, including vascular and Alzheimer dementia, and change in cognitive scores.ResultsTwenty-six randomized clinical trials were eligible for inclusion (N = 164 531 participants), of which 23 trials (n = 160 191 participants) reported the incidence of dementia or cognitive impairment, including 12 trials evaluating SGLT2is, 10 trials evaluating GLP-1RAs, and 1 trial evaluating pioglitazone (no trials of metformin were identified). The mean (SD) age of trial participants was 64.4 (3.5) years and 57 470 (34.9%) were women. Overall, cardioprotective glucose-lowering therapy was not significantly associated with a reduction in cognitive impairment or dementia (odds ratio [OR], 0.83 [95% CI, 0.60-1.14]). Among drug classes, GLP-1RAs were associated with a statistically significant reduction in dementia (OR, 0.55 [95% CI, 0.35-0.86]), but not SGLT2is (OR, 1.20 [95% CI, 0.67-2.17]; <jats:italic>P</jats:italic> value for heterogeneity = .04).Conclusions and RelevanceWhile cardioprotective glucose-lowering therapies were not associated with an overall reduction in all-cause dementia, this meta-analysis of randomized clinical trials found that glucose lowering with GLP-1RAs was associated with a statistically significant reduction in all-cause dementia.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"25 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790169","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}