JAMA neurology最新文献

{"title":"Londonderry Air.","authors":"Calvin G Ludwig","doi":"10.1001/jamaneurol.2024.4481","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.4481","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931794","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":"An Acetylcholine M1 Receptor-Positive Allosteric Modulator (TAK-071) in Parkinson Disease With Cognitive Impairment: A Phase 2 Randomized Clinical Trial.","authors":"Niraj M Shanbhag, Jaya L Padmanabhan, Zheng Zhang, Brian T Harel, Hongxia Jia, Tairmae Kangarloo, Wei Yin, Ariel V Dowling, Antonio Laurenza, Polyna Khudyakov, Kevin Galinsky, Robert D Latzman, Tanya Simuni, Daniel Weintraub, Fay B Horak, Cindy Lustig, Paul Maruff, Arthur A Simen","doi":"10.1001/jamaneurol.2024.4519","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.4519","url":null,"abstract":"<p><strong>Importance: </strong>Fall risk and cognitive impairment are prevalent and burdensome in Parkinson disease (PD), requiring efficacious, well-tolerated treatment.</p><p><strong>Objective: </strong>To evaluate the safety and efficacy of TAK-071, a muscarinic acetylcholine M1 positive allosteric modulator, in participants with PD, increased fall risk, and cognitive impairment.</p><p><strong>Design, setting, and participants: </strong>This phase 2 randomized double-blind placebo-controlled crossover clinical trial was conducted from October 21, 2020, to February 27, 2023, at 19 sites in the US. Participants included patients aged 40 to 85 years with a diagnosis of PD, with at least 1 fall in the prior 12 months, with a Montreal Cognitive Assessment score of 11 to 26, and receiving stable antiparkinsonian medications and no acetylcholinesterase inhibitors.</p><p><strong>Intervention: </strong>One-to-one randomization to once-daily oral TAK-071 or placebo for 6 weeks, followed by washout and 6 weeks of crossover treatment.</p><p><strong>Main outcomes and measures: </strong>The primary end point was change from baseline in gait variability (stride time variability [STV]) during a 2-minute walk test with or without cognitive load. The secondary efficacy end point was change from baseline in a cognitive composite score consisting of tests of attention, executive function, and memory.</p><p><strong>Results: </strong>Among the 54 participants included in the analysis, 45 (83%) were male, mean (SD) age was 69.7 (6.9) years, and median Montreal Cognitive Assessment score was 24 (range, 17-26). After 6 weeks of treatment, the primary outcome was negative: the change from baseline in STV did not differ between participants receiving TAK-071 or placebo, with cognitive load (geometric mean ratio, 1.15; 95% CI, 0.94-1.41; P = .16) or without cognitive load (geometric mean ratio, 1.02; 95% CI, 0.88-1.18; P = .78). TAK-071 improved the secondary efficacy outcome (cognitive composite score) vs placebo. The least squares mean difference of the change from baseline was 0.22 (95% CI, 0.05-0.38; P = .01). Treatment-emergent adverse events occurred in 18 of 49 participants (37%) while receiving placebo and in 19 of 53 (36%) while receiving TAK-071. Four participants (8%) receiving TAK-071 had adverse events resulting in withdrawal of study drug; 4 had gastrointestinal tract adverse events.</p><p><strong>Conclusions and relevance: </strong>In this study, in participants with PD, risk for falls, and cognitive impairment, TAK-071 was well-tolerated. The treatment did not improve the primary outcome of gait variability, but did improve cognition compared with placebo. Larger and longer studies in more diverse populations are needed to better understand the safety and efficacy of TAK-071 in broader populations.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04334317.</p>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931698","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":"Intracranial Metastatic Tumor Hemorrhage During MRI Scanning.","authors":"Wei Rao, Jin-Long Mao, Wei-Dong Cao","doi":"10.1001/jamaneurol.2024.4531","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.4531","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931789","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":"Cardiovascular Safety of Anti-CGRP Monoclonal Antibodies in Older Adults or Adults With Disability With Migraine.","authors":"Seonkyeong Yang, Yulia Orlova, Haesuk Park, Steven M Smith, Yi Guo, Benjamin A Chapin, Debbie L Wilson, Wei-Hsuan Lo-Ciganic","doi":"10.1001/jamaneurol.2024.4537","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.4537","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP mAbs) offer effective migraine-specific preventive treatment. However, concerns exist about their potential cardiovascular risks due to CGRP blockade.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To compare the incidence of cardiovascular disease (CVD) between Medicare beneficiaries with migraine who initiated anti-CGRP-mAbs vs onabotulinumtoxinA in the US.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;This retrospective, sequential cohort study was conducted among a nationally representative population-based sample of Medicare claims from May 2018 through December 2020. Data analysis was performed from August to December 2023. This study included fee-for-service Medicare beneficiaries aged 18 years or older with migraine who initiated either anti-CGRP mAbs or onabotulinumtoxinA. Beneficiaries who had a history of myocardial infarction (MI), stroke, cluster headache, malignant cancer, or hospice service within a 1-year baseline period prior to treatment initiation were excluded. To minimize channeling bias from new drug introductions and time-related bias due to the COVID-19 pandemic, 5 cohorts were established, representing sequential 6-month calendar intervals based on the initial prescription or date of index anti-CGRP mAbs or onabotulinumtoxinA use.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposure: &lt;/strong&gt;Anti-CGRP mAbs vs onabotulinumtoxinA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;The primary outcome was time to first MI or stroke. Secondary outcomes included hypertensive crisis, peripheral revascularization, and Raynaud phenomenon. The inverse probability of treatment-weighted Cox proportional hazards models were used to compare outcomes between the 2 treatment groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 266 848 eligible patients with migraine, 5153 patients initiated anti-CGRP mAbs (mean [SD] age, 57.8 [14.0] years; 4308 female patients [83.6%]) and 4000 patients initiated onabotulinumtoxinA (mean [SD] age, 61.9 [13.7] years; 3353 female patients [83.8%]). Use of anti-CGRP mAbs was not associated with an increased risk of composite CVD events (adjusted hazard ratio [aHR], 0.88; 95% CI, 0.44-1.77), hypertensive crisis (aHR, 0.46; 95% CI, 0.14-1.55), peripheral revascularization (aHR, 1.50; 95% CI, 0.48-4.73), or Raynaud phenomenon (aHR, 0.75; 95% CI, 0.45-1.24) compared with onabotulinumtoxinA. Subgroup analyses by age group and presence of established non-MI or stroke CVD showed similar findings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;In this cohort study, despite initial concerns regarding the cardiovascular effects of CGRP blockade, anti-CGRP mAbs were not associated with an increased risk of CVD compared with onabotulinumtoxinA among adult Medicare beneficiaries with migraine, who were predominantly older adults or individuals with disability. Future studies with longer follow-up periods and in other ","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931710","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":"Immediate or Delayed Statin in Acute Atherosclerotic Ischemia.","authors":"Anastasios Kollias, Konstantinos G Kyriakoulis, Kyriakos Dimitriadis","doi":"10.1001/jamaneurol.2024.3747","DOIUrl":"10.1001/jamaneurol.2024.3747","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"110"},"PeriodicalIF":20.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568648","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":"Neuropsychological Outcomes in 6-Year-Old Children of Women With Epilepsy: A Prospective Nonrandomized Clinical Trial.","authors":"Kimford J Meador, Morris J Cohen, David W Loring, Abigail G Matthews, Carrie Brown, Chelsea P Robalino, Andrea Carmack, Angela K Birnbaum, Paula E Voinescu, Elizabeth E Gerard, Laura A Kalayjian, Evan R Gedzelman, Julie Hanna, Jennifer Cavitt, Maria Sam, Sean Hwang, Alison M Pack, Jacqueline A French, Jeffrey J Tsai, Cora Taylor, Page B Pennell","doi":"10.1001/jamaneurol.2024.3982","DOIUrl":"10.1001/jamaneurol.2024.3982","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Antiseizure medications (ASMs) are potential teratogens commonly prescribed for multiple indications. ASM fetal exposure can impair neurodevelopment. Folate improves pregnancy outcomes, but higher doses may pose risks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To compare the outcomes of 6-year-old children of women with epilepsy (WWE) vs those of healthy women (HW), and assess the association of outcomes to third-trimester ASM exposures.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;After informed consent, pregnant WWE and HW were enrolled from 2012 through 2016 in this prospective, multicenter, nonrandomized clinical trial. Children were assessed at 6 years of age (2019-2022). Participants were recruited from 20 US epilepsy centers. Study data were analyzed from August 2023 to August 2024.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposures: &lt;/strong&gt;Fetal ASM exposures.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;The a priori main neurodevelopmental outcome was the blindly assessed Verbal Index Score in 6-year-old children. The Verbal Index Score is calculated as the mean of the scores from the Word Definitions and Verbal Similarities subtests from the Differential Ability Scales, Expressive One-Word Picture Vocabulary Test, Phonological Processing, Comprehension of Instructions, and Sentence Repetition subtests from the Neuropsychological Assessment and Peabody Picture Vocabulary Test. The 2 primary analyses (1) compared children of WWE and HW using linear regression and (2) examined the outcomes of fetal exposure via ASM blood concentrations. Analyses were adjusted for multiple potential confounding factors. Other outcomes and folate exposure-related outcomes were assessed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 1123 pregnant women were screened, and 456 were enrolled (426 did not meet criteria, and 241 chose not to participate). A total of 298 children of WWE (mean [SD] age, 6.4 [4.2] years; 158 female [53.0%]; 140 male [47.0%]) vs 89 children of HW (mean [SD] age, 6.4 [4.2] years; 41 female [46.1%]; 48 male [53.9%]) did not differ on Verbal Index Score (parameter estimate, -0.6; 95% CI, -3.2 to 1.9; P = .64). Exposure-dependent outcomes differed across ASMs. Assessment of other ASMs was limited because 232 of 298 WWE (78%) were taking lamotrigine or levetiracetam alone or in combination. Folate supplementation during the first 12 weeks of pregnancy had positive associations with cognition and behavior with no signal for risks at higher folate doses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;Results of this prospective nonrandomized clinical trial suggest that verbal abilities in children of WWE vs HW did not differ. Exposure-dependent outcomes of ASMs highlight the importance of dosing high enough to protect the mother and fetus from seizures but low enough to protect the fetus. Folate supplementation early in pregnancy including higher doses was associated with improved cognitive and behavioral outcomes. Additio","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"30-39"},"PeriodicalIF":20.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709466","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":"Disease Severity Staging System for NOTCH3-Associated Small Vessel Disease, Including CADASIL.","authors":"Gido Gravesteijn, Julie W Rutten, Minne N Cerfontaine, Remco J Hack, Yi-Chu Liao, Amy A Jolly, Stéphanie Guey, Shao-Lun Hsu, Jae-Young Park, Yun Yuan, Anna Kopczak, Nicola Rifino, Sam J Neilson, Anna Poggesi, Md Manjurul Islam Shourav, Satoshi Saito, Hiroyuki Ishiyama, Ana Domínguez Mayoral, Renata Nogueira, Elena Muiño, Pia Andersen, Nicola De Stefano, Gustavo Santo, Nontapat Sukhonpanich, Francesco Mele, Ashley Park, Jung Seok Lee, Mar Rodríguez-Girondo, Sebastiaan J J Vonk, Amy Brodtmann, Anne Börjesson-Hanson, Leonardo Pantoni, Israel Fernández-Cadenas, Ana Rita Silva, Vinícus V A Montanaro, Rajesh N Kalaria, Diego Lopergolo, Masafumi Ihara, James F Meschia, Keith W Muir, Anna Bersano, Francesca Pescini, Marco Duering, Jay Chol Choi, Chen Ling, Hyunjin Kim, Hugh S Markus, Hugues Chabriat, Yi-Chung Lee, Saskia A J Lesnik Oberstein","doi":"10.1001/jamaneurol.2024.4487","DOIUrl":"10.1001/jamaneurol.2024.4487","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Typical cysteine-altering NOTCH3 (NOTCH3cys) variants are highly prevalent (approximately 1 in 300 individuals) and are associated with a broad spectrum of small vessel disease (SVD), ranging from early-onset stroke and dementia (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]) to nonpenetrance. A staging system that captures the full NOTCH3-SVD severity spectrum is needed and currently lacking.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To design a simple disease severity staging system that captures the broad clinicoradiological NOTCH3-SVD severity spectrum.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;A cohort study was performed in which the NOTCH3-SVD severity staging system was developed using a discovery cohort (2019-2020) and validated in independent international CADASIL cohorts (1999-2023) and the UK Biobank. Clinical and imaging data were collected from participants originating from 23 international CADASIL cohorts and from the UK Biobank. Eligibility criteria were presence of a NOTCH3cys variant, availability of brain magnetic resonance imaging, and modified Rankin Scale score. The discovery cohort consisted of 195 NOTCH3cys-positive cases from families with CADASIL; the validation set included 1713 NOTCH3cys-positive cases from 15 countries. The UK Biobank cohort consisted of 101 NOTCH3cys-positive individuals. Data from 2-year (2019-2023) and 18-year (1999-2017) follow-up studies were also analyzed. Data analysis was performed from July 2023 to August 2024.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;Percentage of cases following the sequence of events of the NOTCH3-SVD stages, and the association between the stages and ischemic stroke, intracerebral hemorrhage, global cognition, processing speed, brain volume, brain microstructural damage, and serum neurofilament light chain (NfL) level.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The NOTCH3-SVD staging system encompasses 9 disease stages or substages, ranging from stage 0 (premanifest stage) to stage 4B (end stage). Of all 1908 cases, which included 195 in the discovery cohort (mean [SD] age, 52.4 [12.2] years) and 1713 in the validation cohorts (mean [SD] age, 53.1 [13.0] years), 1789 (94%) followed the sequence of events defined by the NOTCH3-SVD staging system. The NOTCH3-SVD stages were associated with neuroimaging outcomes in the NOTCH3cys-positive cases in the CADASIL cohorts and in the UK Biobank and with cognitive outcomes and serum NfL level in cases from the CADASIL cohorts. The NOTCH3-SVD staging system captured disease progression and was associated with 18-year survival.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;The NOTCH3-SVD staging system captures the full disease spectrum, from asymptomatic individuals with a NOTCH3cys variant to patients with end-stage disease. The NOTCH3-SVD staging system is a simple but effective tool for uniform disease staging in the clinic and in res","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"49-60"},"PeriodicalIF":20.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750882","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":"Trends in Gender, Racial, and Ethnic Representation Among US Neurology Faculty.","authors":"Chia-Chen Tsai, Chen Hu, Jeffrey Ding, Esther Bui, Aleksandra Pikula, Thalia S Field, Sabeen Tiwana, Javed Siddiqi, Faisal Khosa","doi":"10.1001/jamaneurol.2024.3909","DOIUrl":"10.1001/jamaneurol.2024.3909","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"106-108"},"PeriodicalIF":20.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647948","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":"Amyloid-Related Imaging Abnormalities (ARIA) in Clinical Trials of Gantenerumab in Early Alzheimer Disease.","authors":"Stephen Salloway, Jakub Wojtowicz, Nicola Voyle, Christopher A Lane, Gregory Klein, Marco Lyons, Simona Rossomanno, Francesca Mazzo, Szofia Bullain, Frederik Barkhof, Tobias Bittner, Andres Schneider, Michael Grundman, Roxana Aldea, Mercè Boada, Janice Smith, Rachelle Doody","doi":"10.1001/jamaneurol.2024.3937","DOIUrl":"10.1001/jamaneurol.2024.3937","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Data from 2 phase 3 studies of gantenerumab, GRADUATE I/II, and their open-label extensions represent a resource to further characterize amyloid-related imaging abnormalities (ARIA), including long-term sequelae.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To describe the characteristics of ARIA and risk factors and clinical consequences of ARIA-edema (ARIA-E).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;Secondary data collection from the GRADUATE I/II phase 3 randomized, double-blind, placebo-controlled, 116-week parallel-group studies and their open-label extensions, including PostGraduate, with up to 210 (mean, 125) weeks of total gantenerumab treatment were conducted between 2018 and 2023. The study included multicenter trials at 288 sites across 30 countries. GRADUATE I/II enrolled 985 and 980 participants, respectively, with early symptomatic Alzheimer disease (AD) and amyloid-beta (Aβ) pathology who were aged 50 to 90 years. PostGraduate enrolled 1382 participants (671 previously randomized to gantenerumab). Data were analyzed from November 2, 2022, to October 10, 2023.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interventions: &lt;/strong&gt;GRADUATE I/II participants were randomized 1:1 to gantenerumab or placebo. Nine-month uptitration was used to mitigate ARIA risk.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;Postbaseline safety monitoring, including brain magnetic resonance imaging (MRI) findings, and adverse events and cognitive assessments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The safety-evaluable MRI population of GRADUATE I/II comprised 1939 participants (mean age, 71.7 years; 1105 female [57.0%]). Severity of AD-related Aβ neuropathology (lower cerebrospinal fluid [CSF] Aβ42, hazard ratio [HR] for CSF Aβ42: 0.4; 95% CI, 0.2-0.7) and comorbid cerebrovascular pathology (Fazekas score: HR, 1.6; 95% CI, 1.3-2.0; total superficial siderosis count: HR, 1.9; 95% CI, 1.3-2.6; total microhemorrhage count: HR, 1.3; 95% CI, 1.0-1.5) may be important baseline risk factors for ARIA-E, in addition to apolipoprotein E (APOE) ε4 status (APOE ε4 heterozygous carrier: HR, 2.0; 95% CI, 1.4-2.8 and APOE ε4 homozygous carrier: HR, 4.7; 95% CI, 3.2-6.7). At the group level, ARIA-E did not impact long-term cognitive and functional performance (relative difference in adjusted means for Clinical Dementia Rating-Sum of Boxes was -9% in pooled GRADUATE analysis at week 116 and when censored at first ARIA-E). While taking gantenerumab, ARIA-E and ARIA-hemosiderin occurred in 24.9% (247 of 993) and 22.9% (227 of 993) participants, respectively; first ARIA-E occurred by week 64 in 86.2% (213 of 247) of participants with ARIA-E. Narratives are provided for all serious symptomatic ARIA-E cases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;These results show that in addition to APOE ε4 allele count, severity of Aβ neuropathology and comorbid cerebrovascular pathology may be relevant for clinicians prescribing anti-Aβ monoclonal antibodies for early AD an","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"19-29"},"PeriodicalIF":20.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647940","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":"Neonatal Neurocritical Care Training-The Time Has Come.","authors":"Christopher D Smyser, Donna M Ferriero, Laura R Ment","doi":"10.1001/jamaneurol.2024.3619","DOIUrl":"10.1001/jamaneurol.2024.3619","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"7-8"},"PeriodicalIF":20.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500624","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}