JAMA neurologyPub Date : 2024-11-11DOI: 10.1001/jamaneurol.2024.3831
Andrea O. Rossetti, Sarah Benghanem
{"title":"Epileptiform Electrographic Patterns After Cardiac Arrest","authors":"Andrea O. Rossetti, Sarah Benghanem","doi":"10.1001/jamaneurol.2024.3831","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.3831","url":null,"abstract":"This Viewpoint challenges conventional clinical practice that eschews pharmacological intervention for comatose patients with epileptiform abnormalities after cardiac arrest using evidence from the Treatment of Electroencephalographic Status Epilepticus after Cardiopulmonary Resuscitation (TELSTAR) trial.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"95 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598511","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}
JAMA neurologyPub Date : 2024-11-11DOI: 10.1001/jamaneurol.2024.3774
David D. Ward, Jonny P. Flint, Thomas J. Littlejohns, Isabelle F. Foote, Marco Canevelli, Lindsay M. K. Wallace, Emily H. Gordon, David J. Llewellyn, Janice M. Ranson, Ruth E. Hubbard, Kenneth Rockwood, Erwin Stolz
{"title":"Frailty Trajectories Preceding Dementia in the US and UK","authors":"David D. Ward, Jonny P. Flint, Thomas J. Littlejohns, Isabelle F. Foote, Marco Canevelli, Lindsay M. K. Wallace, Emily H. Gordon, David J. Llewellyn, Janice M. Ranson, Ruth E. Hubbard, Kenneth Rockwood, Erwin Stolz","doi":"10.1001/jamaneurol.2024.3774","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.3774","url":null,"abstract":"ImportanceAn accessible marker of both biological age and dementia risk is crucial to advancing dementia prevention and treatment strategies. Although frailty is a candidate for that role, the nature of the relationship between frailty and dementia is not well understood.ObjectiveTo clarify the temporal relationship between frailty and incident dementia by investigating frailty trajectories in the years preceding dementia onset.Design, Setting, and ParticipantsParticipant data came from 4 prospective cohort studies: the English Longitudinal Study of Ageing, the Health and Retirement Study, the Rush Memory and Aging Project, and the National Alzheimer Coordinating Center. Data were collected between 1997 and 2024 and were analyzed from July 2023 to August 2024. The settings were retirement communities, national-level surveys, and a multiclinic-based cohort. Included individuals were 60 years or older and without cognitive impairment at baseline. Included individuals also had data on age, sex, education level, and ethnicity and a frailty index score calculated at baseline.ExposureFrailty was the main exposure, with participants’ degrees of frailty quantified using retrospectively calculated frailty index scores.Main Outcomes and MeasuresIncident all-cause dementia ascertained through physician-derived diagnoses, self- and informant-report, and estimated classifications based on combinations of cognitive tests.ResultsThe participant number before exclusions was 87 737. After exclusions, data from 29 849 participants (mean [SD] age, 71.6 [7.7] years; 18 369 female [62%]; 257 963 person-years of follow-up; 3154 cases of incident dementia) were analyzed. Bayesian generalized linear mixed regression models revealed accelerations in frailty trajectories 4 to 9 years before incident dementia. Overall, frailty was positively associated with dementia risk (adjusted hazard ratios [aHRs] ranged from 1.18; 95% CI, 1.13-1.24 to 1.73; 95% CI, 1.57-1.92). This association held among participants whose time between frailty measurement and incident dementia exceeded the identified acceleration period (aHRs ranged from 1.18; 95% CI, 1.12-1.23 to 1.43; 95% CI, 1.14-1.80).Conclusions and RelevanceThese findings suggest that frailty measurements may be used to identify high-risk population groups for preferential enrolment into clinical trials for dementia prevention and treatment. Frailty itself may represent a useful upstream target for behavioral and societal approaches to dementia prevention.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"154 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598508","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}
JAMA neurologyPub Date : 2024-11-11DOI: 10.1001/jamaneurol.2024.3825
Nunzio Pomara, Bruno Pietro Imbimbo
{"title":"Gantenerumab in Dominantly Inherited Alzheimer Disease.","authors":"Nunzio Pomara, Bruno Pietro Imbimbo","doi":"10.1001/jamaneurol.2024.3825","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.3825","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620708","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}
JAMA neurologyPub Date : 2024-11-04DOI: 10.1001/jamaneurol.2024.3733
Scott Ayton, David Barton, Bruce Brew, Amy Brodtmann, Roger Clarnette, Patricia Desmond, David Devos, Kathryn A Ellis, Amir Fazlollahi, Caroline Fradette, Anita M Y Goh, Pawel Kalinowski, Christopher Kyndt, Rosalyn Lai, Yen Ying Lim, Paul Maruff, Terence J O'Brien, Christopher Rowe, Olivier Salvado, Peter W Schofield, Michael Spino, Fernando Tricta, Aaron Wagen, Robert Williams, Michael Woodward, Ashley I Bush
{"title":"Deferiprone in Alzheimer Disease: A Randomized Clinical Trial.","authors":"Scott Ayton, David Barton, Bruce Brew, Amy Brodtmann, Roger Clarnette, Patricia Desmond, David Devos, Kathryn A Ellis, Amir Fazlollahi, Caroline Fradette, Anita M Y Goh, Pawel Kalinowski, Christopher Kyndt, Rosalyn Lai, Yen Ying Lim, Paul Maruff, Terence J O'Brien, Christopher Rowe, Olivier Salvado, Peter W Schofield, Michael Spino, Fernando Tricta, Aaron Wagen, Robert Williams, Michael Woodward, Ashley I Bush","doi":"10.1001/jamaneurol.2024.3733","DOIUrl":"10.1001/jamaneurol.2024.3733","url":null,"abstract":"<p><strong>Importance: </strong>Interventions that substantially slow neurodegeneration are needed to address the growing burden of Alzheimer disease (AD) to societies worldwide. Elevated brain iron observed in AD has been associated with accelerated cognitive decline and may be a tractable drug target.</p><p><strong>Objective: </strong>To investigate whether the brain-permeable iron chelator deferiprone slows cognitive decline in people with AD.</p><p><strong>Design, setting, and participants: </strong>This phase 2, double-masked, placebo-controlled randomized clinical trial of 12-month duration was conducted at 9 sites in Australia between August 2, 2018, and April 1, 2023. Patients older than 54 years with amyloid-confirmed mild cognitive impairment or early AD (a Mini-Mental State Examination score of 20 or higher) were screened. Randomization was 2:1 and masked to participants and all study staff.</p><p><strong>Interventions: </strong>Deferiprone 15 mg/kg twice a day or placebo administered orally for 12 months.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was a composite cognitive measure assessed at baseline, 6 months, and 12 months using a neuropsychological test battery (NTB) of memory, executive function, and attention tasks. Secondary outcomes included change in brain iron burden measured by quantitative susceptibility mapping (QSM) magnetic resonance imaging (target engagement), brain volume changes (secondary efficacy measure), and adverse events (safety analysis).</p><p><strong>Results: </strong>Of 167 patients screened for eligibility, 81 were included, with 53 randomly assigned to the deferiprone group (mean [SD] age, 73.0 [8.0] years; 29 male [54.7%]) and 28 to the placebo group (mean [SD] age, 71.6 [7.2] years; 17 male [60.7%]); 54 participants completed the study (7 [25.0%] withdrew from the placebo group and 20 [37.7%] from the deferiprone group). In an intention-to-treat analysis, participants in the deferiprone group showed accelerated cognitive decline on the NTB primary outcome (β for interaction = -0.50; 95% CI, -0.80 to -0.20) compared with placebo (change in NTB composite z score for deferiprone, -0.80 [95% CI, -0.98 to -0.62]; for placebo, -0.30 [95% CI, -0.54 to -0.06]). Secondary analysis revealed that this result was driven by worsening performance on executive function tests. The QSM confirmed that deferiprone decreased iron in the hippocampus compared with placebo (change in hippocampal QSM for deferiprone, -0.36 ppb [95% CI, -0.76 to 0.04 ppb]; for placebo, 0.32 ppb [95% CI, -0.12 to 0.75 ppb]; β for interaction = -0.68 [95% CI, -1.27 to -0.09]). Longitudinal hippocampal volume loss was not affected by deferiprone, but exploratory analysis of other brain regions revealed increased volume loss with deferiprone in frontal areas. The frequency of the adverse effect of neutropenia (4 participants [7.5%] in the deferiprone group) was higher than in similar studies (1.6%-4.4%).</p><p><strong>C","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568645","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}
JAMA neurologyPub Date : 2024-10-28DOI: 10.1001/jamaneurol.2024.3619
Christopher D Smyser, Donna M Ferriero, Laura R Ment
{"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":"https://doi.org/10.1001/jamaneurol.2024.3619","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2024-10-28","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}
JAMA neurologyPub Date : 2024-10-21DOI: 10.1001/jamaneurol.2024.3568
Lee E. Neilson, Kelly M. Reavis, Jack Wiedrick, Gregory D. Scott
{"title":"Hearing Loss, Incident Parkinson Disease, and Treatment With Hearing Aids","authors":"Lee E. Neilson, Kelly M. Reavis, Jack Wiedrick, Gregory D. Scott","doi":"10.1001/jamaneurol.2024.3568","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.3568","url":null,"abstract":"ImportanceThe risk of developing Parkinson disease (PD) after objective hearing loss is unknown. PD studies using self-reported hearing loss are insensitive, and objective data are lacking.ObjectiveTo examine the association of hearing loss with incident PD in US veterans and its effect modification by well-established prodromal conditions and hearing aids.Design, Setting, and ParticipantsThis cohort study analyzed electronic health record data from the US Department of Veterans Affairs for veterans who had an audiogram from January 1, 1999, to December 30, 2022. Individuals with data missing or a preexisting PD diagnosis were excluded.ExposureAudiogram-confirmed hearing loss.Main Outcomes and MeasuresCumulative incidence of PD was calculated with adjustment for competing risk of death.ResultsAmong 7 296 051 veterans with an audiogram, 3 596 365 were included. They were mostly male (n = 3 452 898 [96%]) and had a mean (SD) age of 67 (10.3) years. A total of 750 010 individuals (20.8%) had normal hearing at the time of audiometry examination; among those with hearing loss, 1 080 651 (30.0%), 1 039 785 (28.9%), 568 296 (15.8%), and 157 623 (4.3%) individuals had mild (20-&amp;lt;35 dB), moderate (35-&amp;lt;50 dB), moderate to severe (50-&amp;lt;65 dB), and severe to profound (65-120 dB) hearing loss, respectively. Age, gender, and smoking history were balanced between all exposed and unexposed groups with further adjustment for race, ethnicity, and frailty. At 10 years after the baseline audiogram, the numbers of additional cases of PD were 6.1 (95% CI, 4.5-7.79, 15.8 (95% CI, 12.8-18.8), 16.2 (95% CI, 11.9-20.6), and 12.1 (95% CI, 4.5-19.6) among veterans with mild, moderate, moderate to severe, and severe to profound hearing loss, respectively, compared with those with normal hearing. When combined with established prodromal conditions, hearing loss was associated with 5.7 (95% CI, 2.2-9.2) additional cases of PD at 10 years compared with either condition alone. With prompt hearing aid dispensation, incident cases of PD decreased by 21.6 cases (95% CI, 19.5-23.6) at 10 years.Conclusions and RelevanceHearing loss appears to be an independent risk factor for later development of PD. Hearing aids attenuate this risk, and therefore widespread screening for hearing loss and appropriate use of hearing aids may reduce the incidence of PD. Additional studies are needed to examine the mechanisms underlying the association between hearing loss and PD.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"116 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452139","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}