Pub Date : 2026-01-01DOI: 10.1001/jamaneurol.2025.4439
Fawad A Khan, Rubina H Khan
{"title":"\"The Triage of Privilege\" Factual Concerns-Reply.","authors":"Fawad A Khan, Rubina H Khan","doi":"10.1001/jamaneurol.2025.4439","DOIUrl":"10.1001/jamaneurol.2025.4439","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"89-90"},"PeriodicalIF":21.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-29DOI: 10.1001/jamaneurol.2025.5068
Afsaneh Shirani,Olaf Stuve
{"title":"Beyond the Single-Disease Paradigm-Why Distinctions in Multiple Sclerosis Still Matter.","authors":"Afsaneh Shirani,Olaf Stuve","doi":"10.1001/jamaneurol.2025.5068","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5068","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"127 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847256","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":"Wind Swirl Pattern on Density Spectral Array in Anti-GABAB Receptor Encephalitis With Amnestic Seizures.","authors":"Shuichiro Neshige,Naoki Takahashi,Hirofumi Maruyama","doi":"10.1001/jamaneurol.2025.5060","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5060","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"11 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-22DOI: 10.1001/jamaneurol.2025.5065
Julian C Motzkin,Bin He,Kalpna Gupta,Prasad Shirvalkar
{"title":"Chronic Pain Is a Brain Network Disorder.","authors":"Julian C Motzkin,Bin He,Kalpna Gupta,Prasad Shirvalkar","doi":"10.1001/jamaneurol.2025.5065","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.5065","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"183 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-22DOI: 10.1001/jamaneurol.2025.4927
Lauren Elman,James Wymer,Catherine Lomen-Hoerth
{"title":"Tofersen, SOD1, and the Treatability of Amyotrophic Lateral Sclerosis.","authors":"Lauren Elman,James Wymer,Catherine Lomen-Hoerth","doi":"10.1001/jamaneurol.2025.4927","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4927","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"38 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1001/jamaneurol.2025.4966
Ronald C Petersen,Henrik Zetterberg
{"title":"A Test of the Alzheimer Disease Framework-Did It Pass?","authors":"Ronald C Petersen,Henrik Zetterberg","doi":"10.1001/jamaneurol.2025.4966","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4966","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"9 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1001/jamaneurol.2025.4974
Christopher A Brown,Nidhi S Mundada,Katheryn A Q Cousins,Niyousha Sadeghpour,Xueying Lyu,Emily McGrew,Magdalena Korecka,Alice Chen-Plotkin,Long Xie,Laura E M Wisse,John A Detre,Corey T McMillan,Edward B Lee,Ilya M Nasrallah,Sandhitsu R Das,Dawn Mechanic-Hamilton,Paul A Yushkevich,Leslie M Shaw,David A Wolk,
ImportanceEven within individuals who are amyloid positive, clinical symptoms can be impacted by Alzheimer pathology, other pathologic proteins, and cognitive reserve or resilience. Understanding how each of these factors contributes to a patient's clinical presentation is crucial for prognosis and treatment decisions in the era of disease-modifying therapies.ObjectiveTo evaluate tau-clinical mismatch as a means to identify those more likely to harbor copathology and/or exhibit resilience to Alzheimer pathology.Design, Setting, and ParticipantsThis was a longitudinal, observational cohort study conducted from 2004 to 2024. The setting included multiple academic medical centers in the US participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI) or Penn Alzheimer's Disease Research Center (Penn-ADRC). Included in the analysis were individuals with clinical assessment and measures of either tau positron emission tomography (tau-PET) or phosphorylated tau 217 (p-tau217) who were selected from individuals positive for amyloid β (Aβ+) in the ADNI cohort (aged 55-95 years) and the Penn-ADRC cohort (aged 54-92 years).ExposuresClinical assessment (Clinical Dementia Rating Sum of Boxes [CDR-SB]) and tau burden (tau-PET or p-tau217) for mismatch group classification.Main Outcomes and MeasuresCross-sectional measures of neurodegeneration (medial temporal lobe volume and thickness, cortical thickness, TAR DNA-binding protein 43 [TDP-43] imaging signature), α-synuclein cerebrospinal fluid seed-amplification assay, and longitudinal CDR-SB.ResultsA total of 365 participants (mean [SD] age, 75.4 [7.9] years; 192 female [52.6%]) in the ADNI tau-PET group and 524 participants (mean [SD] age, 77.1 [7.9] years; 268 male [51.1%]) in the ADNI p-tau217 group were selected from the 998 individuals who were Aβ+ in the ADNI cohort and used to generate tau-clinical mismatch models with 55.6% to 57.1% classified as canonical (CDR-SB commensurate to tau), 23.7% to 24.7% as resilient (CDR-SB < tau), and 19.3% to 19.7% as vulnerable (CDR-SB > tau). Vulnerable groups had evidence of greater likelihood of copathology, with TDP-43 neurodegeneration patterns and α-synuclein positivity. Mismatch groups showed diverging clinical trajectories with earlier cognitive impairment in vulnerable groups and later impairment in resilient individuals. Similar findings were seen when applied to an independent dataset of 244 individuals (mean [SD] age, 73.7 [6.8] years; 139 female [57.0%]) of the 248 who were Aβ+ in Penn-ADRC cohort. Finally, these models were applied to a cohort receiving antiamyloid therapy to show the utility of this method for predicting individual cognitive trajectories during therapy.Conclusion and RelevanceResults of this cohort study suggest that tau-clinical mismatch identified individuals more likely to have an accelerated disease course due to the presence of copathology and those exhibiting greater cognitive resilience to disease pathology. These models
{"title":"Evaluation of Copathology and Clinical Trajectories in Individuals With Tau-Clinical Mismatch.","authors":"Christopher A Brown,Nidhi S Mundada,Katheryn A Q Cousins,Niyousha Sadeghpour,Xueying Lyu,Emily McGrew,Magdalena Korecka,Alice Chen-Plotkin,Long Xie,Laura E M Wisse,John A Detre,Corey T McMillan,Edward B Lee,Ilya M Nasrallah,Sandhitsu R Das,Dawn Mechanic-Hamilton,Paul A Yushkevich,Leslie M Shaw,David A Wolk, ","doi":"10.1001/jamaneurol.2025.4974","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4974","url":null,"abstract":"ImportanceEven within individuals who are amyloid positive, clinical symptoms can be impacted by Alzheimer pathology, other pathologic proteins, and cognitive reserve or resilience. Understanding how each of these factors contributes to a patient's clinical presentation is crucial for prognosis and treatment decisions in the era of disease-modifying therapies.ObjectiveTo evaluate tau-clinical mismatch as a means to identify those more likely to harbor copathology and/or exhibit resilience to Alzheimer pathology.Design, Setting, and ParticipantsThis was a longitudinal, observational cohort study conducted from 2004 to 2024. The setting included multiple academic medical centers in the US participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI) or Penn Alzheimer's Disease Research Center (Penn-ADRC). Included in the analysis were individuals with clinical assessment and measures of either tau positron emission tomography (tau-PET) or phosphorylated tau 217 (p-tau217) who were selected from individuals positive for amyloid β (Aβ+) in the ADNI cohort (aged 55-95 years) and the Penn-ADRC cohort (aged 54-92 years).ExposuresClinical assessment (Clinical Dementia Rating Sum of Boxes [CDR-SB]) and tau burden (tau-PET or p-tau217) for mismatch group classification.Main Outcomes and MeasuresCross-sectional measures of neurodegeneration (medial temporal lobe volume and thickness, cortical thickness, TAR DNA-binding protein 43 [TDP-43] imaging signature), α-synuclein cerebrospinal fluid seed-amplification assay, and longitudinal CDR-SB.ResultsA total of 365 participants (mean [SD] age, 75.4 [7.9] years; 192 female [52.6%]) in the ADNI tau-PET group and 524 participants (mean [SD] age, 77.1 [7.9] years; 268 male [51.1%]) in the ADNI p-tau217 group were selected from the 998 individuals who were Aβ+ in the ADNI cohort and used to generate tau-clinical mismatch models with 55.6% to 57.1% classified as canonical (CDR-SB commensurate to tau), 23.7% to 24.7% as resilient (CDR-SB < tau), and 19.3% to 19.7% as vulnerable (CDR-SB > tau). Vulnerable groups had evidence of greater likelihood of copathology, with TDP-43 neurodegeneration patterns and α-synuclein positivity. Mismatch groups showed diverging clinical trajectories with earlier cognitive impairment in vulnerable groups and later impairment in resilient individuals. Similar findings were seen when applied to an independent dataset of 244 individuals (mean [SD] age, 73.7 [6.8] years; 139 female [57.0%]) of the 248 who were Aβ+ in Penn-ADRC cohort. Finally, these models were applied to a cohort receiving antiamyloid therapy to show the utility of this method for predicting individual cognitive trajectories during therapy.Conclusion and RelevanceResults of this cohort study suggest that tau-clinical mismatch identified individuals more likely to have an accelerated disease course due to the presence of copathology and those exhibiting greater cognitive resilience to disease pathology. These models","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"42 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752563","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}
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