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Title: Association of Elevated Amyloid and Tau Positron Emission Tomography Signal With Near-Term Development of Alzheimer Disease Symptoms in Older Adults Without Cognitive Impairment.
Austin Authors: Strikwerda-Brown, Cherie;Hobbs, Diana A;Gonneaud, Julie;St-Onge, Frédéric;Binette, Alexa Pichet;Ozlen, Hazal;Provost, Karine;Soucy, Jean-Paul;Buckley, Rachel F;Benzinger, Tammie L S;Morris, John C;Villemagne, Victor L ;Doré, Vincent ;Sperling, Reisa A;Johnson, Keith A;Rowe, Christopher C ;Gordon, Brian A;Poirier, Judes;Breitner, John C S;Villeneuve, Sylvia
Affiliation: Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Quebec, Canada..
Department of Neurology, Massachusetts General Hospital, Boston.. Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, Massachusetts.. Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia
Molecular Imaging and Therapy
Washington University School of Medicine, St Louis, Missouri..
Inserm, Inserm UMR-S U1237, Université de Caen-Normandie, GIP Cyceron, Caen, France..
Douglas Mental Health University Institute, Montreal, Quebec, Canada..
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden..
Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, Massachusetts..
Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada..
McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Quebec, Canada..
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania..
Department of Neurology, Massachusetts General Hospital, Boston..
Issue Date: 30-Jul-2022
Date: 2022
Publication information: JAMA Neurology 2022; 79(10): 975-985
Abstract: National Institute on Aging-Alzheimer's Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer disease (AD). To assess the clinical value of these biological criteria to identify older individuals without cognitive impairment who are at near-term risk of developing symptomatic AD. This longitudinal cohort study used data from 4 independent population-based cohorts (PREVENT-AD, HABS, AIBL, and Knight ADRC) collected between 2003 and 2021. Participants were older adults without cognitive impairment with 1 year or more of clinical observation after amyloid β and tau positron emission tomography (PET). Median clinical follow-up after PET ranged from 1.94 to 3.66 years. Based on binary assessment of global amyloid burden (A) and a composite temporal region of tau PET uptake (T), participants were stratified into 4 groups (A+T+, A+T-, A-T+, A-T-). Presence (+) or absence (-) of neurodegeneration (N) was assessed using temporal cortical thickness. Each cohort was analyzed separately. Primary outcome was clinical progression to mild cognitive impairment (MCI), identified by a Clinical Dementia Rating score of 0.5 or greater in Knight ADRC and by consensus committee review in the other cohorts. Clinical raters were blind to imaging, genetic, and fluid biomarker data. A secondary outcome was cognitive decline, based on a slope greater than 1.5 SD below the mean of an independent subsample of individuals without cognitive impairment. Outcomes were compared across the biomarker groups. Among 580 participants (PREVENT-AD, 128; HABS, 153; AIBL, 48; Knight ADRC, 251), mean (SD) age ranged from 67 (5) to 76 (6) years across cohorts, with between 55% (137/251) and 74% (95/128) female participants. Across cohorts, 33% to 83% of A+T+ participants progressed to MCI during follow-up (mean progression time, 2-2.72 years), compared with less than 20% of participants in other biomarker groups. Progression further increased to 43% to 100% when restricted to A+T+(N+) individuals. Cox proportional hazard ratios for progression to MCI in the A+T+ group vs other biomarker groups were all 5 or greater. Many A+T+ nonprogressors also showed longitudinal cognitive decline, while cognitive trajectories in other groups remained predominantly stable. The clinical prognostic value of NIA-AA research criteria was confirmed in 4 independent cohorts, with most A+T+(N+) older individuals without cognitive impairment developing AD symptoms within 2 to 3 years.
DOI: 10.1001/jamaneurol.2022.2379
ORCID: 0000-0002-5832-9875
Journal: JAMA Neurology
PubMed URL: 35907254
PubMed URL:
Type: Journal Article
Appears in Collections:Journal articles

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