Cognitive Trajectories from Preclinical Alzheimer's Disease to Dementia
Year: 2026
Type: article
Abstract: Alzheimer's disease (AD) is marked by progressive cognitive decline, highlighting the importance of cognitive assessment in both clinical practice and research. This study investigates the temporal dynamics of cognitive decline and the differential sensitivity of cognitive measures across the AD spectrum. Cognitive measures, functional assessments, and amyloid-beta (Aβ) and tau positron emission tomography (PET) scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) are analyzed using a latent-time disease progression model. Data from 1,447 participants across cognitively normal, mild cognitive impairment, and dementia stages are positioned along an estimated AD timeline. The model estimates a ∼20-year progression from initial Aβ PET positivity to late-stage dementia. Cognitive trajectories reveal that cognitive measures deviate at different time points, with varying levels of abnormality across the disease continuum. These findings demonstrate that cognitive measures differ markedly in their sensitivity across the AD continuum. Characterizing when specific measures become abnormal provides a framework for stage-appropriate test selection in clinical practice, improving clinical interpretation while informing the choice of cognitive endpoints and inclusion criteria in clinical trials.
Source: Advanced Science
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,730
Funders: Gates Ventures, U.S. Department of Defense, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Biogen, University of Southern California, F. Hoffmann-La Roche, Meso Scale Diagnostics, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Novartis Pharmaceuticals Corporation, Northern California Institute for Research and Education, National Institute for Health and Care Research, University College London, European Commission, National Research Foundation of Korea, Eisai, Hjärnfonden, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Göteborgs Universitet, Servier, H. Lundbeck A/S, IXICO, National Institutes of Health, Genentech, HORIZON EUROPE Framework Programme, Canadian Institutes of Health Research, Sahlgrenska Akademin, Wallenberg Centre for Molecular and Translational Medicine, National Institute on Aging
Awards: G1012222616, G1389459409, G1625299662, DS-ARC: A Remote Digital Cognitive Assessment for Down Syndrome-Associated Alzheimer's Disease, Long-term effects of COVID-19 on the central nervous system, G2228122249, G2423387114, G2522063444, G2627015116, G2835601961, G29951154, Synaptic remodelling during human skill learning, G3216574877, Mapping early neuropathological processes associated with the development of dementia using neuroimaging, G3616604534, G3870774570, G3966393351, REAL-WORLD IMPLEMENTATION, DEPLOYMENT AND VALIDATION OF EARLY DETECTION TOOLS AND LIFESTYLE ENHANCEMENT, G6134497586, REAL AD - Validation of a realistic population screening approach for early Alzheimer´s disease, G7273465525, G764699806, PRECISION MEDICINE PLATFORM IN NEURODEGENERATIVE DISEASE, G9000122335
OpenAlex ID: W7143423062