Accelerated functional brain aging in pre-clinical familial Alzheimer's disease.

TitleAccelerated functional brain aging in pre-clinical familial Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2021
AuthorsGonneaud J, Baria AT, Binette APichet, Gordon BA, Chhatwal JP, Cruchaga C, Jucker M, Levin J, Salloway S, Farlow M, Gauthier S, Benzinger TLS, Morris JC, Bateman RJ, Breitner JCS, Poirier J, Vachon-Presseau E, Villeneuve S
Corporate AuthorsAlzheimer’s Disease Neuroimaging Initiative(ADNI), Dominantly Inherited Alzheimer Network(DIAN) Study Group, Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer’s Disease(PREVENT-AD) Research Group
JournalNat Commun
Date Published2021 09 09
KeywordsAdult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Amyloid beta-Peptides, Brain, Brain Mapping, Cognitive Dysfunction, Female, Genetic Predisposition to Disease, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Positron-Emission Tomography, Young Adult

Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer's disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of AD, as well as beta-amyloid (Aβ) pathology, can accelerate brain aging. Using data from 1340 cognitively unimpaired participants between 18-94 years of age from multiple sites, we showed that topological properties of graphs constructed from rs-fMRI can predict chronological age across the lifespan. Application of our predictive model to the context of pre-clinical AD revealed that the pre-symptomatic phase of autosomal dominant AD includes acceleration of functional brain aging. This association was stronger in individuals having significant Aβ pathology.

Alternate JournalNat Commun
PubMed ID34504080
PubMed Central IDPMC8429427
Grant ListU01 AG024904 / AG / NIA NIH HHS / United States
U19 AG032438 / AG / NIA NIH HHS / United States
PJT-148963 / / CIHR / Canada