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

Julie Gonneaud (), Alex T. Baria, Alexa Pichet Binette, Brian A. Gordon, Jasmeer P. Chhatwal, Carlos Cruchaga, Mathias Jucker, Johannes Levin, Stephen Salloway, Martin Farlow, Serge Gauthier, Tammie L. S. Benzinger, John C. Morris, Randall J. Bateman, John C. S. Breitner, Judes Poirier, Etienne Vachon-Presseau and Sylvia Villeneuve ()
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Julie Gonneaud: McGill University
Alex T. Baria: McGill University
Alexa Pichet Binette: McGill University
Brian A. Gordon: Washington University School of Medicine
Jasmeer P. Chhatwal: Brigham and Women’s Hospital–Massachusetts General Hospital
Carlos Cruchaga: Washington University School of Medicine
Mathias Jucker: University of Tübingen
Johannes Levin: Ludwig-Maximilians-Universität München, German Center for Neurodegenerative Diseases and Munich Cluster for Systems Neurology (SyNergy)
Stephen Salloway: Butler Hospital
Martin Farlow: Indiana University School of Medicine
Serge Gauthier: McGill University
Tammie L. S. Benzinger: Washington University School of Medicine
John C. Morris: Washington University School of Medicine
Randall J. Bateman: Washington University School of Medicine
John C. S. Breitner: McGill University
Judes Poirier: McGill University
Etienne Vachon-Presseau: McGill University
Sylvia Villeneuve: McGill University

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-25492-9

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