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

Authors

Julie Gonneaud, Institut Universitaire en Santé Mentale Douglas
Alex T. Baria, Institut Universitaire en Santé Mentale Douglas
Alexa Pichet Binette, Institut Universitaire en Santé Mentale Douglas
Brian A. Gordon, Washington University School of Medicine in St. Louis
Jasmeer P. Chhatwal, Massachusetts General Hospital
Carlos Cruchaga, Washington University School of Medicine in St. Louis
Mathias Jucker, Hertie-Institut für klinische Hirnforschung
Johannes Levin, Ludwig-Maximilians-Universität München
Stephen Salloway, Butler Hospital
Martin Farlow, Indiana University School of Medicine
Martin Farlow, Indiana University School of Medicine
Serge Gauthier, Institut Universitaire en Santé Mentale Douglas
Tammie L.S. Benzinger, Washington University School of Medicine in St. Louis
John C. Morris, Washington University School of Medicine in St. Louis
Randall J. Bateman, Washington University School of Medicine in St. Louis
John C.S. Breitner, Institut Universitaire en Santé Mentale Douglas
Judes Poirier, Institut Universitaire en Santé Mentale Douglas
Etienne Vachon-Presseau, Institut Universitaire en Santé Mentale Douglas
Sylvia Villeneuve, Institut Universitaire en Santé Mentale Douglas
Michael Weiner, University of California, San Francisco
Howard J. Rosen, University of California, San Francisco
Bruce L. Miller, University of California, San Francisco
Paul Aisen, University of California, San Diego
Ronald G. Thomas, University of California, San Diego
Michael Donohue, University of California, San Diego
Sarah Walter, University of California, San Diego
Devon Gessert, University of California, San Diego
Tamie Sather, University of California, San Diego
Gus Jiminez, University of California, San Diego
Ronald Petersen, Mayo Clinic
Clifford R. Jack, Mayo Clinic
Matthew Bernstein, Mayo Clinic
Bret Borowski, Mayo Clinic
Jeff Gunter, Mayo Clinic

Document Type

Article

Publication Date

12-1-2021

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.

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