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 R. Farlow, Serge Gauthier, Tammie L.S. Benzinger, John C. Morris, Randall J. Bateman, John C.S. Breitner, Judes Poirier, Étienne Vachon‐Presseau, Sylvia Villeneuve, Alzheimer’s Disease Neuroimaging Initiative (ADNI), Michael Weiner, Howard J. Rosen, Bruce L. Miller, Paul Aisen, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Ronald C. Petersen, Clifford R. Jack, Matt A. Bernstein, Bret Borowski, Jeff Gunter, Matthew L. Senjem, Prashanthi Vemuri, David T. Jones, Kejal Kantarci, Chad Ward, Sara S. Mason, Colleen S. Albers, David S. Knopman, Kris Johnson, William J. Jagust, Susan Landau, John Q. Trojanowki, Arthur W. Toga, Karen Crawford, Scott Neu, Laurel Beckett, Danielle Harvey, Charles DeCarli, Robert C. Green, Andrew J. Saykin, Tatiana M. Foroud, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Scott Herring, Cynthia Hunt, Nigel J. Cairns, Erin Householder, Lisa Taylor Reinwald, Leslie M. Shaw, Steven E. Arnold, Jason Karlawish, S. J. Wolk, Enchi Liu, Tom Montine, Nick C. Fox, Paul M. Thompson, Norbert Schuff, Robert A. Koeppe, Judith L. Heidebrink, Joanne Lord, Norm Foster, Eric M. Reiman, Kewei Chen, Adam Fleisher, Pierre N. Tariot, Stephanie Reeder, Chet Mathis, Oscar L. López, MaryAnn Oakley, Donna M. Simpson, Virginia Lee, Magdalena Korecka, Michal Figurski, Steven Potkin, Zaven Kachaturian, Richard Frank, Peter J. Snyder, Susan Molchan, Jeffrey Kaye, Joseph F. Quinn, Betty Lind
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.