Functional brain age prediction suggests accelerated aging in preclinical familial Alzheimer's disease, irrespective of fibrillar amyloid-beta pathology

Julie Gonneaud; Alex T. Baria; Alexa Pichet Binette; Brian Andrew Gordon; Jasmeer P. Chhatwal; Carlos Cruchaga; Mathias Jucker; Johannes Levin; Stephen Salloway; Martin Rhys Farlow; Serge G. Gauthier; Tammie L.S. Benzinger; John C. Morris; Randall John Bateman; John C.S. Breitner; Judes Poirier; Étienne Vachon‐Presseau; Sylvia Villeneuve; Alzheimer’s Disease Neuroimaging Initiative; The Dominantly Inherited Alzheimer Network (DIAN)

doi:10.1101/2020.05.06.076745

NeurosciencebioRxivMay 6, 2020

Preprint

Functional brain age prediction suggests accelerated aging in preclinical familial Alzheimer's disease, irrespective of fibrillar amyloid-beta pathology

Julie Gonneaud iD, Alex T. Baria, Alexa Pichet Binette iD, Brian Andrew Gordon iD, Jasmeer P. Chhatwal iD, Carlos Cruchaga iD, Mathias Jucker iD, Johannes Levin iD, Stephen Salloway iD, Martin Rhys Farlow iD, Serge G. Gauthier iD, Tammie L.S. Benzinger iD, John C. Morris iD, Randall John Bateman iD, John C.S. Breitner iD, Judes Poirier iD, Étienne Vachon‐Presseau iD, Sylvia Villeneuve iD, Alzheimer’s Disease Neuroimaging Initiative, The Dominantly Inherited Alzheimer Network (DIAN)

Abstract

We aimed at developing a model able to predict brain aging from resting state functional connectivity (rs-fMRI) and assessing whether genetic risk/determinants of Alzheimers disease (AD) and amyloid (A{beta}) pathology contributes to accelerated brain aging. Using data collected in 1340 cognitively unimpaired participants from 18 to 94 years old selected across multi-site cohorts, we showed that chronological age can be predicted across the whole lifespan from topological properties of graphs constructed from rs-fMRI. We subsequently used the difference between the model-predicted age and the chronological age in pre-symptomatic autosomal dominant AD (ADAD) mutation carriers and asymptomatic individuals at risk of sporadic AD and assessed the influence of genetics and A{beta} pathology on brain age. Applying our predictive model in the context of preclinical AD revealed that the pre-symptomatic phase of ADAD is characterized by accelerated functional brain aging. This phenomenon is independent from, and might precede, detectable fibrillar A{beta} deposition.

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