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

Nat Commun. 2021 Sep 9;12(1):5346. doi: 10.1038/s41467-021-25492-9.

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain Mapping / methods
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / metabolism*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Mutation
  • Positron-Emission Tomography / methods
  • Young Adult

Substances

  • Amyloid beta-Peptides