Generalization of memory-related brain function in asymptomatic older women with a family history of late onset Alzheimer's Disease: Results from the PREVENT-AD Cohort

Neurobiol Aging. 2021 Aug;104:42-56. doi: 10.1016/j.neurobiolaging.2021.03.009. Epub 2021 Apr 1.


Late-onset Alzheimer's disease (AD) disproportionately affects women compared to men. Episodic memory decline is one of the earliest and most pronounced deficits observed in AD. However, it remains unclear whether sex influences episodic memory-related brain function in cognitively intact older adults at risk of developing AD. Here we used task-based multivariate partial least squares analysis to examine sex differences in episodic memory-related brain activity and brain activity-behavior correlations in a matched sample of cognitively intact older women and men with a family history of AD from the PREVENT-AD cohort study in Montreal, Canada (Mage=63.03±3.78; Meducation=15.41±3.40). We observed sex differences in task-related brain activity and brain activity-behavior correlations during the encoding of object-location associative memories and object-only item memory, and the retrieval of object only item memories. Our findings suggest a generalization of episodic memory-related brain activation and performance in women compared to men. Follow up analyses should test for sex differences in the relationship between brain activity patterns and performance longitudinally, in association with risk factors for AD development. This article is part of the Virtual Special Issue titled COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at

Keywords: Alzheimer's disease; Apolipoprotein E ε4 polymorphism; Associative learning; Brain-behavior relationships; Dedifferentiation; Episodic memory; Familial history; Partial least squares analysis; Sex differences; Task-related functional MRI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology*
  • Alzheimer Disease / psychology
  • Apolipoproteins E / genetics
  • Asymptomatic Diseases*
  • Brain / diagnostic imaging
  • Brain / physiopathology*
  • Cognition*
  • Cohort Studies
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory, Episodic*
  • Middle Aged
  • Sex Characteristics


  • Apolipoproteins E

Grant support