Impact of sex and APOE ε4 on the association of cognition and hippocampal volume in clinically normal, amyloid positive adults

Kellen K. Petersen, Ellen Grober, Richard B. Lipton, Reisa A. Sperling, Rachel F. Buckley, Paul S. Aisen, Ali Ezzati

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Cognitive decline follows pathological changes including neurodegeneration on the Alzheimer's disease continuum. However, it is unclear which cognitive domains first become affected by neurodegeneration in amyloid-positive individuals and if sex or apolipoprotein (APOE) ε4 status differences affect this relationship. Methods: Data from 1233 cognitively unimpaired, amyloid-positive individuals 65 to 85 years of age were studied to assess the effect of hippocampal volume (HV) on cognition and to evaluate differences due to sex and APOE ε4 status. Results: Lower HV was linked with worse performance on measures of memory (free recall, total recall, logical memory delayed recall, Mini-Mental State Examination [MMSE]), executive functioning (digit symbol substitution, DSS), and the Preclinical Alzheimer's Cognitive Composite (PACC). Among both women and APOE ε4+ individuals, all cognitive measures, except MMSE, were associated with HV. DSS and PACC had the largest effect sizes in differentiating early and intermediate stage neurodegeneration. Discussion: Despite all cognitive measures being associated with HV, cognitive tests show differences in detecting early or late signs of neurodegeneration. Differences exist in association between cognition and neurodegeneration based on sex and APOE ε4 status.

Original languageEnglish (US)
Article numbere12271
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume14
Issue number1
DOIs
StatePublished - 2022

Keywords

  • APOE ε4
  • cognition
  • FCSRT96
  • hippocampal volume
  • logical memory
  • MMSE
  • PACC
  • Sex

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health

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