Sex-Based Memory Advantages and Cognitive Aging: A Challenge to the Cognitive Reserve Construct?

Richard J. Caselli, Amylou C. Dueck, Dona E.C. Locke, Leslie C. Baxter, Bryan K. Woodruff, Yonas E. Geda

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Education and related proxies for cognitive reserve (CR) are confounded by associations with environmental factors that correlate with cerebrovascular disease possibly explaining discrepancies between studies examining their relationships to cognitive aging and dementia. In contrast, sex-related memory differences may be a better proxy. Since they arise developmentally, they are less likely to reflect environmental confounds. Women outperform men on verbal and men generally outperform women on visuospatial memory tasks. Furthermore, memory declines during the preclinical stage of AD, when it is clinically indistinguishable from normal aging. To determine whether CR mitigates age-related memory decline, we examined the effects of gender and APOE genotype on longitudinal memory performances. Memory decline was assessed in a cohort of healthy men and women enriched for APOE ε4 who completed two verbal [Rey Auditory Verbal Learning Test (AVLT), Buschke Selective Reminding Test (SRT)] and two visuospatial [Rey-Osterrieth Complex Figure Test (CFT), and Benton Visual Retention Test (VRT)] memory tests, as well as in a separate larger and older cohort [National Alzheimer's Coordinating Center (NACC)] who completed a verbal memory test (Logical Memory). Age-related memory decline was accelerated in APOE ε4 carriers on all verbal memory measures (AVLT, p=.03; SRT p<.001; logical memory p<.001) and on the VRT p=.006. Baseline sex associated differences were retained over time, but no sex differences in rate of decline were found for any measure in either cohort. Sex-based memory advantage does not mitigate age-related memory decline in either APOE ε4 carriers or non-carriers.

Original languageEnglish (US)
Pages (from-to)95-104
Number of pages10
JournalJournal of the International Neuropsychological Society
Issue number2
StatePublished - Mar 16 2015
Externally publishedYes


  • APOE
  • Aging
  • Memory
  • Mild cognitive impairment
  • Preclinical Alzheimer's disease
  • Sex and cognition

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Clinical Neurology
  • Psychiatry and Mental health


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