Sex differences in the association of the apolipoprotein E epsilon 4 allele with incidence of dementia, cognitive impairment, and decline

Neurobiol Aging. 2012 Apr;33(4):720-731.e4. doi: 10.1016/j.neurobiolaging.2010.05.017. Epub 2010 Jul 8.

Abstract

We examined longitudinal associations between the apolipoprotein E ε4 allele (ApoE4(+) status) and several cognitive outcomes and tested effect modification by sex. Data on 644 non-Hispanic Caucasian adults, from the Baltimore Longitudinal Study of Aging (BLSA) were used. Dementia onset, cognitive impairment and decline were assessed longitudinally. After 27.5 years median follow-up, 113 participants developed dementia. ApoE4(+) predicted dementia significantly (hazard ratio [HR] = 2.89; 95% confidence interval [CI], 1.93-4.33), with nonsignificant sex differences. Taking all time points for predicting cognition, women had significantly stronger positive associations than men between ApoE4(+) status and impairment or decline on the California Verbal Learning Test (CVLT; delayed recall and List A total recall) and on Verbal Fluency Test-Categories. This ApoE4 × sex interaction remained significant with Bonferroni correction only for CVLT-delayed recall. Taking time points prior to dementia for cognitive predictions, the positive association between impairment in CVLT-delayed recall and ApoE4(+) status remained stronger among women, though only before Bonferroni correction. While ApoE4(+) status appears to be a sex neutral risk factor for dementia, its association with verbal memory and learning decline and impairment was stronger among women.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Apolipoprotein E4 / genetics*
  • Cognition Disorders / epidemiology*
  • Cognition Disorders / genetics*
  • Cognition Disorders / mortality
  • Dementia / epidemiology*
  • Dementia / genetics*
  • Dementia / mortality
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genotype
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Longitudinal Studies
  • Male
  • Mental Recall / physiology
  • Middle Aged
  • Neuropsychological Tests
  • Psychiatric Status Rating Scales
  • Sex Characteristics*
  • Surveys and Questionnaires
  • Young Adult

Substances

  • Apolipoprotein E4