Apolipoprotein E genotype impact on memory and attention in older persons: the moderating role of personality phenotype

Int J Geriatr Psychiatry. 2018 Feb;33(2):332-339. doi: 10.1002/gps.4748. Epub 2017 Jun 14.


Objectives: To determine if phenotypic personality traits modify the association of Apolipoprotein E (APOE) genotypes with different domains of cognitive function.

Design: Cross-sectional.

Methods: 172 non-demented older adults were administered the NEO-Five Factor Inventory (NEO-FFI), a battery of neuropsychological tests assessing memory, attention, executive function, language, and visuospatial ability, and underwent APOE genotyping. Multivariate (multiple-dependent variable) regression models predicting cognitive domains tested APOE interactions with personality traits, adjusting for age, sex, and education.

Results: The APOE ε4 allele showed small to modest main effects on memory and executive function (1/3 SD deficits for carriers, p < .05), with ε2 status evidencing minimal and non-significant benefit. Neuroticism interacted with both ε2 and ε4 alleles in associations with attention scores (p = .001), with ε2 benefits and ε4 deficits being marked at high Neuroticism (Mean [M] covariate-adjusted Z-score = .39 for ε2, -.47 for ε4). The association of ε4 with memory was moderated by Conscientiousness (p < .001), such that ε4 memory deficits were apparent at low Conscientiousness (M = -.56), but absent at high levels of Conscientiousness. Weaker patterns (p < .05) also suggested ε4-related detriments in executive function only at lower Conscientiousness, and ε2 memory benefits only at higher Openness.

Conclusions: Conscientiousness and Neuroticism moderate APOE associations with memory and executive function. As such, they may be useful phenotypic markers in refining the prognostic significance of this polymorphism. Effect-modifying personality traits also provide clues about behavioral and psychological factors that influence the cognitive impact of APOE. Copyright © 2017 John Wiley & Sons, Ltd.

Keywords: APOE; attention; memory; personality traits.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apolipoprotein E4 / genetics
  • Apolipoproteins E / genetics*
  • Attention / physiology*
  • Cognition / physiology
  • Cross-Sectional Studies
  • Executive Function / physiology
  • Female
  • Genotype
  • Humans
  • Male
  • Memory / physiology*
  • Memory Disorders / genetics
  • Neuropsychological Tests
  • Personality / genetics*
  • Phenotype
  • Regression Analysis
  • Spatial Navigation / physiology


  • Apolipoprotein E4
  • Apolipoproteins E