Objectives: We tested the hypothesis that neuroticism moderates the association between APOE (apolipoprotein E) genotype and two major outcomes, cognitive function and Alzheimer disease. We also explored whether other personality dimensions (extraversion, openness to experience, agreeableness, and conscientiousness) moderate the associations of APOE with these outcomes.
Design: Primary analyses of existing randomized clinical trial data.
Sample: Six-hundred two older adults (mean age of 78 years at baseline).
Measurements: APOE genotype, the NEO-Five Factor Inventory, the Alzheimer's Disease Assessment Scale-Cognitive: measured every 6 months for 6.5 years) and relevant covariates.
Results: Fully adjusted multivariate analyses showed that the association between the presence of APOE [Latin Small Letter Open E]-4 allele(s) and both outcomes was evident among individuals with high levels of neuroticism and extraversion but not among persons with low levels of these traits.
Conclusions: Phenotypic personality dimensions, primarily neuroticism and extraversion, moderate the relationship between APOE [Latin Small Letter Open E]-4 genotype and cognitive outcomes among older adults. Future research is needed to elucidate the physiological processes involved in these particular phenotype-genotype interactions.