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.