Objective: The apolipoprotein (APOE) epsilon4 allele genotype is a risk factor for dementia, but not all people with the APOE epsilon4 allele develop cognitive impairment (CI). Among participants with the APOE epsilon4 allele (N = 664), we identified biological, psychological, and social variables that discriminate between participants who develop CI from those who do not. We then determined if these variables predicted CI in noncarriers (N = 1421). In the sample as a whole we then determined if each of these identified variables moderate the relationship between the APOE epsilon4 allele and CI.
Methods: We used data from a biracial community-dwelling sample of older adults. Data were collected at four time points over a 10-year period. Cognitive functioning was assessed at each wave, using the Short Portable Mental Status Questionnaire (SPMSQ). APOE genotyping was performed at Wave 3.
Results: Among APOE epsilon4 allele carriers, but not noncarriers, variables associated with CI included white race, female gender, low BMI, number of negative life events, and health problems (high blood pressure, heart disease, and stroke). In analyses testing for moderate effects and including the entire sample, significant interactions with APOE epsilon4 allele and predictor variables revealed that white race, low BMI, stroke, heart disease, and negative life events had a greater effect on CI among those with the APOE epsilon4 allele compared to those without the allele.
Conclusion: There are biological, psychological, and social variables associated with increased risk for CI among individuals with the APOE epsilon4 allele.