Apolipoprotein E and Health in Older Men: The Concord Health and Ageing in Men Project.

APOE genotype has been associated with various age-related outcomes including Alzheimer's disease, frailty, and mortality. In this study, the relationship between health, particularly cognitive function, and APOE was investigated in older men from the Concord Health and Ageing in Men Project (n = 1,616; age 76.9 ± 5.5 years [range 70-97 years]; Australia). Baseline characteristics and survival up to 12 years were determined. Frailty was measured using Cardiovascular Health study (CHS) criteria and Rockwood frailty index, and cognition using Mini-Mental State Examination (MMSE) and Addenbrookes Cognitive Examination. APOE ε4 was less common in the oldest men and those born in Mediterranean countries. APOE ε2 was beneficially associated with cholesterol, creatinine, gamma-glutamyl transaminase, glucose, and HDL cholesterol while APOE ε4 was adversely associated with cholesterol and albumin. APOE ε4 was associated with a clinical diagnosis of Alzheimer's disease when adjusted for age and region of birth (ε4 homozygotes Odds ratio (OR) 7.0; ε4 heterozygotes OR 2.4, p < .05), and APOE ε2 had a small positive association with cognition. On multivariate regression, overall cognitive function in the entire cohort was associated with age, country of birth, education, and frailty (all p < .001). APOE was not associated with frailty or survival. In conclusion, age and region of birth influenced distribution of APOE genotype in older men. Although APOE ε4 was associated with Alzheimer's disease, overall cognitive function in the cohort was associated more strongly with frailty than APOE genotype.