OBJECTIVES: To assess the risk of death in relation to apolipoprotein E (APOE) genotype and to evaluate how APOE genotype interacts with dementia and with other major medical conditions to affect survival.
DESIGN: A 6-year prospective cohort study of dementia, APOE genotype and survival.
SETTING: Health maintenance organization in southern California.
PARTICIPANTS: One thousand eight hundred forty-two white women aged 75 and older.
MEASUREMENTS: Dementia was determined using a multistage assessment procedure, medical record, and death certificate review.
RESULTS: With women with the APOE 3/3 genotype as the referent, age-adjusted hazard ratios (HRs) for death according to genotype were 1.25 (95% confidence interval (CI)=1.00–1.56) for APOE 2/4, 3/4, or 4/4 and 0.83 (95% CI=0.62–1.13) for APOE 2/3 or 2/2. Survival was associated with APOE genotype (log rank test P=.02). Women with the APOE 2/4, 3/4, or 4/4 genotype died at an earlier age, and those with APOE 2/2 or 2/3 died later than those with the APOE 3/3 genotype. After adjustment for age, education, and hormone use, HRs for death were significantly higher in women with the APOE 2/4, 3/4, or 4/4 genotype who developed dementia (HR=3.74; 95% CI=2.81–4.99) and the APOE 2/3 genotype (HR=3.23; 95%=CI=1.97–5.28) than in women without dementia and the APOE 3/3 genotype. The HRs for death were greater with other medical conditions, but no interaction with any APOE genotype was found.
CONCLUSION: In this population of elderly women, although having at least one ɛ4 allele increased the chances of an earlier death, having dementia increased the risk of death regardless of APOE genotype.