Apolipoprotein E genotype, dementia, and mortality in the oldest old: the 90+ Study

Although the apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer's disease (AD), it is not clear whether this relationship persists among the oldest old. Several European studies suggest that the effect of the APOE ε4 allele on dementia and mortality disappears in very old age. We describe the APOE allele and genotype frequencies and examine whether the presence of the APOE ε4 or APOE ε2 alleles is related to prevalent dementia, incident dementia, and mortality in a population-based cohort of oldest-old participants in the United States.

We studied 904 participants aged 90 years and older from The 90+ Study. Eight hundred two (89%) participants were genotyped and included in the prevalent dementia and mortality analyses. The 520 initially nondemented participants were included in the incident dementia analyses and were evaluated for dementia every 6 months.

The APOE ε4 allele was significantly associated with prevalent dementia (odds ratio = 2.06) and AD (odds ratio = 2.37) in women but not in men. The APOE ε2 allele was not related to prevalent dementia in either sex. After an average follow-up of 2.4 years, 188 incident dementia cases were identified. Neither the APOE ε4 nor the APOE ε2 allele was related to incident dementia or AD. Five hundred ten (64%) participants died after an average follow-up of 2.3 years, and their mortality was not related to the presence of either the APOE ε2 or APOE ε4 allele.

Our findings suggest that the associations between APOE ε4, dementia, and mortality are age dependent, and that APOE ε4 no longer plays a role in dementia and mortality at very old ages.