The APOE ε4 Allele Is Associated with Incident Mild Cognitive Impairment among Community-Dwelling Older Persons

Abstract

Background: The apolipoprotein E (APOE) ε4 allele is a well-known risk factor for the development of Alzheimer’s disease, but little is known about the association of the ε4 allele with incident mild cognitive impairment (MCI). Objective: Test the hypothesis that the ε4 allele is associated with an increased risk of developing MCI. Methods: More than 600 older Catholic clergy members from the Religious Orders Study without any cognitive impairment at baseline underwent APOE genotyping and detailed annual clinical evaluations for up to 16 years of follow-up (mean: 10.17 years; range: 2–16 years) to document incident MCI and rates of decline in global cognition and 5 cognitive domains (i.e. episodic memory, semantic memory, working memory, perceptual speed and visuospatial abilities). Results: During up to 16 years of annual follow-up, 339 of 607 persons (56%) developed MCI. In a proportional hazards model adjusted for age, sex and education, the presence of the APOE ε4 allele was associated with a 1.4-fold increased risk of incident MCI (hazard ratio: 1.36; 95% CI: 1.04, 1.78). Further, this association persisted in analyses that required MCI to persist for at least one year (hazard ratio: 1.50; 95% CI: 1.05, 2.14). Finally, the ε4 allele was associated with an increased rate of decline in global cognition and 4 out of 5 cognitive systems (i.e. episodic memory, semantic memory, working memory and perceptual speed). Conclusion: The presence of the APOE ε4 allele is associated with an increased risk of MCI and a more rapid rate of cognitive decline in old age.