The Apolipoprotein E ϵ4 Allele and Decline in Different Cognitive Systems During a 6-Year Period

CONTEXT: Impairment of episodic memory is an early and defining feature of Alzheimer disease (AD). The apolipoprotein E (APOE) epsilon 4 allele is known to influence risk of AD but it has been difficult to establish whether it affects episodic memory differently from other cognitive functions. OBJECTIVE: To examine the association of epsilon 4 with decline in different cognitive systems. DESIGN: Longitudinal cohort study. SETTING: More than 40 groups of Catholic clergy from across the United States. PARTICIPANTS: Older Catholic clergy members without clinical evidence of dementia at baseline underwent annual clinical evaluations for up to 6 years. Of 624 persons eligible for follow-up, 611 (98%) participated, of whom 161 (26%) had at least 1 epsilon 4 allele. They completed an average of 5.5 evaluations (range, 2-7). MAIN OUTCOME MEASURES: Incident AD and annual rates of change in episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. RESULTS: The presence of epsilon 4 was associated with risk of developing AD on follow-up (relative risk, 1.92; 95% confidence interval, 1.27-2.89). In a series of random effects models, epsilon 4 was associated with impaired baseline function in episodic memory and visuospatial ability and with more rapid decline in all domains. The effect of epsilon 4 on annual decline in episodic memory (>3-fold increase) was significantly stronger than its effect on decline in other cognitive systems (P<.01), and at baseline, its effect on episodic memory was marginally stronger than its effect on other cognitive domains (P =.06). CONCLUSION: The results suggest that the APOE epsilon 4 allele influences risk of AD by a relatively selective effect on episodic memory.