Impact of the Apolipoprotein E ε4 Allele on the Relationship Between Healthy Lifestyle and Cognitive Decline: A Population-Based Study

Abstract

Adherence to a healthy lifestyle-characterized by abstaining from smoking, being physically and cognitively active, having a high-quality diet, and limiting alcohol use-is associated with slower cognitive decline in older adults, but whether this relationship extends to persons with a genetic predisposition (e.g., carriers of the ε4 allele of the apolipoprotein E gene (APOE*E4)) remains uncertain. Using data from a population-based study, the Chicago Health and Aging Project (Chicago, Illinois), we followed 3,886 individuals who underwent regular clinical and cognitive assessments from 1993 to 2012. Of 3,886 older adults, 1,269 (32.7%) were APOE*E4 carriers. Compared with noncarriers, APOE*E4 carriers had faster cognitive decline (β = -0.027 units/year, 95% confidence interval (CI): -0.032, -0.023). In contrast, persons with 2-3 and 4-5 healthy lifestyle factors had slower cognitive decline (β = 0.008 units/year (95% CI: 0.002, 0.014) and β = 0.019 units/year (95% CI: 0.011, 0.026), respectively) compared with those with 0-1 factor. In analyses stratified by APOE*E4 status, adherence to a healthy lifestyle (e.g., 4-5 factors vs. 0-1 factors) was associated with a slower rate of cognitive decline in both APOE*E4 carriers (β = 0.029, 95% CI: 0.013, 0.045) and noncarriers (β = 0.013, 95% CI: 0.005, 0.022). These results underscore the impact of a healthy lifestyle on cognition, particularly among persons with a genetic predisposition, who are more vulnerable to cognitive decline as they age.

Keywords: APOE ε4 allele; Alzheimer dementia; apolipoprotein E; apolipoprotein E gene; cognitive dysfunction; diet; exercise; health behavior.

Figure 1

Rate of change in global cognitive score over 17 years among carriers of the ε4 allele of the apolipoprotein E gene (APOE^*E4) (A) and APOE^*E4 noncarriers (B) according to their adherence to healthy lifestyle factors, Chicago Health and Aging Project, 1993–2012. A behavior was classified as “healthy” if it met the following criterion: 1) MIND diet score (without alcohol) in the top 40% of the cohort distribution; 2) cognitive activities in the top 40% of the cohort distribution; 3) not being a current smoker; 4) moderate or vigorous exercise for ≥150 minutes/week; and 5) light-to-moderate alcohol consumption (1–15 g/day for women and 1–30 g/day for men). APOE^*E4 carriers with 0–1 healthy lifestyle factors had a rate of cognitive change of −0.116 units/year, and those with 4–5 healthy factors had a rate of −0.087 units/year. APOE^*E4 noncarriers with 0–1 healthy lifestyle factors had a rate of cognitive change of −0.071 units/year, and those with 4–5 healthy factors had a rate of −0.058 units/year. MIND, Mediterranean-DASH Diet Intervention for Neurodegenerative Delay.