Impact of the Apolipoprotein E4 allele on the Relationship Between Healthy Lifestyle and Cognitive Decline: A Population-based Study

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 individuals with a genetic predisposition (e.g., ApoE4 carriers) remains uncertain. From the population-based study, the Chicago Health and Aging Project, we followed 3,886 individuals with regular clinical and cognitive assessments from 1993 to 2012. Of 3,886 older adults, 1,269 (32.7%) were ApoE4 carriers. Compared to non-carries, ApoE4 carriers had a faster cognitive decline by -0.027 (95%CI -0.032, -0.023) units per year. In contrast, individuals with 2-3 and 4-5 healthy lifestyle factors had a slower cognitive decline by 0.008 (95%CI 0.002, 0.014) and 0.019 (95%CI 0.011, 0.026) units per year, compared to those with 0-1 factor. In analyses stratified by ApoE4 status, adherence to a healthy lifestyle (e.g., 4-5 vs. 0-1 factors) was associated with a slower rate of cognitive decline in both ApoE4 carriers ($\beta$=0.029 units/year; 95%CI 0.013, 0.045) and non-carriers ($\beta$=0.013, 95%CI 0.005, 0.022). These results underscore the impact of a healthy lifestyle on cognition, particularly among individuals with a genetic predisposition who are more vulnerable to cognitive decline as they age.