Cognitive Activities, Lifestyle Factors, and Risk of Cognitive Impairment, with an Analysis of the Apolipoprotein Epsilon 4 Genotype

Introduction: Cognitive stimulating activities and a healthy lifestyle are associated with less cognitive impairment. However, whether the association is varied by Apolipoprotein epsilon 4 (APOE ϵ4) allele carrier status remains inconclusive. We aimed to investigate whether the association of cognitively stimulating activities and a healthy lifestyle with the risk of cognitive impairment varied by APOE ϵ4 allele carrier status. Methods: A case-control study was conducted for adults aged 60 years and above. Six province administrative units (Beijing, Shanghai, Hubei, Sichuan, Guangxi, and Yunnan) were included using stratified multistage cluster sampling. A total of 1,300 individuals were identified with cognitive impairment (cases) at enrollment and were matched 1:2 on sex, age (±2 years), and residential district with controls who were cognitively normal at the time of the evaluation. We used a standardized questionnaire to collect information on cognitive stimulating activities, lifestyle factors, demographics, and comorbidity. Cognitive stimulating activities included reading books or newspapers, playing cards or mahjong, using the Internet, socializing with neighbors, and community activities. Lifestyle factors included smoking, alcohol drinking, daily tea drinking, and regular exercise. We used logistic regression to assess the interaction between cognitive stimulating activities, lifestyle factors, and APOE ϵ4 allele carrier status (yes/no) on the risk of cognitive impairment. We tested for additive interaction by estimating relative excess risk (RERI) due to interaction and multiplicative interaction employing the p value of the interaction term of each lifestyle factor and APOE ϵ4 into the model. Results: Four cognitive stimulating activities were associated with less cognitive impairment regardless of APOE ϵ4 status. Using the Internet (odds ratio [OR]: 0.53, 95% confidence interval [CI]: 0.30-0.95), daily tea drinking (OR: 0.79; 95% CI: 0.63-0.98), and regular exercise (OR: 0.78; 95% CI: 0.65-0.94) were associated with less cognitive impairment only in noncarriers. Multiplicative and additive interactions were found between community activities and APOE ϵ4 carrier status (multiplicative p value = 0.03; RERI 0.738, 95% CI: 0.201-1.275). Conclusion: The associations between cognitive activities and cognitive impairment were robust regardless of the APOE ϵ4 carrier status, while the associations between lifestyle factors and cognitive impairment varied by APOE ϵ4 carrier status.