Association of APOE ε4 genotype and lifestyle with cognitive function among Chinese adults aged 80 years and older: A cross-sectional study

Author summary Why was this study done? Both genetic and lifestyle factors have impact on cognitive function among older adults, but previous studies showed inconsistent results on the interaction between lifestyle profiles and genetic risk on cognition. One recent study found that healthy lifestyle profiles were associated with lower risks of dementia only among apolipoprotein E () epsilon 4 noncarriers, but not among carriers. However, relationships between epsilon 4 carrier status, lifestyle factors, and cognitive function are not well understood for the oldest group of older adults. What did the researchers do and find? We used data from 6,160 participants 80 years or older from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) with information on genotype, lifestyles, and cognition. We defined lifestyle profile by a healthy lifestyle score including smoking, alcohol consumption, body weight, dietary pattern, and physical activity. Both healthy lifestyle profile and lower genetic dementia risk, represented by not carrying the epsilon 4 allele, were associated with lower odds of cognitive impairment. No interaction between epsilon 4 genotype and lifestyle profiles was observed. What do these findings mean? Our results suggest the importance of a healthier lifestyle for cognition regardless of genetic dementia risk and increases our understanding of this relationship in the oldest older adults (80 years and older). The main limitation of our study is that our data are cross-sectional and thus validation by cohort studies or trials are needed. Background Apolipoprotein E (APOE) epsilon 4 is the single most important genetic risk factor for cognitive impairment and Alzheimer disease (AD), while lifestyle factors such as smoking, drinking, diet, and physical activity also have impact on cognition. The goal of the study is to investigate whether the association between lifestyle and cognition varies by APOE genotype among the oldest old. Methods and findings We used the cross-sectional data including 6,160 oldest old (aged 80 years old or older) from the genetic substudy of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) which is a national wide cohort study that began in 1998 with follow-up surveys every 2-3 years. Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score less than 18. Healthy lifestyle profile was classified into 3 groups by a composite measure including smoking, alcohol consumption, dietary pattern, physical activity, and body weight. APOE genotype was categorized as APOE epsilon 4 carriers versus noncarriers. We examined the associations of cognitive impairment with lifestyle profile and APOE genotype using multivariable logistic regressions, controlling for age, sex, education, marital status, residence, disability, and numbers of chronic conditions. The mean age of our study sample was 90.1 (standard deviation [SD], 7.2) years (range 80-113); 57.6% were women, and 17.5% were APOE epsilon 4 carriers. The mean MMSE score was 21.4 (SD: 9.2), and 25.0% had cognitive impairment. Compared with those with an unhealthy lifestyle, participants with intermediate and healthy lifestyle profiles were associated with 28% (95% confidence interval [CI]: 16%-38%, P < 0.001) and 55% (95% CI: 44%-64%, P < 0.001) lower adjusted odds of cognitive impairment. Carrying the APOE epsilon 4 allele was associated with 17% higher odds (95% CI: 1%-31%, P = 0.042) of being cognitively impaired in the adjusted model. The association between lifestyle profiles and cognitive function did not vary significantly by APOE epsilon 4 genotype (noncarriers: 0.47 [0.37-0.60] healthy versus unhealthy; carriers: 0.33 [0.18-0.58], P for interaction = 0.30). The main limitation was the lifestyle measurements were self-reported and were nonspecific. Generalizability of the findings is another limitation because the study sample was from the oldest old in China, with unique characteristics such as low body weight compared to populations in high-income countries. Conclusions In this study, we observed that healthier lifestyle was associated with better cognitive function among the oldest old regardless of APOE genotype. Our findings may inform the cognitive outlook for those oldest old with high genetic risk of cognitive impairment.