Background Apolipoprotein E (APOE) ε4 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 ε4 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 ε4 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 ε4 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 ε4 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.
Background APOE ε4 is the single most important genetic risk factor for cognitive impairment and Alzheimer disease. While its interaction with lifestyle profile on cognition has been controversial and a recent study indicated that healthy lifestyle profiles only showed its benefits among APOE ε4 non‐carriers among those elderly aged over 65 years old. Accordingly, we examined the association between the APOE genotype and cognitive impairment and its interaction with lifestyle profiles among Chinese oldest old (aged over 80 years old). Method APOE ε4 is the single most important genetic risk factor for cognitive impairment and Alzheimer disease. While its interaction with lifestyle profile on cognition has been controversial and a recent study indicated that healthy lifestyle profiles only showed its benefits among APOE ε4 non‐carriers among those elderly aged over 65 years old. Accordingly, we examined the association between the APOE genotype and cognitive impairment and its interaction with lifestyle profiles among Chinese oldest old (aged over 80 years old). Result Among the 6,160 participants, 57.6% were women and 17.5% were APOE ε4 carriers, with a mean age of 90.1 (SD 7.2) years. The mean MMSE score was 23.3 (SD: 0.4) and 18.2% of the participants had cognitive impairment at baseline. Carrying APOE e4 allele was associated with 22% higher odds (95% CI: 1.02‐1.46) of cognitive impairment. Compared with those with unhealthy lifestyle score, participants with healthy lifestyle score were associated with a 38% (95% CI: 23% ‐ 50%) lower odds of cognitive impairment. No significant interaction between APOE genotype and lifestyle profiles was observed. The association between lifestyle profiles and cognitive function did not vary by APOE genotype. Conclusion APOE genotype and lifestyle profiles were associated with cognitive function among Chinese oldest old, respectively and healthier lifestyle is associated with lower odds of cognitive impairment regardless of APOE genotype.
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