Global Health Research Center, Duke Kunshan University, Kunshan, Jiangsu, China.
MindRank AI Ltd., Hangzhou, China.
PLoS Med. 2021 Jun 1;18(6):e1003597. doi: 10.1371/journal.pmed.1003597. eCollection 2021 Jun.
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.
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.
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.
载脂蛋白 E (APOE) ε4 是认知障碍和阿尔茨海默病 (AD) 的最重要的单一遗传风险因素，而生活方式因素，如吸烟、饮酒、饮食和体育活动，也会影响认知。本研究的目的是调查在最年长的老年人中，生活方式与认知之间的关联是否因 APOE 基因型而异。
我们使用了横断面数据，包括来自中国长寿纵向研究（CLHLS）遗传子研究的 6160 名最年长的老年人（年龄在 80 岁或以上），这是一项始于 1998 年的全国性队列研究，每 2-3 年进行一次随访调查。认知障碍定义为简易精神状态检查（MMSE）评分低于 18。健康的生活方式特征通过包括吸烟、饮酒、饮食模式、体育活动和体重在内的综合措施分为 3 组。APOE 基因型分为 APOE ε4 携带者和非携带者。我们使用多变量逻辑回归，控制年龄、性别、教育、婚姻状况、居住地、残疾和慢性病数量，来检查认知障碍与生活方式特征和 APOE 基因型的关系。我们研究样本的平均年龄为 90.1（标准差 [SD]，7.2）岁（范围 80-113）；57.6%为女性，17.5%为 APOE ε4 携带者。平均 MMSE 评分为 21.4（SD：9.2），25.0%的人认知受损。与生活方式不健康的参与者相比，生活方式处于中等和健康状态的参与者认知障碍的调整后比值比分别降低 28%（95%置信区间 [CI]：16%-38%，P<0.001）和 55%（95%CI：44%-64%，P<0.001）。携带 APOE ε4 等位基因与认知障碍的调整后比值比增加 17%（95%CI：1%-31%，P=0.042）。生活方式特征与认知功能之间的关联在 APOE ε4 基因型方面没有显著差异（非携带者：0.47[0.37-0.60]健康与不健康；携带者：0.33[0.18-0.58]，交互作用 P 值=0.30）。主要限制是生活方式测量是自我报告的，且不具体。由于研究样本来自中国最年长的老年人，与高收入国家的人群相比，他们的体重较低，因此存在另一个发现推广的局限性。
在这项研究中，我们观察到，无论 APOE 基因型如何，最年长的老年人中更健康的生活方式与更好的认知功能有关。我们的研究结果可能为那些认知障碍遗传风险高的最年长的老年人提供认知前景。
