Association of Unhealthy Lifestyle and Genetic Risk Factors With Mild Cognitive Impairment in Chinese Older Adults
Authors: Duan Huilian , Zhou Dezheng , Xu Ning , Yang Tong , Wu Qi , Wang Zehao , Sun Yue , Li Zhenshu , Li Wen , Ma Fei , Chen Yongjie , Du Yue , Zhang Meilin , Yan Jing , Sun Changqing , Wang Guangshun , Huang Guowei 
Published: July 2023

ImportanceApolipoprotein E polymorphism ε4 (APOE ε4) and methylenetetrahydrofolate reductase (MTHFR) TT genotype are genetic risk factors of mild cognitive impairment (MCI), but whether this risk can be changed by modifiable lifestyle factors is unknown.ObjectiveTo explore whether unhealthy lifestyle (unhealthy dietary intake, current smoking, nonlimited alcohol consumption, and irregular physical activities) is associated with a higher risk of age-related MCI considering genetic risk.Design, Setting, and ParticipantsThis population-based cohort study used data from Tianjin Elderly Nutrition and Cognition (TENC) study participants, recruited from March 1, 2018, through June 30, 2021, and followed up until November 30, 2022. Participants were Chinese adults aged 60 years or older who completed the neuropsychological assessments, general physical examinations, and a personal interview.ExposuresHealthy lifestyle was defined according to the Chinese Dietary Guidelines 2022, including healthy diet, regular physical activity, limited alcohol consumption, and no current smoking, categorized into healthy and unhealthy lifestyles according to weighted standardized lifestyle score. Genetic risk was defined by MTHFR TT genotype and APOE ε4, categorized into low and high genetic risk according to weighted standardized genetic risk score.Main Outcomes and MeasuresThe main outcome was newly diagnosed MCI as identified using a modified version of Petersen criteria. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazard regression models.ResultsA total of 4665 participants were included (mean [SD] age, 67.9 [4.9] years; 2546 female [54.6%] and 2119 male [45.4%]); 653 participants with new-onset MCI (mean [SD] age, 68.4 [5.4] years; 267 female [40.9%] and 386 male [59.1%]) were identified after a median follow-up of 3.11 years (range, 0.82-4.61 years). Individuals with a low genetic risk and an unhealthy lifestyle (HR, 3.01; 95% CI, 2.38-3.79), a high genetic risk and a healthy lifestyle (HR, 2.65; 95% CI, 2.03-3.44), and a high genetic risk and an unhealthy lifestyle (HR, 3.58; 95% CI, 2.73-4.69) had a higher risk of MCI compared with participants with a low genetic risk and a healthy lifestyle. There was a synergistic interaction between lifestyle categories and genetic risk (β = 3.58; 95% CI, 2.73-4.69).Conclusions and RelevanceIn this cohort study of TENC participants, the findings show that unhealthy lifestyle and high genetic risk were significantly associated with a higher risk of MCI among Chinese older adults. Unhealthy lifestyle factors were associated with a higher risk of MCI regardless of genetic risk, and lifestyle and genetic risk had synergistic interactions. These findings could contribute to the development of dietary guidelines and the prevention of early-stage dementia.