There is an association between an unhealthy lifestyle with higher risk of mild cognitive impairment (MCI), according to a recent Chinese study, suggesting lifestyle changes may help to diminish dementia risk in older adults.¹

The existing awareness that apolipoprotein epolymorphismε4 (APOEε4) and methylenetetrahydrofolate reductase (MTHFR) TT genotype are known to be genetic risk factors for those who develop MCI led to the establishment of this new study.²

The investigators wished to examine whether these risk factors are modifiable through alterations in lifestyle. The research was authored by Guowei Huang, PhD, from the Department of Nutrition and Food Science at Tianjin Medical University’s School of Public Health in China.

“In this study, we analyzed longitudinal associations of genetic risk and lifestyle with the incidence of MCI, and the interaction of lifestyle and genetic risk, within the context of the Tianjin Elderly Nutrition and Cognition (TENC) cohort study,” Huang and colleagues wrote. “The purpose of this study was to identify potential intervention targets for MCI and to provide evidence for the optimization of dietary guidelines.”

Background and Findings

The study’s investigators used data gathered from participants in the Tianjin Elderly Nutrition and Cognition (TENC) study, specifically from those who had been enrolled between March 1, 2018, and June 30, 2021, and followed up until November 30, 2022. The study included Chinese adults in the age range of 60 years or older who had undergone neuropsychological assessments, general physical examinations, and personal interviews.

They defined healthy lifestyles based on the guidelines from the Chinese Dietary Guidelines 2022, which encompassed elements such as regular physical activity, a nutritious diet, limited consumption of alcohol, and non-smoking status. The team categorized the participants into groups with either healthy or unhealthy lifestyles, according to their weighted standardized lifestyle scores.

The investigators determined participants’ genetic risk by considering the presence of the MTHFR TT genotype and APOE ε4, and the study’s participants were classified into low and high genetic risk groups based upon their weighted standardized genetic risk scores.

The research team’s primary objective was to find cases of newly diagnosed mild cognitive impairment (MCI) through a modified version of Petersen criteria. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by using Cox proportional hazard regression models to assess the association between lifestyle factors, genetic risk, and the development of MCI.

The investigators reported there were 4665 participants, with a mean age of 67.9 years, included in the team’s study. The group was 54.6% female and 45.4% male, and among them, 653 were found to have developed new-onset MCI during a median follow-up of 3.11 years.

The study results indicated that those with a combination of low genetic risk and an unhealthy lifestyle had a 3.01 times higher MCI risk (95% CI: 2.38 - 3.79) compared to individuals who were found to have low genetic risk and a healthy lifestyle. Similarly, individuals with high genetic risk and a healthy lifestyle had a 2.65 times higher risk of MCI (95% CI: 2.03 - 3.44).

Additionally, the investigators noted that those with both high genetic risk and an unhealthy lifestyle were found to have the highest risk, at a rate of 3.58 times higher (95% CI: 2.73 - 4.69).

The interaction between genetic risk and lifestyle categories was shown by the team to be synergistic, with a β value of 3.58 (95% CI: 2.73 - 4.69), showing that the combined effect of an unhealthy lifestyle choices and high genetic risk substantially raises the risk of individuals developing MCI.

“Unhealthy lifestyle was associated with a higher risk of MCI among participants with both low and high genetic risk, and lifestyle and genetic risk had synergistic interactions,” they wrote. “These findings could contribute to the development of dietary guidelines and interventions to prevent early-stage dementia.”

References

1. ^{Duan H, Zhou D, Xu N, et al. Association of Unhealthy Lifestyle and Genetic Risk Factors With Mild Cognitive Impairment in Chinese Older Adults. JAMA Netw Open. 2023;6(7):e2324031. doi:10.1001/jamanetworkopen.2023.24031.}
2. ^{Durmaz A, Kumral E, Durmaz B, et al. Genetic factors associated with the predisposition to late onset Alzheimer’s disease. Gene. 2019;707:212-215. doi:10.1016/j.gene.2019.05.030.}