ASSOCIATION OF HEALTHY LIFESTYLES AND GENETIC RISK WITH COGNITIVE PERFORMANCE IN OLDER ADULTS
Authors: Chen *Pei-Qi , Wang Shi-Heng 
Published: February 2025

Abstract

Background
The prevalence of dementia among people aged 60 years and older is 7.54%, and the prevalence of mild cognitive impairment is 17.99% in Taiwan [1]. Both genetic risk and lifestyle play a pivotal role in cognitive function [2,3]. However, most previous studies focused on Western populations. There have been neither large-scale studies nor genome-wide risk profiling such as polygenic risk scores (PRS) studies in the Asian populations. It is still unclear whether the effect of healthy lifestyles on cognition varies by genetic risk.

Aims & Objectives
This study aimed to investigate whether healthy lifestyles and PRS for Alzheimer’ s disease (AD-PRS) are associated with cognitive function performance, and to determine whether there is an interaction between healthy lifestyle and AD-PRS on cognitive function performance.

Method
This study uses data from the Taiwan Biobank. In total, 23430 unrelated participants who were aged 60 years and older with Mini-Mental State Examination (MMSE), healthy lifestyles, and genotyping were included in the cross-sectional analyses. Healthy lifestyles include cigarette smoking, alcohol drinking, and physical activity. Among these participants, 6238 had follow-up data and were included in the longitudinal analyses. Cross-sectional associations between AD-PRS, healthy lifestyle, and MMSE at baseline were tested using multivariable linear regression analysis. Associations between AD-PRS, healthy lifestyle, and the changes in MMSE during follow-up were examined using multivariable linear regression analysis. We also tested the interaction between AD-PRS and healthy lifestyles on MMSE and the changes in MMSE.

Results
In the cross-sectional analyses, participants with a high genetic risk (highest quintile) of AD-PRS had worse cognitive function performance compared with participants with a low genetic risk (lowest quintile) (β=-0.09, P-value=0.0441). Compared with the participants who never/seldom drink, the participants who were current drinkers had better cognitive function (β=0.16, P-value=0.0114). In the longitudinal analyses, there was no significant association between AD-PRS and the changes in MMSE. Compared with the participants who never/seldom drink at baseline, the participants who were currently drinking had lower MMSE decline during follow-up (β=-0.29, P-value=0.043). In both the cross-sectional analyses and longitudinal analyses, there was no significant interaction between AD-PRS and healthy lifestyles on cognitive performance.

Discussion & Conclusion
AD-PRS was associated with cognitive performance at baseline. Drinking was associated with better cognitive performance at baseline and lower cognitive decline during follow-up. AD-PRS and healthy lifestyles might impact cognitive function independently.

References
1.About Dementia-Understanding Dementia: TADA-English, [online] http://tada2002.ehosting.com.tw/eng/dementia.html.
2.Baumgart, M., Snyder, H.M., Carrillo, M.C., Fazio, S., Kim, H. & Johns, H. 2015. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective. Alzheimers Dement, 11(6):718-726.
3.Davies, G., et al. 2018. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nat Commun, 9(1):2098.