Social Isolation, Social Interaction, and Alzheimer’s Disease: A Mendelian Randomization Study

Social isolation and social interaction have been suggested to be associated with Alzheimer's disease. However, the causality cannot be unambiguously assessed as traditional epidemiological methods are easily subject to unmeasured confounders and potential bias.To examine bidirectional relationships between social isolation, social interaction, and Alzheimer's disease using Mendelian randomization method for assessing potential causal inference.This bidirectional two-sample Mendelian randomization study used independent genetic variants associated with social isolation and social interaction (n = 302,567-487,647), and Alzheimer's disease (n = 455,258). MR analyses were performed using the inverse-variance-weighted (IVW) as the main MR analytical method to estimate the causal effect. For sensitivity analyses, we applied weighted median, MR Egger to further assess the credibility of the causal effect.Of the five types of social engagement examined in our study, only one showed evidence of an association with the risk of Alzheimer's disease. Attendance at a gym or sports club (IVW OR per SD change: 0.670; 95% CI: 0.463-0.970; p = 0.034) was inversely associated with the risk of Alzheimer's disease. We also found that AD may reduce the attendance at religious group (IVW OR per SD change: 1.017; 95% CI: 1.005-1.030; p = 0.004).This study suggests that regular attendance at a gym or sports club is causally associated with reduced risk of Alzheimer's disease. Further studies are warranted to elucidate potential mechanisms.