The association of Alzheimer's disease genetic risk with social connectedness in middle- and older ages.

Observational evidence suggests that social connectedness protects against Alzheimer's disease (AD), but reverse causality has not been ruled out. We evaluated the potential for a reverse path by estimating associations between AD genetic risk score (AD-GRS) and social connectedness across mid and late-life. We used data from 487 194 UK Biobank participants aged 40+ years and considered social connectedness measures capturing social isolation, loneliness, relationship satisfaction, emotional support, and diverse social activity participation. Participants' mean age was 56.5 (SD: 8.2) years. Higher AD-GRS was associated with a lower social isolation score (β = 0.01; 95% CI, -0.014 to -0.001); these associations strengthened with age. Higher AD-GRS was associated with higher levels of family relationship satisfaction (β = 0.01; 95% CI, 0.001-0.01), but this association was attenuated with age. Higher AD-GRS was associated with engaging in a wider variety of social activities (β = 0.02, 95% CI, 0.004-0.03), with no evidence of heterogeneity by age. Associations with loneliness, friendship relationship quality, and perceived emotional support were null. Overall, we did not find evidence that higher risk of AD is associated with reduced social connectedness. Instead, preclinical AD symptoms may lead to stronger family relationships and lower social isolation.