Polygenic Score for Alzheimer Disease and cognition: The mediating role of personality.

Alzheimer's disease (AD) polygenic risk score (PGS) is associated with lower cognitive functioning even among older individuals without dementia. We tested the hypothesis that personality traits mediate the association between AD genetic risk and cognitive functioning. Participants (N > 7,000, aged 50-99 years old) from the Health and Retirement Study were genotyped and completed personality and cognition tests at baseline. Cognition was assessed again four years later. Bootstrap analysis revealed that a higher AD polygenic risk score was associated with lower cognitive scores at baseline through higher neuroticism, lower conscientiousness, and lower levels of the industriousness facet of conscientiousness. In addition, a higher polygenic score for AD was associated with decline in cognition over four years in part through higher neuroticism and lower conscientiousness. The findings support the hypothesis that the genetic vulnerability for AD contributes to cognitive functioning in part through its association with personality traits.