Associations of Perceived Neighborhood Factors and Alzheimer's Disease Polygenic Score with Cognition: Evidence from the Health and Retirement Study.

We examined the relationships between neighborhood characteristics, cumulative genetic risk for Alzheimer's disease (polygenic scores for Alzheimer's disease), and cognitive function using data from the Health and Retirement Study (2008-2020, age>50). Baseline perceived neighborhood characteristics were combined into a subjective neighborhood disadvantage index. Cognitive function was assessed at baseline and measured biennially over a 10-year follow-up period. Analyses were stratified by genetic ancestry. Cox proportional hazard models analyzed associations between neighborhood characteristics, Alzheimer's disease polygenic scores, and their interactions on cognitive impairment. In the European ancestries sample, a one standard deviation higher score on the subjective neighborhood disadvantage index was associated with a higher hazard of any cognitive impairment (HR:1.09; CI:1.03-1.15). Similarly, a one standard deviation increase in Alzheimer's disease polygenic score was associated with a higher risk of cognitive impairment (HR:1.10; CI:1.05-1.16). Similar effect sizes were observed when examining cognitive impairment without dementia and dementia separately. No significant interactions were found. Comparable but nonsignificant trends were noted in the African ancestries sample. Subjective neighborhood disadvantage index and Alzheimer's disease polygenic score were independently associated with incident cognitive impairment. Preventing dementia by addressing modifiable risk factors is essential.