Associations of perceived neighborhood factors and Alzheimer’s disease polygenic score with cognition: Evidence from the Health and Retirement Study

Background: 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). Methods: 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. Results: 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), cognitive impairment without dementia (HR:1.08; CI:1.03–1.14), and dementia (HR:1.13; CI:1.03–1.24). 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) and cognitive impairment without dementia (HR:1.10; CI:1.05–1.16) but not dementia (HR:1.05; CI:0.96–1.16). No significant interactions were found. Evidence in African ancestries were directionally similar but imprecise and inconclusive due to limited precision and cross-ancestry polygenic score transferability. Subjective neighborhood disadvantage index and Alzheimer’s disease polygenic score were independently associated with incident cognitive impairment. Conclusions: Preventing dementia by addressing modifiable risk factors is essential.