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

## TL;DR

This study explores how neighborhood factors and genetic risk for Alzheimer's disease relate to cognitive function in older adults.

## Contribution

The study shows that neighborhood disadvantage and Alzheimer’s disease polygenic scores independently predict cognitive impairment.

## Key findings

- Higher neighborhood disadvantage was linked to increased risk of cognitive impairment in European ancestry groups.
- Alzheimer’s disease polygenic scores were associated with higher risk of cognitive impairment but not dementia.
- Findings in African ancestry groups were less precise due to genetic score limitations.

## Abstract

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), 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.

Preventing dementia by addressing modifiable risk factors is essential.