Ware Erin B, Zhu Peiyao, Noppert Grace, Fu Mingzhou, Benbow Mikayla, Kobayashi Lindsay C, Ryan Lindsay H, Bakulski Kelly M
Survey Research Center, Institute for Social Research Center, University of Michigan, 426 Thompson St, Ann Arbor, MI, 48104, USA.
Population Studies Center, Institute for Social Research Center, University of Michigan, 426 Thompson St, Ann Arbor, MI, 48104, USA.
medRxiv. 2025 Mar 15:2025.03.14.25324002. doi: 10.1101/2025.03.14.25324002.
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.
我们利用健康与退休研究（2008 - 2020年，年龄>50岁）的数据，研究了社区特征、阿尔茨海默病的累积遗传风险（阿尔茨海默病的多基因评分）与认知功能之间的关系。将基线时感知到的社区特征合并为一个主观社区劣势指数。在基线时评估认知功能，并在10年的随访期内每两年测量一次。分析按遗传血统分层。Cox比例风险模型分析了社区特征、阿尔茨海默病多基因评分及其对认知障碍的相互作用之间的关联。在欧洲血统样本中，主观社区劣势指数上一个标准差更高的分数与任何认知障碍的更高风险相关（风险比：1.09；可信区间：1.03 - 1.15）。同样，阿尔茨海默病多基因评分增加一个标准差与认知障碍的更高风险相关（风险比：1.10；可信区间：1.05 - 1.16）。在分别检查无痴呆的认知障碍和痴呆时，观察到了类似的效应大小。未发现显著的相互作用。在非洲血统样本中注意到了类似但不显著的趋势。主观社区劣势指数和阿尔茨海默病多基因评分与新发认知障碍独立相关。通过解决可改变的风险因素来预防痴呆至关重要。
