Keller Sarah A, DeWitt Amanda, Powell W Ryan, Ketchum Frederick B, Rissman Robert A, Bendlin Barbara B, Kind Amy J H
Center for Health Disparities Research, University of Wisconsin School of Medicine and Public Health, Madison.
Department of Medicine, Geriatrics Division, University of Wisconsin School of Medicine and Public Health, Madison.
JAMA Netw Open. 2025 May 1;8(5):e2512289. doi: 10.1001/jamanetworkopen.2025.12289.
The adverse social exposome, the entirety of harmful lifetime social-environmental exposures, is associated with Alzheimer disease and related dementias (ADRD) risk and may be key to informing modifiable systemic and behavioral risk interventions. With increasing emphasis to understand lifetime risk, methods are needed to measure and study social exposome relative to ADRD-related biological processes, including cerebrovascular disease.
To evaluate the association between adverse social exposome and the burden of vascular brain injury (VBI) post mortem.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study analyzed brain bank donors from 2 Alzheimer Disease Research Centers. Donations occurred between January 5, 2000, and August 5, 2018. Analysis was performed between January 13 and July 20, 2023.
Adverse social exposome, via geo-linked, time-concordant Area Deprivation Index (ADI) rankings for each year of a donor's lifetime.
The main outcome consisted of the presence or absence of VBI indicators: infarcts, microinfarcts, hemorrhages, and white matter rarefaction. Association between cumulative or change in life-course ADI and VBI burden was evaluated using multivariate logistic regression models adjusted for sex and age at death.
The sample included 740 donors (417 female [56.4%]; mean [SD] age at death, 81.5 [10.3] years; mean [SD] VBI score, 0.7 [1.0]; and median life course ADI, 7.08 [IQR, 4.33-9.83]), with residential years spanning 1905 to 2018. In adjusted models, living more years in a county with an ADI ranked above the study population median was associated with increased VBI odds (adjusted odds ratio [AOR], 1.04; 95% CI, 1.03-1.05). Greater odds of VBI were identified in those with increasing ADI between youth and adulthood (AOR, 3.67; 95% CI, 3.65-3.70) and youth and older adulthood (AOR, 12.02; 95% CI, 7.87-18.35). Increased odds were found in groups with stable high median ADI from youth to adulthood (AOR, 3.08; 95% CI, 3.01-3.14) and youth to older adulthood (AOR, 8.46; 95% CI, 8.04-8.90).
In this cohort study of 740 brain bank donors, an association between ADI and the presence of VBI was indicated, when considering the full life course as well as specific life course periods. These results show promise for identifying geographic areas in need of targeted interventions to reduce cerebrovascular disease and ADRD risk factors.
不良社会暴露组，即一生中所有有害的社会环境暴露的总和，与阿尔茨海默病及相关痴呆症（ADRD）风险相关，可能是为可改变的系统性和行为风险干预措施提供信息的关键。随着对理解终生风险的重视日益增加，需要有方法来测量和研究与ADRD相关生物过程（包括脑血管疾病）相关的社会暴露组。
评估不良社会暴露组与死后血管性脑损伤（VBI）负担之间的关联。
设计、设置和参与者：这项回顾性队列研究分析了来自2个阿尔茨海默病研究中心的脑库捐赠者。捐赠时间为2000年1月5日至2018年8月5日。分析于2023年1月13日至7月20日进行。
通过与地理位置相关、时间一致的捐赠者一生中每年的区域剥夺指数（ADI）排名来衡量不良社会暴露组。
主要结局包括是否存在VBI指标：梗死、微梗死、出血和白质稀疏。使用根据死亡时的性别和年龄进行调整的多变量逻辑回归模型，评估生命历程中累积或变化的ADI与VBI负担之间的关联。
样本包括740名捐赠者（417名女性[56.4%]；死亡时的平均[标准差]年龄为81.5[10.3]岁；平均[标准差]VBI评分为0.7[1.0]；生命历程ADI中位数为7.08[四分位间距，4.33 - 9.83]），居住年限跨度为1905年至2018年。在调整后的模型中，在ADI排名高于研究人群中位数的县居住时间更长与VBI几率增加相关（调整后的比值比[AOR]，1.04；95%置信区间，1.03 - 1.05）。在青年到成年期（AOR，3.67；95%置信区间，3.65 - 3.70）以及青年到老年期（AOR，12.02；95%置信区间，7.87 - 18.35）ADI增加的人群中，VBI几率更高。在从青年到成年期（AOR，3.08；95%置信区间，3.01 - 3.14）以及青年到老年期（AOR，8.46；95%置信区间，8.04 - 8.90）中位数ADI持续较高的人群中，几率也增加。
在这项对740名脑库捐赠者的队列研究中，考虑整个生命历程以及特定生命历程阶段时，表明ADI与VBI的存在之间存在关联。这些结果有望用于识别需要针对性干预以降低脑血管疾病和ADRD风险因素的地理区域。
