Shaffer Rachel M, Li Ge, Adar Sara D, Dirk Keene C, Latimer Caitlin S, Crane Paul K, Larson Eric B, Kaufman Joel D, Carone Marco, Sheppard Lianne
Department of Environmental and Occupational Health Sciences, University of Washington School of Public Health, Seattle, WA, USA.
VA Northwest Network Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.
J Alzheimers Dis. 2021;79(4):1761-1773. doi: 10.3233/JAD-201005.
Evidence links fine particulate matter (PM2.5) to Alzheimer's disease (AD), but no community-based prospective cohort studies in older adults have evaluated the association between long-term exposure to PM2.5 and markers of AD neuropathology at autopsy.
Using a well-established autopsy cohort and new spatiotemporal predictions of air pollution, we evaluated associations of 10-year PM2.5 exposure prior to death with Braak stage, Consortium to Establish a Registry for AD (CERAD) score, and combined AD neuropathologic change (ABC score).
We used autopsy specimens (N = 832) from the Adult Changes in Thought (ACT) study, with enrollment ongoing since 1994. We assigned long-term exposure at residential address based on two-week average concentrations from a newly developed spatiotemporal model. To account for potential selection bias, we conducted inverse probability weighting. Adjusting for covariates with tiered models, we performed ordinal regression for Braak and CERAD and logistic regression for dichotomized ABC score.
10-year average (SD) PM2.5 from death across the autopsy cohort was 8.2 (1.9) μg/m3. Average age (SD) at death was 89 (7) years. Each 1μg/m3 increase in 10-year average PM2.5 prior to death was associated with a suggestive increase in the odds of worse neuropathology as indicated by CERAD score (OR: 1.35 (0.90, 1.90)) but a suggestive decreased odds of neuropathology as defined by the ABC score (OR: 0.79 (0.49, 1.19)). There was no association with Braak stage (OR: 0.99 (0.64, 1.47)).
We report inconclusive associations between PM2.5 and AD neuropathology at autopsy among a cohort where 94% of individuals experienced 10-year exposures below the current EPA standard. Prior studies of AD risk factors and AD neuropathology are similarly inconclusive, suggesting alternative mechanistic pathways for disease or residual confounding.
有证据表明细颗粒物（PM2.5）与阿尔茨海默病（AD）有关，但尚无针对老年人的基于社区的前瞻性队列研究评估长期暴露于PM2.5与尸检时AD神经病理学标志物之间的关联。
利用一个成熟的尸检队列和新的空气污染时空预测，我们评估了死亡前10年PM2.5暴露与Braak分期、阿尔茨海默病注册协会（CERAD）评分以及联合AD神经病理改变（ABC评分）之间的关联。
我们使用了自1994年以来一直在进行入组的“成人思维变化”（ACT）研究中的尸检标本（N = 832）。我们根据一个新开发的时空模型中的两周平均浓度来确定居住地址的长期暴露情况。为了考虑潜在的选择偏倚，我们进行了逆概率加权。通过分层模型调整协变量后，我们对Braak和CERAD进行了有序回归，对二分的ABC评分进行了逻辑回归。
整个尸检队列中死亡前10年的平均（标准差）PM2.5为8.2（1.9）μg/m3。死亡时的平均年龄（标准差）为89（7）岁。死亡前10年平均PM2.5每增加1μg/m3，与CERAD评分所表明的神经病理学恶化几率的提示性增加相关（比值比：1.35（0.90，1.90）），但与ABC评分所定义的神经病理学几率的提示性降低相关（比值比：0.79（0.49，1.19））。与Braak分期无关联（比值比：0.99（0.64，1.47））。
在一个94%的个体10年暴露低于当前美国环境保护局标准的队列中，我们报告了尸检时PM2.5与AD神经病理学之间的关联尚无定论。先前关于AD危险因素和AD神经病理学的研究同样尚无定论，这表明存在疾病的替代机制途径或残留混杂因素。
