Air pollution, the social environment, and Alzheimer's disease: Risk and resilience in the Ginkgo Evaluation Memory Study

摘要 阿尔茨海默病（AD）具有巨大的公共健康影响，并且与治疗阿尔茨海默病的巨大成本相关。 患者，他们的护理人员，以及整个社会。环境因素在发展中可能很重要 最近的研究表明，晚年的空气污染物暴露有助于 老年人的认知能力较低，认知能力下降较快。同时对 邻里社会环境（NSE），特别是邻里社会经济地位和邻里 社会资本与提高认知能力有关，并可能提供对这些影响的恢复力。 这些研究强调了迫切需要检查空气污染物和NSE对AD患者队列的影响。 严格和前瞻性地确定，评估潜在的关联途径，并调查标记物 敏感性和恢复力。银杏记忆力评估研究（GEMS）是一项随机试验， 旨在评估银杏叶补充剂在降低AD发病风险方面的疗效，并提供了一个 非常丰富的临床试验数据资源，用于研究NSE和空气污染，环境 暴露具有已证实的心血管和呼吸影响，但其与AD的关系，截至目前， 未知在2000年至2008年期间，GEMS跟踪了3,000多名年龄在75岁及以上的参与者，他们居住在四个城市， 社区在美国的AD，定期进行全面的认知评估，收集 关于其他因素的信息，包括心血管疾病，并在一个子集的人口，确定 使用PET脑成像的AD的病理标志淀粉样蛋白-β的积累。详细住宅 GEMS参与者可获得整个随访过程中的病史，从中我们可以确定 NSE和估计暴露于各种空气污染物使用已经开发的国家的最先进的空气模型 污染物暴露。我们还将获得在GEMS注册前20年的居住历史， 能够检查在空气污染物的影响中具有重要意义的多个暴露窗口， NSE对老年人认知的影响具体而言，我们建议调查空气污染物暴露的影响 和NSE对（1）AD事件和认知下降，（2）AD进展和认知轨迹， 在研究开始时有轻度认知障碍的参与者，以及（3）淀粉样蛋白-β沉积， 在GEM研究参与者的子集中。我们将调查心血管疾病和抑郁症作为潜在的 空气污染物对AD风险影响的介体。最后，我们将研究NSE和 空气污染，以评估AD结果的恢复力或恶化。我们的研究将提供深入了解途径 重要的空气污染物和神经元特异性烯醇化酶对大脑的影响，并告知旨在预防， 延迟发病，减缓影响数百万美国人的毁灭性疾病的进展。

ABSTRACT Alzheimer’s disease (AD) has tremendous public health impacts and is associated with enormous costs to patients, their caregivers, and society as a whole. Environmental factors may be important in the development and progression of AD with recent research demonstrating that air pollutant exposure late in life contributes to lower cognitive performance and faster cognitive decline in older populations. At the same time, the neighborhood social environment (NSE), specifically neighborhood socioeconomic status and neighborhood social capital, has been linked to improved cognitive performance and may provide resilience to these effects. These studies highlight an urgent need to examine air pollutant and NSE impacts in cohorts in which AD is rigorously and prospectively ascertained, evaluate pathways underlying associations, and investigate markers of susceptibility and resilience. The Ginkgo Evaluation of Memory Study (GEMS) was a randomized trial designed to evaluate the efficacy of Ginkgo biloba supplements in lowering risk of incident AD and provides an extraordinarily rich resource of clinical trial data for a study of the NSE and air pollution, an environmental exposure with demonstrated cardiovascular and respiratory effects but whose relationship with AD is, as of yet, unknown. Between 2000 and 2008, GEMS followed over 3,000 participants aged 75 and older living in four communities in the United States for AD, regularly conducted comprehensive cognitive assessments, collected information on other factors including cardiovascular disease and, in a subset of the population, ascertained accumulation of amyloid-β, the pathological hallmark of AD, using PET brain imaging. Detailed residential histories throughout follow-up are available for GEMS participants from which we can ascertain measures of the NSE and estimate exposure to various air pollutants using already developed state-of-the art models of air pollutant exposure. We also will obtain residential histories up to 20 years prior to enrollment in GEMS, enabling the examination of multiple exposure windows of importance in the effects of air pollutants and the NSE on cognition in older adults. Specifically, we propose to investigate the impact of air pollutant exposures and the NSE on (1) incident AD and cognitive decline, (2) the progression to AD and cognitive trajectories in participants with mild cognitive impairment at study entry, and (3) amyloid-β deposition, which was ascertained in a subset of GEM study participants. We will investigate cardiovascular disease and depression as potential mediators of the effects of air pollutants on AD risk. Finally we will examine the interaction between NSEs and air pollution to assess resilience or exacerbation of AD outcomes. Our study will provide insight into pathways important in the effects of air pollutants and the NSE on the brain and inform strategies aimed at preventing, delaying the onset, and slowing the progression of a devastating disease affecting millions of Americans.