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)对公众健康有巨大影响，并与 患者、他们的照顾者和整个社会。环境因素在发展中可能是重要的。 以及AD的进展，最近的研究表明，晚年接触空气污染物有助于 老年人的认知表现较差，认知衰退较快。同时， 邻里社会环境(NSE)，特别是邻里社会经济地位和邻里 社会资本被认为与改善认知表现有关，并可能提供对这些影响的适应能力。 这些研究突出了迫切需要检查空气污染物和NSE对AD所在队列的影响 严格和前瞻性地确定、评估潜在关联的途径，并调查标记 敏感度和韧性。银杏记忆评估研究(GEMS)是一项随机试验 旨在评估银杏叶补充剂在降低AD事件风险方面的有效性，并提供 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 暴露有明显的心血管和呼吸影响，但到目前为止，其与阿尔茨海默病的关系 未知。在2000至2008年间，Gemes跟踪了3,000多名年龄在75岁及以上的参与者，他们生活在 针对美国社区的AD，定期进行全面的认知评估，收集 关于包括心血管疾病在内的其他因素的信息，并在人口的一部分中确定 阿尔茨海默病的病理标志--淀粉样蛋白-β的蓄积。详细住宅 GEM参与者可以获得整个随访过程的历史记录，从中我们可以确定 NSE和使用已经开发的最先进的空气模型估计暴露在各种空气污染物中 污染物暴露。我们还将获得在GEMS注册之前长达20年的居住历史， 能够检查空气污染物影响的多个重要暴露窗口 NSE对老年人认知的影响。具体地说，我们建议调查接触空气污染物的影响。 和NSE关于(1)事件AD和认知功能下降，(2)进展到AD和认知轨迹 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，这是确定的 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 空气污染物对阿尔茨海默病风险影响的中介。最后，我们将研究NSE和NSE之间的交互 空气污染以评估AD后果的恢复力或恶化。我们的研究将为我们深入了解 对空气污染物和NSE对大脑的影响很重要，并为旨在预防的战略提供信息， 推迟发病，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.