Air Pollution, the Aging Brain and Alzheimer's Disease

预防认知衰退和延缓阿尔茨海默病(AD)的发病是公共卫生的优先事项， 改善大脑健康是美国国立卫生研究院的坚定承诺。由于环境空气污染 暴露是普遍的和可修改的，它们是研究大脑健康的合适目标。证据 因为空气污染与神经退化的联系正在积累，最近的研究表明，细颗粒物 物质(PM2.5)、臭氧(O3)、氮氧化物(NOx和NO2)和与交通相关的污染 功能、认知能力下降、阿尔茨海默病和全因痴呆症的发生率，以及脑萎缩。空气的影响 污染物对衰老大脑中神经病理的影响尚不清楚。加深对空气污染物的理解 潜在的风险因素将导致更好地描述疾病机制。改善公共卫生状况 由于空气污染暴露可以通过法规和个人行为的变化而改变，因此将随之而来。 很少有流行病学研究能够很好地克服艾滋病的许多固有弱点 暴露评估、研究设计和结果数据可用性，包括一套独特的神经病理学 所需的措施，以促进我们对时变空气污染暴露在 认知健康、阿尔茨海默病和衰老。这项研究是在以下领域的领先专家之间的独特合作 老龄化和AD研究、统计学和环境健康科学。它将使用一个长期的前瞻性 研究空气污染对认知功能减退、全因痴呆症和阿尔茨海默病影响的队列研究设计 发病率和脑神经病理学。它利用了5088名成年人的社区样本，免费 NIA资助的成人思维变化(ACT)研究登记时的痴呆症。行为是一种 优秀的社区资源代表，具有前瞻性、长期性(长达20年)和高- 高质量的认知跟踪，按子类型仔细诊断偶发痴呆症，以及出色的数据可用性 包括633例脑部尸检、基因数据，以及数十年的广泛医疗和居住史数据 在入学前延长了几十年。我们将收集新的空气污染测量数据，以供开发 ACT参与者对环境PM2.5、O3、NOx和 最高质量的2号，以解决我们的研究假设。我们的首要目标是确定空气污染风险。 并量化其影响因素，以促进健康老龄化。这项研究提供了一种非同寻常的 促进我们对空气污染暴露对认知的影响的全面了解的机会 在老化的大脑和阿尔茨海默病的风险上。它与2012-2017年NIEHS战略计划很好地保持一致，通过推进 使用最先进的曝光科学进行基础研究。

Prevention of cognitive decline and delay of onset of Alzheimer's disease (AD) are public health priorities, and improving brain health is a firm commitment of the National Institutes of Health. Since ambient air pollution exposures are pervasive and modifiable, they are an appropriate target for research on brain health. Evidence for air pollution links to neurodegeneration is accumulating with recent studies implicating fine particulate matter (PM2.5), ozone (O3), oxides of nitrogen (NOx and NO2) and traffic-related pollution in lower cognitive function, cognitive decline, incidence of AD and all-cause dementia, and brain atrophy. The effects of air pollutants on neuropathology in the aging brain are unknown. Deeper understanding of air pollutants as potential risk factors will lead to better characterization of disease mechanisms. Improvements in public health will follow since air pollution exposures can be modified by changes in regulations and individual behaviors. Few epidemiological studies have been well-positioned to overcome many of the inherent weaknesses in exposure assessment, study design, and outcome data availability, including a unique set of neuropathology measures, needed to advance our understanding of the role of time-varying air pollution exposures on cognitive health, AD, and aging. This study is a unique collaboration between leading experts in the fields of aging and AD research, statistical, and environmental health sciences. It will use a long-term prospective cohort study design to examine the effects of air pollution on cognitive decline, all-cause dementia and AD incidence, and brain neuropathologies. It leverages the community-based sample of 5,088 adults free of dementia at the time of enrollment from the NIA-funded Adult Changes in Thought (ACT) study. ACT is an outstanding resource representative of the community with prospective, long-term (up to 20 years), and high- quality cognitive follow-up, careful diagnosis of incident dementia by subtype, and outstanding data availability including 633 brain autopsies, genetic data, and decades of extensive medical, and residential history data extending decades prior to study enrollment. We will collect new air pollution measurements to develop for ACT participants state-of-the-art long-term average air pollution predictions for ambient PM2.5, O3, NOx, and NO2 of the highest quality to address our study hypotheses. Our overarching goal is to identify air pollution risk factors and quantify their effects in order to promote healthy aging. This study provides an extraordinary opportunity to advance our comprehensive understanding of the effects of air pollution exposures on cognition in the aging brain and on risk of AD. It aligns well with the 2012-2017 NIEHS Strategic Plan by advancing fundamental research using state-of-the-art exposure science.