Air Pollution, the Aging Brain and Alzheimer's Disease

空气污染、大脑老化和阿尔茨海默病

• 批准号: 9707467
• 负责人: Gail Li
• 金额: $ 35.54万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9707467
• 关键词: Address; Adult; Adverse effects; Age; Aging; Air Pollutants; Air Pollution; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid beta-Protein; Animals; Antioxidants; Area; Ascorbic Acid; Autopsy; Back; Behavior; Biological Markers; Blood - brain barrier anatomy; Blood Circulation; Brain; Cerebrovascular Disorders; Child; Cognition; Cognitive; Collaborations; Communities; Complex Mixtures; Data; Databases; Dementia; Diagnosis; Disease; Elderly; Enrollment; Environmental Exposure; Environmental Health; Epidemiologist; Exposure to; F2-Isoprostanes; Freezing; Functional disorder; Funding; Gases; Gene-Modified; Genetic; Genotype; Goals; Health; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Impaired cognition; In Vitro; Incidence; Individual; International; Intervention; Lewy Bodies; Lewy Body Disease; Link; Location; Longitudinal prospective study; Measurement; Measures; Medical; Modeling; Molecular; Monitor; National Institute of Environmental Health Sciences; Natural History; Nerve Degeneration; Neurodegenerative Disorders; Nitrogen Oxides; Olfactory Pathways; Outcome; Oxidative Stress; Ozone; Participant; Particulate Matter; Pathologic; Pathology; Persons; Pharmaceutical Preparations; Pharmacy facility; Phenotype; Physicians; Play; Pollution; Population; Positioning Attribute; Prevention; Process; Prospective cohort study; Public Health; Recording of previous events; Records; Regulation; Research; Research Design; Resources; Risk; Risk Factors; Role; Sampling; Science; Scientist; Site; Strategic Planning; Targeted Research; Therapeutic; Time; United States National Institutes of Health; Vitamin E; aging brain; aging population; ambient air pollution; apolipoprotein E-4; base; brain health; cardiovascular health; cerebral atrophy; cerebrovascular; cognitive function; cohort; computerized; data resource; epidemiology study; fine particles; follow-up; fundamental research; genetic variant; healthy aging; improved; insight; misfolded protein; multidisciplinary; neuroinflammation; neuropathology; neurotoxic; neurotoxicity; novel; particle; pollutant; predictive modeling; prospective; public health priorities; residence; respiratory health; response; sound; spatiotemporal; tau Proteins

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.

预防认知能力下降和延迟阿尔茨海默病（AD）的发作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 暴露是普遍的和可改变的，它们是研究大脑健康的适当目标。证据 空气污染与神经退化的联系越来越多，最近的研究表明， 空气污染物（PM2.5）、臭氧（O3）、氮氧化物（NOx和NO2）和交通相关污染的认知水平较低 功能、认知能力下降、AD和全因痴呆的发病率以及脑萎缩。空气的影响 污染物对衰老大脑神经病理学的影响尚不清楚。更深入了解空气污染物， 潜在的风险因素将导致更好地表征疾病机制。改善公共卫生 因为空气污染暴露可以通过法规和个人行为的变化来改变。 很少有流行病学研究能够很好地克服许多固有的弱点， 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 措施，需要提高我们对随时间变化的空气污染暴露的作用的理解， 认知健康、AD和衰老。这项研究是以下领域的领先专家之间的独特合作： 老龄化和AD研究，统计和环境健康科学。它将使用一个长期的前景 队列研究设计，旨在检查空气污染对认知能力下降、全因痴呆和AD的影响 发病率和脑神经病理学。它利用了5,088名成年人的社区样本， 痴呆症在从NIA资助的成人思想变化（ACT）研究登记时。ACT是一个 社区的杰出资源代表，具有前瞻性，长期（长达20年）和高- 高质量的认知随访，按亚型仔细诊断痴呆事件，以及出色的数据可用性 包括633例脑解剖、基因数据以及数十年的广泛医疗和居住历史数据 在研究入组前的几十年内。我们会收集新的空气污染量度方法， ACT参与者对环境PM2.5、O3、NOx和 NO2的最高质量，以解决我们的研究假设。我们的首要目标是识别空气污染风险 因素，并量化其影响，以促进健康老龄化。这项研究提供了一个非凡的 有机会促进我们对空气污染暴露对认知影响的全面理解 和患AD的风险。它与2012-2017年NIEHS战略计划保持一致， 使用最先进的曝光科学进行基础研究。