Air Pollution, the Aging Brain and Alzheimer's Disease

空气污染、大脑老化和阿尔茨海默病

基本信息

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
项目类别：
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&apos s Disease Alzheimer&apos 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

项目摘要

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阿尔茨海默氏病（AD）的延迟是公共卫生的重点，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和可修改的，它们是研究大脑健康的合适目标。证据对于空气污染与神经变性的联系正在积累，最近的研究暗示了细颗粒物质（PM2.5），臭氧（O3），氮的氧化物（NOX和NO2）以及较低认知的交通相关污染功能，认知能力下降，AD的发生率和全因痴呆以及脑萎缩。空气的影响衰老大脑中神经病理学的污染物尚不清楚。对空气污染物的更深入理解潜在的危险因素将导致更好地表征疾病机制。改善公共卫生由于空气污染的暴露可以通过法规和个人行为的变化来修改，因此会遵循。很少有流行病学研究被很好地置于克服中的许多固有弱点暴露评估，研究设计和结果数据可用性，包括一组独特的神经病理学措施，需要促进我们对时变空气污染暴露的作用的理解认知健康，广告和衰老。这项研究是领域领域的主要专家的独特合作衰老和广告研究，统计和环境健康科学。它将使用长期前瞻性队列研究设计，以检查空气污染对认知下降，全因痴呆和AD的影响发病率和大脑神经病理学。它利用了5,088名成年人的基于社区的样本 NIA资助的成人思想变化（ACT）研究的入学时痴呆症。行为是一个具有潜在，长期（长达20年）的社区的杰出资源代表，高优质的认知随访，仔细诊断为亚型的事件痴呆以及出色的数据可用性包括633个大脑尸检，遗传数据以及数十年的广泛医学和住宅历史数据在学习入学之前数十年。我们将收集新的空气污染测量以开发 ACT参与者对环境PM2.5，O3，NOX和最高质量的NO 2来解决我们的研究假设。我们的总体目标是确定空气污染风险因素并量化其影响以促进健康的衰老。这项研究提供了非凡的有机会促进我们对空气污染暴露对认知影响的影响的全面理解在衰老的大脑和AD风险中。它通过前进来与2012 - 2017年NIEHS战略计划保持一致使用最先进的暴露科学的基础研究。