Effects of Traffic-Related Air Pollution on Cognitive Function, Dementia Risk, an

描述（由申请人提供）：长期暴露于空气污染，特别是与交通有关的空气污染，与心血管发病率和死亡率有关。关于这些暴露对神经退行性疾病的影响知之甚少。有证据表明，全身性炎症反应，大脑是特别脆弱的，可能介导心血管效应，这表明神经退行性疾病也可能受到这种环境损伤。虽然其他研究已经表明潜在的血管病变和神经退行性变之间的关联，但到目前为止，空气污染对大脑的影响已经以有限的方式研究。我们建议在心血管健康研究（CHS）中调查空气污染暴露，认知能力下降和痴呆风险以及MRI检测到的大脑异常之间的关联，CHS是一项大型的NHLBI资助的老年人冠心病和中风纵向研究。该建议利用了CHS中脑MRI和认知评估的独特的基于人群的表型资源。与现有的CHS空气污染和心血管疾病风险的辅助研究合作，我们将扩大对车辆排放产生的空气污染物暴露的估计，以评估空气污染和神经系统结果之间的关系。结果将包括认知能力、流行和偶发痴呆（阿尔茨海默病和血管性痴呆）、MRI检测到的脑异常（包括脑梗死和白色疾病）的存在，以及这些指标随时间的变化。利用研究人员在认知功能和痴呆症，大脑MRI结果以及空气污染对健康影响方面的专业知识，拟议的项目提供了一个独特的机会来研究空气污染对大脑的影响。 公共卫生相关性：老年人认知能力下降和痴呆的患病率极高。研究表明，环境因素可能在疾病的发展中发挥作用;然而，很少有工作研究空气污染，特别是与交通有关的空气污染物对神经退行性疾病的潜在贡献。这项研究将结合联合收割机研究人员在暴露建模方面的专业知识和独特丰富的纵向测量神经学结果数据库，以研究空气污染对大型，地理上不同的老年人人群大脑的影响。鉴于空气污染暴露的普遍性，其与心血管发病率和死亡率的联系以及潜在血管疾病与认知能力下降和痴呆之间的公认联系，这项研究具有非常重要的意义。

DESCRIPTION (provided by applicant): Long-term exposure to air pollution, particularly traffic-related air pollution, is associated with cardiovascular morbidity and mortality. Less is known about the impact of these exposures on neurodegenerative disorders. Evidence suggests that systemic inflammation, a response to which the brain is particularly vulnerable, may mediate cardiovascular effects, suggesting that neurodegenerative disorders may also be subject to this environmental injury. Although other studies have shown associations between underlying vascular pathology and neurodegeneration, the effects of air pollution on the brain have been studied in a limited manner thus far. We propose to investigate associations between air pollution exposure, cognitive decline and risk of dementia, and MRI-detected brain abnormalities in the Cardiovascular Health Study (CHS), a large, NHLBI-funded longitudinal study of coronary heart disease and stroke in older adults. This proposal takes advantage of the unique population-based phenotypic resource of brain MRI and cognitive assessment in CHS. In collaboration with an existing CHS ancillary study on air pollution and risk of cardiovascular disease, we will expand upon estimates of exposure to air pollutants produced by vehicle emissions to evaluate the relationship between air pollution and neurological outcomes. Outcomes will include cognitive performance, prevalent and incident dementia (both Alzheimer's disease and vascular dementia), presence of MRI-detected brain abnormalities including brain infarcts and white matter disease, and changes in these measures over time. Drawing on investigator expertise in cognitive function and dementia, brain MRI findings, and the health effects of air pollution, the proposed project provides a unique opportunity to examine air pollution effects on the brain. PUBLIC HEALTH RELEVANCE: The prevalence of cognitive decline and dementia in the elderly is extremely high. Research suggests that environmental factors may play a role in the development of disease; however, little work has examined the potential contribution of air pollution, and particularly traffic-related air pollutants, to neurodegeneration. This study will combine investigator expertise in exposure modeling with a uniquely rich database of longitudinally measured neurological outcomes, to examine the effects of air pollution on the brain in a large, geographically diverse population of older adults. This research is highly significant in light of the pervasiveness of air pollution exposure, its demonstrated links to cardiovascular morbidity and mortality, and the recognized associations between underlying vascular disease and cognitive decline and dementia.