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。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（大脑特别容易受到的一种反应）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的影响。尽管其他研究表明潜在的血管病理学和神经退行性变之间存在关联，但迄今为止，空气污染对大脑的影响的研究还很有限。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、痴呆风险和mri检测到的大脑异常之间的关系，这是一项由nhlbi资助的大型老年人冠心病和中风纵向研究。该建议利用了独特的基于人群的脑MRI和认知评估的表型资源。我们将与现有的CHS关于空气污染和心血管疾病风险的辅助研究合作，扩大对车辆排放产生的空气污染物暴露的估计，以评估空气污染与神经系统结果之间的关系。结果将包括认知表现、普遍和偶然的痴呆（阿尔茨海默病和血管性痴呆）、mri检测到的脑异常（包括脑梗死和白质疾病）的存在，以及这些指标随时间的变化。利用研究者在认知功能和痴呆症、大脑MRI发现和空气污染对健康影响方面的专业知识，拟议的项目为研究空气污染对大脑的影响提供了一个独特的机会。

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.