PROJECT ABSTRACT Burgeoning evidence suggests that exposure to air pollution may result in impaired cognitive function, cognitive decline, and increased risk of Alzheimer's disease and related dementias (ADRD). Newer, sparser evidence hints that these outcomes could also be influenced by ambient noise. If these environmental exposures do worsen cognition in older adults, they would be among the few pervasive risk factors for cognitive loss that can be modified on broad scale to benefit entire populations. Despite major implications for public health, there are critical limitations in our knowledge of how air pollution and noise affect neurocognitive aging. Most studies of these exposures in relation to ADRD have relied on medical or health administrative records, which provide strikingly unreliable data on dementia status. Both exposures increase cardiovascular risk. If health care use for these conditions makes it more likely that a person with dementia is diagnosed, then using medical records to estimate of the relation of air pollution and noise to ADRD risk could overestimate these associations. A second limitation is that the mechanisms by which these exposures promote cognitive deterioration are unclear, although cerebrovascular pathways have been proposed. Finally, air pollution and ambient noise often co-occur, yet few studies have been able to determine if these exposures amplify each other's effects. To overcome these limitations and knowledge gaps, we propose to investigate the effects of air pollution and noise exposure on cognitive decline and ADRD and, using brain MRI measurements, to evaluate these exposures' influence on cerebrovascular injury and neuronal death. We take advantage of 2 large, racially diverse population-based cohort studies of older adults, the Chicago Health and Aging Project (CHAP) and the Parent Offspring Resilience and Cognitive Health (PORCH) study. We will integrate data from cohort participants on cognitive decline, ADRD, and brain MRI with estimates of their long-term exposures to noise and air pollution from traffic, generated in ongoing collaboration with the MESA Air and ancillary projects. We will focus on traffic-related air pollution (TRAP), because traffic remains one of the most pervasive sources of air pollution exposure. This work extends our ongoing research by: investigating brain MRI measures of cerebrovascular injury; evaluating other constituents of TRAP, including the metals released from brake and tire wear; and evaluating the effects of TRAP and noise in combination. Our overarching hypothesis is that TRAP and noise exposures hasten cognitive decline, increase ADRD risk, and promote cerebrovascular ischemia and brain atrophy. We further hypothesize that TRAP and noise exposure together influence these outcomes, above and beyond what would be expected from their individual associations with these outcomes. Reductions in environmental pollutants have already benefited the population's health. The data from this project may provide impetus—the prospect of reducing the population burden of ADRD—for further reductions and identify both air pollution and noise as targets for population-level strategies for ADRD prevention.

PROJECT NARRATIVE The proposed project will investigate two environmental toxicants as risk factors for Alzheimer's disease and related causes of dementia (ADRD): air pollution and community noise. Much of the population is exposed to high levels of both pollutants, and if they contribute to the development of ADRD, regulations and technological innovations could be used to reduce exposures and shift the population's risk of ADRD downward. This project will advance our understanding of air pollution, noise and ADRD by: studying the subclinical effects of both exposures on cerebrovascular disease, in addition to dementia and cognitive decline; homing in on pollutants from motor vehicle traffic, a major source of air pollution exposure; and applying analytical methods to adjust for common problems in ADRD research.