Challenges in studying air pollution to neurodegenerative diseases

Exposure to ambient air pollution is ubiquitous and unavoidable. While associations between air pollution and cardiometabolic diseases are well-established, its role in neurodegenerative diseases, such as Alzheimer's disease and related dementias (ADRD) and Parkinson's disease (PD), has only recently begun to emerge. This narrative review provides an overview of current findings and discusses challenges and opportunities for future epidemiologic research. Mechanistically, air pollution may contribute to ADRD and PD through neuroinflammation, oxidative stress, and cerebrovascular damage. Long-term exposure to high levels of air pollution may increase the risk of ADRD and PD. Over the past 20 years, more than 50 studies have examined air pollution and ADRD, while fewer studies have focused on PD. Although the estimated effects are modest in size, they translate into a substantial number of affected individuals due to the widespread nature of the exposure and an increasingly aging population worldwide. Future research should extend exposure periods to cover younger and middle ages, estimate the effects of long-term cumulative exposures, and evaluate moderators and mediators, such as diet, physical activity, green space, and noise. More studies are also needed to include large and diverse populations, including those with special vulnerabilities and emerging exposures like wildfire smoke.