Cumulative environmental burden and neurodegenerative disease mortality: a national ecological study in the United States

Neurodegenerative diseases (NDDs) represent a growing cause of mortality and disability among aging populations worldwide. However, the relationship between cumulative, multidomain environmental exposures, and NDD mortality remains poorly characterized. This study aimed to examine the association between comprehensive environmental quality and NDD mortality in the United States. We used the environmental quality index (EQI) from 2000 to 2005 to characterize cumulative environmental exposure. Associations between EQI quintiles and NDD mortality, including dementia, Parkinson's disease (PD), amyotrophic lateral sclerosis, and Huntington's disease, were examined using Bayesian interval-censored mixed-effects models. During 2006-2020, among 3.66 million NDD deaths, poorer environmental quality (Q5 vs Q1) was associated with mortality rate differences of 24.72 (95% credible intervals [CrI]: 22.43, 27.06) per 100 000 at 5-year lag, 26.74 (95% CrI: 24.34, 29.21) at 10-year lag, and 22.74 (95% CrI: 20.49, 25.13) at 15-year lag. Within each lag period, a clear dose-response pattern was consistently observed across EQI quintiles. Furthermore, associations were most pronounced for the air quality, followed by sociodemographic disadvantage. In addition, demographic and geographic heterogeneity was observed across sex, race, census regions, urbanicity, climate zone, and county economic type. These findings underscore the need for integrated, place-based environmental health policies targeting neurodegeneration prevention.