Exposure to Multiple Fine Particulate Matter Components and Incident Depression in the US Medicare Population

Importance: Growing evidence suggests that long-term exposure to fine particulate matter (PM2.5) is associated with an increased risk of depression. However, the contributions of specific PM2.5 components and the modifying roles of comorbidities remain unclear. Objective: To evaluate the individual and joint associations of long-term exposure to PM2.5 and its major components with incident depression, and to assess whether comorbidities modify these associations. Design, Setting, and Participants: This nationwide, population-based cohort study used Medicare data from January 2000 to December 2018. Medicare beneficiaries aged 65 years or older who were continuously enrolled in the fee-for-service component of Medicare only, resided in the contiguous US during the study period, and had both Part A and Part B were included. Data were analyzed from November 2023 to October 2025. Exposures: Annual concentrations of PM2.5 mass and its major components, including elemental carbon, ammonium, nitrate, sulfate, soil dust (largely silicon), and organic carbon, were assessed using a spatiotemporal model. Main Outcomes and Measures: Late-life depression diagnoses were identified by Medicare claims. Cox proportional hazard models and quantile g-computation (QGC) were applied to estimate the individual and joint associations of PM2.5 and its major components with depression risk. Stratified analyses by various comorbidities were also applied to evaluate the potential effect size modifiers. Results: Among 23 696 223 older adults (mean SD age at entry, 76.0 6.4 years; 13 081 668 female 55.2%), 5 544 678 developed depression during follow-up. In single-pollutant models, PM2.5 mass (hazard ratio HR, 1.02; 95% CI, 1.01-1.02) and 4 of 6 major components (sulfate: HR, 1.05; 95% CI, 1.04-1.06; elemental carbon: HR, 1.03; 95% CI, 1.03-1.04; soil dust: HR, 1.03; 95% CI, 1.03-1.04; and ammonium: HR, 1.01; 95% CI, 1.01-1.02) were positively associated with depression. A mixture of multiple PM2.5 major components had a much larger association with depression than PM2.5 mass itself, with each 1-quartile increase in the mixture being associated with increased depression risk (HR, 1.07; 95% CI, 1.06-1.07). The QGC further identified soil dust (weight = 0.41), sulfate (weight = 0.34), and elemental carbon (weight = 0.25) as the main contributors. Associations were more pronounced among individuals with cardiometabolic and neurologic comorbidities. Conclusions and Relevance: In this cohort study of the US Medicare population, specific PM2.5 components (sulfate, elemental carbon, and soil dust) were associated with increased depression risk in older adults, particularly those with preexisting comorbidities. These findings underscore the importance of targeted regulation of harmful PM2.5 components to protect vulnerable populations.