Association of cumulative metal exposure with multidimensional cognitive and systemic inflammatory profiles in older adults

Environmental exposure to metals has been linked to cognitive decline; however, the impact of cumulative exposure to metal mixtures on cognitive function in older adults remains insufficiently understood. We studied 349 older adults in 2021 and 2024, measuring cumulative metal exposure using blood samples. In 2024, cognitive function was comprehensively assessed using the Montreal Cognitive Assessment scale in conjunction with six blood-based markers associated with cognition. Systemic inflammation was evaluated through the calculation of two inflammatory indices derived from complete blood count data, as well as the measurement of two key inflammatory cytokines in plasma. Associations between exposure and outcomes were analyzed using multiple linear regression, quantile-based G-computation, and Bayesian kernel machine regression models, with inflammation’s mediating role examined. Cumulative exposure to metal mixtures was significantly linked to cognitive decline, especially attention deficits associated with copper and lead (Pb), and altered amyloid markers tied to Pb. Inflammatory indices were inversely related to cumulative exposure to metal mixtures, primarily due to iron and selenium. Inflammation did not mediate these associations. Our findings indicate that cumulative exposure to metal mixtures is associated with detrimental effects on cognitive function in older adults, supporting the importance of minimizing exposure to toxic metals while ensuring adequate intake of essential elements for cognitive health.