Protective Role of Multiple Essential Minerals Against Cadmium-Related Cognitive Decline in Middle-Aged and Older Adults: A Prospective Study

<b>Background:</b> Cadmium (Cd) exposure is linked to cognitive decline in middle-aged and older adults, but the modifying role of essential minerals is unclear. This study aimed to identify key protective minerals and quantify their joint antagonistic effect against Cd neurotoxicity. <b>Methods:</b> Baseline serum minerals and urinary Cd were measured in 6795 adults (≥40 years) from the 2015 China Health and Nutrition Survey. Cognitive function (MMSE) was assessed after 3 years. Associations were analyzed using multiple linear regression and Quantile g-computation (QGC) for joint effects. Combined exposure groups and interaction terms were assessed. Restricted cubic spline (RCS) models explored potential nonlinear dose-response relationships. <b>Results:</b> Participants in the highest urinary Cd quartile had significantly lower MMSE score (β = -0.09, 95% CI: -0.15, -0.02) than the lowest quartile. Serum calcium (Ca), ferrum (Fe), magnesium (Mg), selenium (Se), and phosphorus (P) were positively associated with MMSE. QGC revealed that the joint effect of Cd and the 5-mineral mixture (β = 0.10, 95% CI: 0.05, 0.14) was weaker than the protective effect of the 5-mineral mixture. Any high-mineral group had significantly higher MMSE score compared to the high-Cd/low-mineral group. <b>Conclusions:</b> Essential minerals Ca, Fe, Mg, Se, and P effectively antagonize Cd-associated cognitive decline. Their combined exposure demonstrates significant protective effects, providing key evidence for precision nutrition and environmental health risk management in Cd-exposed populations.