BACKGROUND: Associations between exposure to single metals and cognitive impairment or related outcomes have been reported in many previous studies. However, co-exposure to more than one metal is common situation. In recent years, studies on the effects of exposure to multiple metals on cognitive impairment or related outcomes have increased, but remain very limited, with a focus on populations with occupational exposure to metals, children, and adolescents. The potential relationships between exposure to metal mixtures and risk of cognitive impairment in adults remain to be clarified. OBJECTIVE: To determine the associations between blood metal mixtures and cognitive impairment risk. METHODS: Inductively coupled plasma mass spectrometry (ICP-MS) was utilized to detect the blood levels of lead (Pb), iron (Fe), copper (Cu), calcium (Ca), magnesium (Mg), and zinc (Zn). Multivariable logistic regression and Bayesian kernel machine regression (BKMR) models were employed to assess the relationships of exposure to these blood metal mixtures with the risk of cognitive impairment. RESULTS: It was found that four metals (Pb, Fe, Cu, and Mg) were positively correlated with cognitive impairment in each single metal model. The association of Pb and Cu remained significant after adjusting for these six metals, with the odds ratios (95% confidence intervals) in the highest quartiles of 9.51 (4.41-20.54, p-trend <
0.01) and 4.87 (2.17-10.95, p-trend <
0.01), respectively. The BKMR models indicated that co-exposure levels of Ca, Cu, Fe, Mg, Pb, and Zn were related to increased risk of cognitive impairment at ≥25th percentile compared with median, and Pb and Cu mainly contributed to the joint effect. In addition, the interaction effects of Mg and Pb/Pb and Cu on the risk of cognitive impairment were observed. SIGNIFICANCE: Co-exposure of six metals (Pb, Fe, Cu, Ca, Mg, and Zn) increased the risk of cognitive impairment in Chinese adults, with Pb and Cu likely to have greater impact. Potential interaction effects of Mg and Pb, Pb and Cu on the risk of cognitive impairment may exist.