Exposure to Multiple Metals and Cerebral White Matter Hyperintensity in Chinese Population: A Cross-Sectional Study

BACKGROUND: Evidence about the impact of multiple metal exposure on brain neuroimaging metrics remains limited. We aim to investigate the effects of single and mixed metal exposure on white matter hyperintensities (WMHs). METHODS: This cross-sectional study included 1183 subjects without stroke history from the META-KLS (Multi-modality Medical Imaging Study Based on Kailuan Study), which is an existing prospective cohort in Tangshan, China. Plasma metal levels, including Mg, Ca, V, Mn, Co, Ni, Cu, Zn, As, Se, Rb, Cs, Tl, Pb, and Cd, were measured using an inductively coupled plasma mass spectrometer. Ordinal and binary logistic regression models were used to examine the effects of metal exposure on the WMH burden, deep white matter hyperintensity, and periventricular white matter hyperintensity. All metal concentrations were naturally log-transformed to reduce skewness and were analyzed as both continuous and tertile forms. Weighted quantile sum regression, quantile-based g-computation model, and Bayesian Kernel Machine Regression were used in the metal mixture analysis. RESULTS: Compared with the first tertile, the adjusted odds ratios and 95% CIs for the WMH burden in the third tertile were 1.57 (1.05–2.34) for As, 2.01 (1.28–3.18) for Cu, 1.68 (1.14–2.50) for V, 1.61 (1.07–2.44) for Cs, and 1.56 (1.04–2.34) for Tl (all P for trend<0.05). Additionally, Pb, Se, and Mg showed significant positive associations with WMH burden exclusively in continuous analysis, with odds ratios of 1.27 (1.02–1.56) for Pb, 1.32 (1.07–1.61) for Se, and 1.27 (1.04–1.55) for Mg for per interquartile range increase in Ln-transformed metal concentrations. The weighted quantile sum index revealed a significant positive correlation with WMH burden risk (each interquartile range increment in the weighted quantile sum index was associated with 60% higher odds for WMH burden [95% CI, 1.09–2.34]). The primary contributors to the weighted quantile sum index were As (39.4%), followed by Pb (12.5%) and Cu (11.3%). The bivariate exposure-response relationships suggested potential interactions between As and Cu, as well as As and Co. CONCLUSIONS: There were positive associations between individual exposures to As, Pb, Cu, V, Se, Cs, Tl, and Mg, and mixed metal exposure with WMH burden among the Chinese population, strengthening the evidence of detrimental effects of specific metals on brain health.