The impact of metals on cognitive impairment in the elderly and the mediating role of oxidative stress: A cross-sectional study in Shanghai, China.

Cognitive impairment (CI) is a prodrome of many neurodegenerative diseases with complex and unclear pathogenesis. Metal exposure has been found to be associated with CI, but existing population studies are scarce and have the limitations of single outcome and ignoring mixed exposures. This cross-sectional study was conducted in Shanghai, China, enrolling 836 seniors aged over 60 years to investigate the relationship between combined metal exposure (Lead (Pb), cadmium (Cd), and mercury (Hg)) and CI in the elderly and the mediating effect of oxidative stress. It was found that there were significant differences in urinary Pb, Cd, Hg and blood Pb levels between the CI and normal groups. Urinary Pb and Cd levels were significantly negatively correlated with Montreal Cognitive Assessment (MoCA) score, amyloid β ₄₂ (Aβ ₄₂ ) _, and Aβ _42/40 , while urinary Cd, Hg and blood Hg were significantly positively correlated with phosphorylated tau protein (P-tau). Weighted quantile sum (WQS) regression indicated that combined metal exposure had a more significant effect on CI than individual exposure. Mediation modeling revealed that plasma superoxide dismutase (SOD) was involved in the effects of urinary Cd on Aβ _42/40 and P-tau, with mediation effects accounting for 20 % of the total effect. This study emphasized the combined exposure to metals, and the results can help to properly understand the association between mixed metals exposure and CI in the elderly, as well as provide population data and theoretical basis for identifying early environmental risk factors and discovering potential mechanisms of CI.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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