Multi-metal mixture exposure and cognitive function in urban older adults: The mediation effects of thyroid hormones

The existing studies on the association between multi-metal mixture exposure and cognitive function in the older adults are limited and controversial, with no studies considering the mediating effect of thyroid hormones on the connection between them. This study of 441 urban older adults assessed 21 urinary metal levels and cognitive function using the Mini-Mental State Examination (MMSE). Urinary metal levels were measured via inductively coupled plasma mass spectrometry (ICP-MS), and thyroid hormones levels were obtained from medical records. Mediation analysis evaluated the role of thyroid hormones in the link between metals exposure and cognitive function. The General Linear Model (GLM) showed negative correlations between MMSE scores and titanium (Ti), copper (Cu), rubidium (Rb), and molybdenum (Mo), and positive correlations with selenium (Se) and barium (Ba). Nonlinear inverse U-shaped associations between Mo, Rb, and MMSE scores were identified using Restricted Cubic Splines (RCS) and Bayesian Kernel Machine Regression (BKMR). Mediation analysis revealed that Free Thyroxine (FT4) mediated the relationship between Rb and MMSE scores by 29.10 % and between Zinc (Zn) and language performance by 35.00 %. Total thyroxine (TT4) mediated the link between Cu and orientation score by 24.69 %, and Thyroid Stimulating Hormone (TSH) mediated the association between Cu and attention score by 38.96 %. Ti, Se, Rb, Mo, Ba and Cu were significantly associated with cognitive impairment risk. Mixed exposure to Mo and Rb was linked to an increased risk of cognitive impairment. Additionally, levels of TSH, FT4 and TT4 were associated with cognitive function, mediating the effects of Rb, Zn and Cu on cognitive function. • Significant links were found between Ti, Cu, Rb, Mo, Se, Ba and cognitive function in elders. • Mixed metal exposure, notably Mo and Rb links to higher cognitive impairment risk. • Ba and Se might protect cognitive function from metal exposure effects in the elderly. • The nonlinear relationship between Mo, Rb and MMSE scores showed varying effects at different doses. • FT4, TSH and TT4 mediate the effects of Rb, Zn and Cu on MMSE scores.