Associations of internal exposure to organophosphate esters and their metabolites with cognitive functions in middle-aged and elderly people: the mediating effects of inflammation

• OPEs and mOPEs were frequently detected in serum of middle-aged and elderly people. • Serum levels of certain OPEs/mOPEs were negatively correlated with MMSE and MoCA scores. • OPEs/mOPEs might impair cognitive functions in middle-aged and elderly people. • Females were more sensitive to the impairment of OPEs/mOPEs than males. • Inflammation partly mediates the association between OPE/mOPE exposure and cognition. Organophosphate esters (OPEs) are widely used chemicals, whereas the environmental contamination caused by OPEs and their metabolites (mOPEs) leads to human exposure and health risks. In this study, a cross-sectional analysis was conducted to investigate the serum levels of twelve OPEs and six mOPEs in middle-aged and elderly individuals residing in Beijing, China. The association between serum levels of OPEs/mOPEs and cognitive functions, as well as the mediating effect of inflammation, was explored. OPEs and mOPEs were widely detected in serum from 1,061 participants, and median concentrations of ΣOPEs + mOPEs, ΣOPEs, and ΣmOPEs were 48.73, 20.22, and 21.78 pmol/L, respectively. Serum levels of nine OPEs and mOPEs were negatively associated with cognitive scores in the whole population. For these compounds, for every increase of one quartile in their serum levels, cognitive scores reduced by 0.01–0.42 points. Stratified analysis showed that female participants are more sensitive to OPE/mOPE exposure than males. Moreover, educational level, age, and body mass index (BMI) may affect the associations between OPE/mOPE exposure and cognitive function. Two inflammation-related biomarkers, 5-hydroxytryptamine (5-HT) and plasma toll-like receptor 2 (TLR2), showed significant mediating effects in the influence of OPEs/mOPEs on cognitive function. The exposure of some OPEs and mOPEs can reduce cognitive scores by influencing 5-HT and TLR2, with mediating effect ratios to the total effect ranging from 5.4 % to 53.3 %. These findings provide evidence for understanding the impact of OPEs/mOPEs on cognitive function in the aging population.