Neurotransmitter\nMetabolism in Arsenic Exposure-Induced\nCognitive Impairment: Emerging Insights and Predictive Implications

Scholars have long been interested in the association\nbetween arsenic\n(As) exposure and neurological disorders; however, existing systematic\nepidemiological investigations are insufficient and lack the inclusion\nof diagnostic or predictive biological markers. This study sought\nto evaluate the association between As exposure and cognitive impairment\nand identify potential biomarkers by developing predictive models.\nHere, we found that logarithm (Ln)-transformed urinary As concentrations\nwere negatively linearly related to the mini-mental state examination\n(MMSE) score exposure–response curves. Subsequently, we identified\na unique plasma neurometabolite profile in subjects exposed to As\ncompared with the reference group. Further analyses showed that tryptophan,\ntyrosine, dopamine, epinephrine, and homovanillic acid were all significantly\nassociated with both urinary As concentrations and MMSE scores. Notably,\nthe association between As exposure and MMSE scores was partly mediated\nby tryptophan, tyrosine, dopamine, and epinephrine. Importantly, an\nunprecedented prediction model utilizing neurotransmitters was established\nto assess the risk of cognitive impairment due to As exposure. A 91.1%\nconsistency rate was found between the predicted and the actual probabilities.\nAdditionally, machine learning models also produced highly accurate\npredictions. Overall, this study revealed a dose-dependent cognitive\ndecline in As-exposed adults accompanied by a disturbance in the signature\nof neurotransmitter metabolites, offering new predictive insights.