Neurobehavioral function and low-level metal exposure in adolescents: suggestive evidence of an association between blood copper and attention

Abstract

Background It is widely acknowledged that an excessive metal exposure is harmful to the brain. However, many aspects of metal neurotoxicity remain unclear including a determination of the magnitude of the low-level exposure effects and the establishment of exposure levels which can be assumed safe. Attention and the motor function are important targets of metal neurotoxicity. Aims To investigate the association between metal exposure indicators (in blood: copper, cadmium, lead, manganese, thallium; in urine: arsenic, cadmium, nickel; in hair: methylmercury) and the neurobehavioral endpoints attention and motor speed in a group of 606 adolescents between 13.6 and 17 years of age. Methods We applied structural equation modeling, a statistical method that allows to account for measurement errors and to specify a model in terms of causal relationships. Our models took into account gender, age, socio-economic status, education of mother, education of father, and smoking behavior of the adolescents. A quadratic model was applied for the essential elements copper and manganese and a linear model for the remaining metals. Results We observed an inverted U-shape association between copper exposure and attention, p=0.002. The highest attention scores was estimated for a whole blood copper concentration of 543 µg/L (95% CI: 300-983). For a whole blood copper concentration of 1035 µg/L (the 95th percentile), the attention score was 0.50 standard deviation lower compared to the optimum level. Lead, methylmercury, toxicologically relevant arsenic, manganese, cadmium, thallium, and nickel did not show a significant association, neither with attention nor with manual motor speed. Conclusions Blood copper and attention showed an inverted U-shape association in adolescents. Our study did not provide evidence of neurotoxicity from other metals. Our results are in line with recent evidence based on adults and elderly suggesting that copper might be relevant for the neurobehavioral function in humans.