Risk of lead exposure, subcortical brain structure, and cognition in a large cohort of 9- to 10-year-old children

BACKGROUND: Lead, a toxic metal, affects cognitive development at the lowest measurable concentrations found in children, but little is known about its direct impact on brain development. Recently, we reported widespread decreases in cortical surface area and volume with increased risks of lead exposure, primarily in children of low-income families. METHODS AND FINDINGS: We examined associations of neighborhood-level risk of lead exposure with cognitive test performance and subcortical brain volumes. We also examined whether subcortical structure mediated associations between lead risk and cognitive performance. Our analyses employed a cross-sectional analysis of baseline data from the observational Adolescent Brain Cognitive Development (ABCD) Study. The multi-center ABCD Study used school-based enrollment to recruit a demographically diverse cohort of almost 11,900 9- and 10-year-old children from an initial 22 study sites. The analyzed sample included data from 8,524 typically developing child participants and their parents or caregivers. The primary outcomes and measures were subcortical brain structure, cognitive performance using the National Institutes of Health Toolbox, and geocoded risk of lead exposure. Children who lived in neighborhoods with greater risks of environmental lead exposure exhibited smaller volumes of the mid-anterior (partial correlation coefficient [r(p)] = -0.040), central (r(p) = -0.038), and mid-posterior corpus callosum (r(p) = -0.035). Smaller volumes of these three callosal regions were associated with poorer performance on cognitive tests measuring language and processing speed. The association of lead exposure risk with cognitive performance was partially mediated through callosal volume, particularly the mid-posterior corpus callosum. In contrast, neighborhood-level indicators of disadvantage were not associated with smaller volumes of these brain structures. CONCLUSIONS: Environmental factors related to the risk of lead exposure may be associated with certain aspects of cognitive functioning via diminished subcortical brain structure, including the anterior splenium (i.e., mid-posterior corpus callosum).