Proton Magnetic Resonance Spectroscopy in Adults with Childhood Lead Exposure.

Background: Childhood lead exposure adversely affects neurodevelopment. However, few studies have examined changes in human brain metabolism that may underlie known adverse cognitive and behavioral outcomes. Objective: We examined the association between mean childhood blood lead levels and in vivo brain metabolite concentrations as adults determined by proton magnetic resonance spectroscopy (MRS) in a birth cohort with documented low-to-moderate lead exposure. Methods: Adult participants from the Cincinnati Lead Study (N=159, mean age (SD) 20.8 + 0.9 years) completed a quantitative, short echo proton MRS protocol evaluating seven regions to determine brain concentrations of N-acetyl aspartate (NAA), creatine and phosphocreatine (Cr), cholines (Cho), myo-inositol (mI), and a composite of glutamate and glutamine (GLX). Correlation and multiple linear regression analyses were conducted. Results: Mean childhood blood lead levels were associated with regionally specific, brain metabolite concentrations adjusted for age at imaging and full scale intelligence quotient (FSIQ). Adjusted analyses estimated for a unit (μg/dL) increase in mean childhood blood lead concentrations, a decrease of NAA and Cr concentration levels in the basal ganglia, a decrease of NAA and a decrease of Cho concentration levels in the cerebellar hemisphere, a decrease of GLX concentration levels in vermis, a decrease of Cho and a decrease of GLX concentration levels in parietal white matter, and a decrease of Cho concentration levels in frontal white matter. Conclusions: Gray matter NAA reductions associated with increasing childhood blood lead levels suggests that sustained childhood lead exposure produces an irreversible, pattern of neuronal dysfunction while associated white matter choline declines indicate a permanent alteration to myelin architecture.