A Multimodal Magnetic Resonance Study of the Effects of Childhood Lead Exposure on Adult Brain Structure

INTRODUCTION: Lead is a potent environmental toxicant. Childhood lead exposure is associated with persistent cognitive and behavioral deficiencies, suggesting underlying neuroanatomic changes. This dissertation is an investigation of the effects of childhood lead exposure on young adult gray matter volume and white matter structure.

METHODS: We investigated a subset of the long-running Cincinnati Lead Study, a prospective birth cohort study investigating the effects of environmental lead exposure on a primarily black, urban inner-city cohort. Participants received 23 serial assessments of blood lead concentration during childhood, high-resolution volumetric magnetic resonance imaging at approximately 21 years of age, and diffusion tensor imaging at approximately 24 years of age. Associations between gray matter volume and mean childhood blood lead, and yearly mean blood lead levels from years 1 to 6, were investigated by adjusted voxel-wise multiple regression analysis using voxel-based morphometry (VBM) techniques. Associations between mean childhood lead levels and white matter diffusivity changes were investigated using adjusted multiple regression analyses.

RESULTS: Mean childhood lead levels were associated with significant adult gray matter volume loss, particularly in the frontal lobes, and particularly in men.

Analysis of yearly mean blood lead levels revealed that blood levels later in childhood were more strongly associated with adult gray matter volume loss than earlier blood lead levels. The most extensive and significant regions of lead-associated gray matter volume loss were found in the frontal lobes of men associated with lead levels measured later at 5 and 6 years of age.

Investigation of white matter diffusivity changes by diffusion tensor imaging analysis revealed widespread changes in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. The observed patterns of diffusivity changes was consistent with significant axonal dysfunction or demyelination in anterior-poster association bundles including the superior corona radiata, and increases in myelination or fiber diameter in commissural fibers of the corpus callosum.

CONCLUSIONS Childhood lead exposure is associated with significant, persistent adult gray matter volume loss and changes in white matter structure and integrity.