The association of lead exposure and motor performance mediated by cerebral white matter change

The goals were to determine if lead exposure is associated with cerebral white matter changes (WMC) and if so, does WMC mediate the relation between lead and psychomotor slowing as measured by Grooved Pegboard (GP). In the literature, age is the strongest predictor of WMC and therefore 61 lead smelter workers age 50 and under were included in the study population. Mean (range) age was 40 (23-50) years, years of education was 9 (0-13), duration of employment was 19 (1-26), current blood lead (PbB) was 29 (16-42) microg/dl, working lifetime weighted integrated blood lead (IBL) was 826 (65-1451) microg year/dl, working lifetime weighted average blood lead (TWA) was 42 (17-59) microg/dl, and bone lead (PbBn) was 39 (-12-90) microg Pb/g bone mineral. WMC, recorded as hyperintensities on T2-weighted MRI of the brain were graded. Lead variables were entered in a logistic regression attempting to differentiate normal versus abnormal MRI, after controlling for age and cerebrovascular risk factors. Direct effects of lead on GP and indirect effects of lead on GP through WMC was modeled using multiple linear regression analyses after controlling for the covariates. WMC were present in 23% of MRIs. Logistic regression of WMC on lead exposure metrics demonstrated significantly elevated odds ratios for IBL, TWA, and PbBn after the covariates. Of the lead exposure variables, IBL (beta=0.339, p<0.10) had a larger direct effect on GP after adjusting for the covariates than PbBn (beta=0.265, p<0.10). After adjusting for the lead term and covariates WMC accounted for an additional effect on GP performance after PbBn (beta=0.261, p<0.10) and after IBL (beta=0.278, p<0.05). Path analysis demonstrated that some of the relationship of both PbBn and IBL with GP is mediated by WMC.