This work considers the pathway through which past occupational lead exposure impacts cognitive function using cross-sectional data. It is motivated by studies linking cumulative lead dose with brain volumes, volumes with cognitive function, and lead dose with cognitive function. It is hypothesized that the brain regions associated with lead mediate a portion of the association between lead dose and cognitive function. The data were derived from an ongoing study of 513 former organolead manufacturing workers. Using MRIs, a novel analysis was performed to investigate Mediation. Volumes associated with cognitive function and lead dose were derived using registered images and used in a subsequent mediation analysis. Cumulative lead dose was associated with adverse function in the visuo-construction, executive functioning and eye-hand coordination domains. Of these, there was strong evidence of volumetric mediation of lead’s effect on cognition in the visuo-construction domain, a moderate amount for eye-hand coordination, and limited evidence for executive functioning. A second path analysis based approach was also performed. To address the possibility that chance associations explained these findings, a permuted analysis was conducted, the results of which support the mediation inferences. The approach to the evaluation of volumetric mediation may have general applicability in epidemiologic neuroimaging settings.
Caffo, Brian S.; Chen, Sining; Stewart, Walter; Bolla, Karen; Yousem, David; Davatzikos, Christos; and Schwartz, Brian S., "IS MRI-BASED VOLUME A MEDIATOR OF THE ASSOCIATION OF CUMULATIVE LEAD DOSE WITH COGNITIVE FUNCTION?" (April 2007). Johns Hopkins University, Dept. of Biostatistics Working Papers. Working Paper 140.