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IS MRI-BASED VOLUME A MEDIATOR OF THE ASSOCIATION OF CUMULATIVE LEAD DOSE WITH COGNITIVE FUNCTION?

• Brian S. Caffo, Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health
• Sining Chen, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health
• Walter Stewart, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health and Center for Health Research and Rural Advocacy, Geisinger Clinic
• Karen Bolla, Department of Neurology, Johns Hopkins School of Medicine
• David Yousem, The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine
• Christos Davatzikos, Department of Radiology, University of Pennsylvania School of Medicine
• Brian S. Schwartz, Departments of Environmental Health Sciences and Epidemiology, Johns Hopkins Bloomberg School of Public Health and Department of Medicine, Johns Hopkins School of Medicine

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Abstract:

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.

Subject Area:

Epidemiology

Suggested Citation:

Brian S. Caffo, Sining Chen, Walter Stewart, Karen Bolla, David Yousem, Christos Davatzikos, and Brian S. Schwartz, "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.
http://www.bepress.com/jhubiostat/paper140