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Journal of Aging Research
Volume 2011 (2011), Article ID 362189, 11 pages
http://dx.doi.org/10.4061/2011/362189
Research Article

Genetic Risk Factors for Longitudinal Changes in Structural MRI in Former Organolead Workers

1Rush University Alzheimer's Disease Center, Rush University Medical Center, Room 1038, Chicago, IL 60612, USA
2Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA
3Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
4Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
5Center for Health Research and Rural Advocacy, Geisinger Clinic, Danville, PA 17822, USA
6The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21278, USA
7Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
8Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
9Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21278, USA

Received 21 February 2011; Accepted 31 July 2011

Academic Editor: Sofia Madureira

Copyright © 2011 Bryan D. James et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study examined associations between polymorphisms in three genes, apolipoprotein E (APOE), angiotensin converting enzyme (ACE), and vitamin D receptor (VDR), and longitudinal change in brain volumes and white matter lesions (WML) as well as effect modification by cardiovascular factors and tibia lead concentrations. Two MRIs, an average of 5 years apart, were obtained for 317 former organolead workers and 45 population-based controls. Both regions-of-interest and voxel-wise analyses were conducted. APOE and genotypes were associated with less decline in white matter volumes. There was some evidence of interaction between genetic polymorphisms and cardiovascular risk factors (ACE and high-density lipoprotein; VDR and diabetes) on brain volume decline. The VDR FokI ff genotype was associated with an increase in WML (no association for APOE or ACE). This study expands our understanding of how genetic precursors of dementia and cardiovascular diseases are related to changes in brain structure.