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From the Center for Health Research and Rural Advocacy (W.F.S.), Geisinger Clinic, Danville, PA; Departments of Environmental Health Sciences (B.S.S., W.S.) and Epidemiology (W.F.S., B.S.S.), the Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Radiology (C.D., D.S., D.L., X.W.), the University of Pennsylvania, Philadelphia; Department of Community and Preventive Medicine (A.C.T.), Mount Sinai School of Medicine, New York, NY; and Department of Psychiatry (S.B.) and The Russell H. Morgan Department of Radiology and Radiological Sciences (D.Y.), the Johns Hopkins School of Medicine, Baltimore, MD.
Address correspondence and reprint requests to Dr. Walter Stewart, Geisinger Health System, Center for Health Research and Rural Advocacy, MC 30-03,100 N. Academy Ave, Danville, PA 17822; e-mail: wfstewart{at}geisinger.edu
Objective: To determine whether cumulative lead dose in former organolead workers was associated with MRI measures of white matter lesions (WML) and global and structure-specific brain volumes.
Methods: MRIs, tibia lead, and other measures were obtained from 532 former organolead workers with a mean age of 56 years and a mean of 18 years since last occupational exposure to lead. Cumulative lead dose was measured by tibia lead, obtained by X-ray fluorescence, and expressed as µg lead per gram of bone mineral (µg Pb/g). WML were evaluated using the Cardiovascular Health Study grading scale. A total of 21 global and specific brain regions were evaluated.
Results: A total of 36% of individuals had WML grade of 1 to 7 (0 to 9 scale). Increasing peak tibia lead was associated with increasing WML grade (p = 0.004). The adjusted OR for a 1 µg Pb/g increase in tibia lead was 1.042 (95% CI = 1.021, 1.063) for a CHS grade of 5+ (
5 vs <5). In linear regression, the coefficient for tibia lead was negative for associations with all structures. Higher tibia lead was significantly related to smaller total brain volume, frontal and total gray matter volume, and parietal white matter volume. Of nine smaller specific regions of interest, higher tibia lead was associated with smaller volumes for the cingulate gyrus and insula.
Conclusions: These data suggest that cumulative lead dose is associated with persistent brain lesions, and may explain previous findings of a progressive decline in cognitive function.
Editorial, see page 1464
Supported by grant RO1 AG10785 from the National Institute on Aging (NIA). Article content is solely the responsibility of the authors and does not necessarily represent official views of the NIA.
Disclosure: The authors report no conflicts of interest.
Received August 22, 2005. Accepted in final form February 7, 2006.
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