title: Past adult lead exposure is linked to neurodegeneration measured by brain MRI.
abstract: 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 microg lead per gram of bone mineral (microg 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 microg Pb/g increase in tibia lead was 1.042 (95% CI = 1.021, 1.063) for a CHS grade of 5+ (> or = 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.
authors.affiliation: Center for Health Research and Rural Advocacy, Geisinger Clinic, Danville, PA 17822, USA. wfstewart@geisinger.edu
authors.forename: W F
authors.initials: WF
authors.lastname: Stewart
authors.forename: B S
authors.initials: BS
authors.lastname: Schwartz
authors.forename: C
authors.initials: C
authors.lastname: Davatzikos
authors.forename: D
authors.initials: D
authors.lastname: Shen
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: A C
authors.initials: AC
authors.lastname: Todd
authors.forename: W
authors.initials: W
authors.lastname: Shi
authors.forename: S
authors.initials: S
authors.lastname: Bassett
authors.forename: D
authors.initials: D
authors.lastname: Youssem
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000187:drug effects*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000737:chemistry / Q000473:pathology; D002617:Chemical Industry; D003072:Cognition Disorders / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology; D015331:Cohort Studies; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D006179:Gyrus Cinguli / Q000737:chemistry / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D007855:Lead Poisoning / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology* / Q000523:psychology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009186:Myelin Sheath / Q000737:chemistry / Q000473:pathology*; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D009483:Neuropsychological Tests; D009784:Occupational Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology*; D009929:Organ Size; D011446:Prospective Studies; D016037:Single-Blind Method; D012907:Smoking / Q000453:epidemiology; D013052:Spectrometry, X-Ray Emission; D011795:Surveys and Questionnaires; D013756:Tetraethyl Lead / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D013977:Tibia / Q000737:chemistry
chemical_list: D013756:Tetraethyl Lead; C014849:tetramethyllead