We have recently completed a cross-sectional study examining the relation between occupational exposure tetraethyllead (TEL) and inorganic lead and cognitive function (CF). Associations were consistently observed with lead exposure duration and cumulative estimates of exposure and dose, primarily in three domains: verbal learning/memory, attention/concentration, and speed and accuracy of mental/motor executive functions. The cross-sectional data support prior animal studies and human case reports. Moreover, TEL is known to cause neurofibrillary tangles in animal models. However, to date there are no prospective data to provide support for a causal relation. The lead exposed study population is unique because extensive data are available to estimate cumulative exposure to lead. We propose to conduct a longitudinal study to examine change in CF in 400 current and former lead exposed workers compared to 400 age, education, and race frequency. matched population controls. All subjects will be 50 to 74 years of age at enrollment and examined four times over a 36 month period. Testing will consist of a comprehensive battery of neurobehavioral tests which will be used to assess a wide variety of cognitive and functional domains. In addition, olfactory function and peripheral vibration threshold will also be assessed. Our central objective is to determine whether the decline in cognitive function among lead exposed workers is greater than that expected from aging alone (as measured in frequency matched population controls) and, if so, whether the change is related to age at first exposure, time since first exposure, and time since last exposure. As a secondary aim, we propose to examine whether the differences we observe are functionally specific. The focus of this study is both of general interest in understanding the long term consequences of exposure to neurotoxins and relevant to models of degenerative changes observed in conditions like Alzheimer's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG010785-05
Application #
2516947
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1993-09-01
Project End
1998-12-31
Budget Start
1997-09-01
Budget End
1998-12-31
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Fisher, Aaron; Caffo, Brian; Schwartz, Brian et al. (2016) Fast, Exact Bootstrap Principal Component Analysis for p > 1 million. J Am Stat Assoc 111:846-860
Bobb, Jennifer F; Schwartz, Brian S; Davatzikos, Christos et al. (2014) Cross-sectional and longitudinal association of body mass index and brain volume. Hum Brain Mapp 35:75-88
James, Bryan D; Glass, Thomas A; Caffo, Brian et al. (2012) Association of social engagement with brain volumes assessed by structural MRI. J Aging Res 2012:512714
James, Bryan D; Caffo, Brian; Stewart, Walter F et al. (2011) Genetic risk factors for longitudinal changes in structural MRI in former organolead workers. J Aging Res 2011:362189
Swihart, Bruce J; Caffo, Brian; James, Bryan D et al. (2010) Lasagna plots: a saucy alternative to spaghetti plots. Epidemiology 21:621-5
Schwartz, Brian S; Caffo, Brian; Stewart, Walter F et al. (2010) Evaluation of cumulative lead dose and longitudinal changes in structural magnetic resonance imaging in former organolead workers. J Occup Environ Med 52:407-14
Chen, Sining; Wang, Chi; Eberly, Lynn E et al. (2009) Adaptive control of the false discovery rate in voxel-based morphometry. Hum Brain Mapp 30:2304-11
Schwartz, Brian S; Chen, Sining; Caffo, Brian et al. (2007) Relations of brain volumes with cognitive function in males 45 years and older with past lead exposure. Neuroimage 37:633-41
Shih, Regina A; Hu, Howard; Weisskopf, Marc G et al. (2007) Cumulative lead dose and cognitive function in adults: a review of studies that measured both blood lead and bone lead. Environ Health Perspect 115:483-92
Schwartz, Brian S; Hu, Howard (2007) Adult lead exposure: time for change. Environ Health Perspect 115:451-4

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