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.
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