Cognitive decline is a common, but not inevitable, accompaniment to aging. While much research is currently being directed at Alzheimer' s Disease -- one of the most severe expressions of cognitive decline -- relatively little work is currently aimed at identifying risk factors and mechanisms associated with early (i.e., subclinical) cognitive decline, even though this may be the stage most amenable to prevention. An important issue that needs to be clarified in relation to the etiology of cognitive decline is the role of environmental lead exposure and the interaction of lead with specific candidate genes. In this application we discuss how four candidate genes -- APOE, the HFE (hemochromatosis) gene, transferrin, and Tau protein -- may interact with lead burden to increase the risk for oxidative cell damage leading to neuronal cell loss and cognitive deficits. We review the last 11 years of our research on low-level lead toxicity and describe compelling preliminary data. We then propose a new study that calls for new data collection in our established Bostonarea cohorts [Normative Aging Study (NAS), Nurses Health Study (NHS), and Community Lead Study (CLS)].
Our specific aims are to test hypotheses related to the impact on cognition of lead burden and its potential interaction with our four polymorphisms of interest. We will look at cognition cross-sectionally and longitudinally, using a validated battery of telephone cognitive function assessment tools as well as a battery of in-person cognitive tests that we have been administering in person since 1993. Results of this research promise to shed further light on lead's potential impact on society and may also give rise to tools for identifying susceptible individuals as well as early brain effects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES005257-14
Application #
7115197
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Gray, Kimberly A
Project Start
1991-02-01
Project End
2008-07-31
Budget Start
2006-08-11
Budget End
2007-07-31
Support Year
14
Fiscal Year
2006
Total Cost
$645,187
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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