The goal of this work is to begin to identify biological mechanisms that contribute to neurocognitive deficits in children exposed to low-level lead. This research plan proposes to measure blood lead levels in a large population of minority and underserved children;compare neurocognitive functioning in children with and without detectable blood lead levels;and examine associations between selected genetic polymorphisms and neurocognitive performance in children exposed to low-level lead. Lead exposure is a significant health disparity. Low-level lead exposure has long been associated with diminished cognitive function, and may pose an unrecognized threat to the cognitive health and well-being of an unknown number of minority and underserved children. Moreover, previously unexamined common genetic differences may potentiate the neurotoxic effects of lead in children. Lead toxicity is diagnosed when a child's blood lead level (BLL) is >10 micrograms per deciliter (g/dL). According to the EPA however, a "Reference Dose" value, that is a concentration below which no adverse effects have been observed, is not available for lead. In response to over 40 studies showing diminished IQ in children with BLLs <10 g/dL, the CDC convened an expert committee in 2003 to critically examine the findings. The findings were unequivocally confirmed. But in its decision to maintain the 10 g/dL threshold, the committee cited the need for studies suggesting causative biological mechanisms. We do not yet understand the mechanisms by which low-level lead exposure causes neurocognitive decline in young children. This is a critical knowledge gap, which creates the risk of lower cognitive function and diminished quality of life, especially for minority and underserved children. As a result of this gap, child blood lead levels <10.0 g/dL are ignored. Our central hypothesis is that chronic low-level lead exposure impairs neurocognitive function through mechanisms that are genetically mediated. H1: 25% of minority children between the ages of 5 and 12 have "detectable" blood lead levels (4.0 - 9.9 g/dL);H2: as compared to children with "undetectable" blood lead levels, children with "detectable" blood lead levels perform more poorly on neurocognitive tasks associated with brain networks specifically vulnerable to lead;H3: children with "detectable" blood lead levels, and carrying one or both genetic polymorphisms, have lowest scores on tests of neurocognitive function. Findings from these studies may begin to suggest the numbers of minority and underserved children ages 5 - 12 currently exposed to low-level lead;which types of neurocognitive deficits result;and whether common genetic differences potentiate the neurotoxic effects of lead. The findings may also suggest new avenues for detection, primary prevention and intervention. PUBLIC HEALTH RELEVANCE: Lead exposure is a significant health disparity, low-level lead exposure has been associated with diminished cognitive function, and yet low-level lead exposure continues to be ignored, perhaps posing a hidden threat to the health and well-being of an unknown number of minority and underserved children. Common genetic differences may increase its neurotoxic effects. Findings from these studies may begin to suggest the numbers of currently exposed minority and underserved children ages 5 - 12 years, and which neurocognitive deficits result, while suggesting new avenues for detection and primary prevention.

R21HD060120

2009-04-09

2013-05-31