Lead Exposure and Early Brain Development

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 DESCRIPTION (provided by applicant): Childhood lead exposure is associated with many adverse physical and mental health outcomes, including reduced cognitive ability and increased behavioral problems. These neurocognitive and neurobehavioral outcomes are broadly hypothesized to result from abnormalities in neurodevelopment. However, while investigations of early brain development report reduced neuronal growth and impaired white matter maturation (hypomyelination) in response to lead exposure, these studies have exclusively been performed in animals. It is unclear if, and how, these key neurodevelopmental processes are similarly altered in human children; and at what level of exposure abnormalities become significant. Thus, there are significant gaps in our knowledge regarding the neurotoxic actions of lead on the developing human brain, and how potential alterations ultimately give rise to cognitive deficits. This research aims to address these gaps by examining the relationships between blood lead level (BLL) and magnetic resonance imaging (MRI) measures of myelination and neurite (combined dendrites and axons) density in a preliminary longitudinal study following children from 12 to 24 months of age. As a first step, we will recruit 36 healthy toddlers between 10 and 14 months of age with blood lead levels between 0 and 10μg/dL, who will receive MRI and a comprehensive cognitive and behavioral assessment. BLL, MRI and neuropsychological assessments will be repeated at 12 month follow-up. From this complement of data, we will investigate the relationships linking BLL, brain structure, and cognitive ability t each age-point; as well as the relationships between the longitudinal changes in each of these measures. This study will provide the first and earliest evidence of brain structure alteration in children with varying degrees of lead exposure, and establish their relationship to concurrent measures of cognitive and behavioral functioning. We hypothesize that increased levels of blood lead will be significantly associated with reduced myelin and neurite content, and that these structural abnormalities will mediate the relationship between blood lead levels and cognitive ability. This preliminary investigation will provide crucial new insight into a pressing public health issue that carries significant social and economic cost. Results are anticipated to have far reaching consequences in regard to current screening and prevention policies.