Article

Proton Magnetic Resonance Spectroscopy in Adults with Childhood Lead Exposure

Cincinnati Children's Environmental Health Center at Cincinnati Children's Hospital Medical Center, Ohio 45229, USA.
Environmental Health Perspectives (Impact Factor: 7.03). 10/2010; 119(3):403-8. DOI: 10.1289/ehp.1002176
Source: PubMed

ABSTRACT Childhood lead exposure adversely affects neurodevelopment. However, few studies have examined changes in human brain metabolism that may underlie known adverse cognitive and behavioral outcomes.
We examined the association between mean childhood blood lead levels and in vivo brain metabolite concentrations as adults, determined by proton magnetic resonance spectroscopy (MRS) in a birth cohort with documented low-to-moderate lead exposure.
Adult participants from the Cincinnati Lead Study [n = 159; mean age (± SD), 20.8 ± 0.9 years] completed a quantitative, short-echo proton MRS protocol evaluating seven regions to determine brain concentrations of N-acetyl aspartate (NAA), creatine and phosphocreatine (Cr), cholines (Cho), myo-inositol, and a composite of glutamate and glutamine (GLX). Correlation and multiple linear regression analyses were conducted.
Mean childhood blood lead levels were associated with regionally specific brain metabolite concentrations adjusted for age at imaging and Full-Scale intelligence quotient. Adjusted analyses estimated for a unit (micrograms per deciliter) increase in mean childhood blood lead concentrations, a decrease of NAA and Cr concentration levels in the basal ganglia, a decrease of NAA and a decrease of Cho concentration levels in the cerebellar hemisphere, a decrease of GLX concentration levels in vermis, a decrease of Cho and a decrease of GLX concentration levels in parietal white matter, and a decrease of Cho concentration levels in frontal white matter.
Gray-matter NAA reductions associated with increasing childhood blood lead levels suggest that sustained childhood lead exposure produces an irreversible pattern of neuronal dysfunction, whereas associated white-matter choline declines indicate a permanent alteration to myelin architecture.

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    • "Moreover, lead has the ability to substitute for zinc that is involved in the regulation of genetic transcription through zinc-finger proteins or zinc-binding sites in receptor channels (Reddy and Zawia 2000). Changes in mechanisms that control gene expression during early neurodevelopment may lead to reduction of gray matter and alteration of myelin and consequent neurological pathologies in adults (Cecil et al. 2011). Another indirect effect of Pb on the brain involves disruption of thyroid hormone transport into the brain. "
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    • "As our retention percentages were reasonably similar to other prospective lead studies with adult follow-ups (Brubaker et al., 2010; Cecil et al., 2011; Mazumdar et al., 2011, 2012; Wright et al., 2009, 2008), a key issue plaguing such long-term studies is retaining enough participants (and power) to find small 'real' effects significant. While these issues may impact generalisability, this study is able to advance knowledge given its many strengths: it is one of the few prospective lead studies to follow a birth cohort over two decades (Cecil et al., 2011; Fergusson et al., 2008; Mazumdar et al., 2011, 2012), and is the only study to examine mental health symptoms and psychiatric diagnoses in young adulthood. Furthermore, its detailed prospective design has enabled us to adjust for many other aspects of the early childhood environment. "
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