Faculty Bibliography

Parkinson disease (PD) and Alzheimer disease (AD), the two most common neurodegenerative disorders in American adults, are of purely genetic origin in a minority of cases and appear in most instances to arise through interactions among genetic and environmental factors. In this article we hypothesize that environmental exposures in early life may be of particular etiologic importance and review evidence for the early environmental origins of neurodegeneration. For PD the first recognized environmental cause, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), was identified in epidemiologic studies of drug abusers. Chemicals experimentally linked to PD include the insecticide rotenone and the herbicides paraquat and maneb; interaction has been observed between paraquat and maneb. In epidemiologic studies, manganese has been linked to parkinsonism. In dementia, lead is associated with increased risk in chronically exposed workers. Exposures of children in early life to lead, polychlorinated biphenyls, and methylmercury have been followed by persistent decrements in intelligence that may presage dementia. To discover new environmental causes of AD and PD, and to characterize relevant gene-environment interactions, we recommend that a large, prospective genetic and epidemiologic study be undertaken that will follow thousands of children from conception (or before) to old age. Additional approaches to etiologic discovery include establishing incidence registries for AD and PD, conducting targeted investigations in high-risk populations, and improving testing of the potential neurologic toxicity of chemicals

Methyl mercury is a developmental neurotoxicant. Exposure results principally from consumption by pregnant women of seafood contaminated by mercury from anthropogenic (70%) and natural (30%) sources. Throughout the 1990s, the U.S. Environmental Protection Agency (EPA) made steady progress in reducing mercury emissions from anthropogenic sources, especially from power plants, which account for 41% of anthropogenic emissions. However, the U.S. EPA recently proposed to slow this progress, citing high costs of pollution abatement. To put into perspective the costs of controlling emissions from American power plants, we have estimated the economic costs of methyl mercury toxicity attributable to mercury from these plants. We used an environmentally attributable fraction model and limited our analysis to the neurodevelopmental impacts--specifically loss of intelligence. Using national blood mercury prevalence data from the Centers for Disease Control and Prevention, we found that between 316,588 and 637,233 children each year have cord blood mercury levels > 5.8 microg/L, a level associated with loss of IQ. The resulting loss of intelligence causes diminished economic productivity that persists over the entire lifetime of these children. This lost productivity is the major cost of methyl mercury toxicity, and it amounts to $8.7 billion annually (range, $2.2-43.8 billion; all costs are in 2000 US$). Of this total, $1.3 billion (range, $0.1-6.5 billion) each year is attributable to mercury emissions from American power plants. This significant toll threatens the economic health and security of the United States and should be considered in the debate on mercury pollution controls

A growing body of research supports the role of outdoor air pollutants in acutely aggravating chronic diseases in children, and suggests that the pollutants may have a role in the development of these diseases. This article reviews the biologic basis of children's unique vulnerability to highly prevalent outdoor air pollutants, with a special focus on ozone, respirable particulate matter (PM 2.5 [<2.5 microm in diameter] and PM 10 [<10 microm in diameter]), lead, sulfur dioxide, carbon monoxide, and nitrogen oxides. We also summarize understanding regarding health effects and molecular mechanisms of action. Practitioners can significantly reduce morbidity in children and other vulnerable populations by advising families to minimize pollutant exposures to children with asthma, or at a broader level by educating policymakers about the need to act to reduce pollutant emissions. Management of children with asthma must expand beyond preventing exposures to agents that directly cause allergic reactions (and therefore can be diagnosed by means of skin tests) and must focus more attention on agents that cause a broad spectrum of nonspecific, generalized inflammation, such as air pollution