Abstract
Millions of Americans now entering midlife and old age were exposed to high levels of lead, a neurotoxin, as children. Evidence from animal-model and human observational studies suggest that childhood lead exposure may raise the risk of adult neurodegenerative disease, particularly dementia, through a variety of possible mechanisms including epigenetic modification, delayed cardiovascular and kidney disease, direct degenerative CNS injury from lead remobilized from bone, and lowered neural and cognitive reserve. Within the next ten years, the generation of children with the highest historical lead exposures, those born in the 1960s, 1970s, and 1980s, will begin to enter the age at which dementia symptoms tend to emerge. Many will also enter the age in which lead stored in the skeleton may be remobilized at greater rates, particularly for women entering menopause and men and women experiencing osteoporosis. Should childhood lead exposure prove pro-degenerative, the next twenty years will provide the last opportunities for possible early intervention to forestall greater degenerative disease burden across the aging lead-exposed population. More evidence is needed now to characterize the nature and magnitude of the degenerative risks facing adults exposed to lead as children and to identify interventions to limit long-term harm.