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Historically, there has been minimal concern about the effect of adult lead exposure on the brain. Evidence from recent longitudinal studies raise concerns about the long-term effects of past exposure.We initiated three independent longitudinal studies to determine whether cumulative lead exposure was associated with persistent or progressive brain effects. The studies include 1,109 former U.S. organolead manufacturing workers, 803 current and former inorganic lead workers in Korea, and 1,140 50- to 70-year-old Baltimore residents with environmental lead exposure. The organolead workers had past exposure to inorganic and tetraethyl lead (TEL); in the other two studies, exposure was to inorganic lead. In each of these studies, we measured blood lead and tibia and patella lead by 109Cd K-shellinduced X-ray fluorescence.Higher tibia lead was consistently associated with poorer measures of cognitive function. Longitudinal analysis of the Korean and organolead cohort indicate that the effect of lead is persistent. Moreover, MRI data on organolead workers indicates a possible progressive effect from past exposure; higher tibia lead was associated with lower brain volume. The latter study indicates that a difference in tibia lead equivalent to about onesixth of the overall range was associated with a mean difference in these cognitive tests that was equivalent, on average, to what was observed for a five-year age difference.Our data suggest that a significant proportion of what is considered to be “normal” age-related cognitive decline may, in fact, be due to past exposure to neurotoxicants such as lead. Am. J. Ind. Med. 50:729-739, 2007. © 2007 Wiley-Liss, Inc.