The Heart of Medicine

Wright et al. 2003). These effects have been assessed using primarily behavioral and neu-ropsychologic evaluations and are some of the most consistently reported impairments associated with lead exposure. Regarding the molecular and cellular effects of lead exposure that may underlie the behavioral effects, there is a good deal of data from experimental studies in animals, but relatively little is known about the structural and functional correlates of lead-related brain dysfunction in humans. A better understanding of the underlying pathology would not only have potential benefits for prevention and treatment of the adverse effects but could also help identify those effects specifically attributable to lead. Magnetic resonance spectroscopy (MRS) provides a noninvasive method with which to monitor biochemical aspects of acute and chronic stages of neurologic disease in the human brain (Ross et al. 2006). The development of spatially localized spectroscopic methods that sample the relative levels of metabolites from volumes of tissue defined from magnetic resonance imaging (MRI) scans has provided a basis for integrating the biochemical information obtained by MRS with the anatomical and pathological information obtained from MRI. MRS has been used as a method for assessing both neuronal viability and demyelination. The use of MRS in neurologic disease has grown rapidly over the past decade, but the use of MRS in the setting of environmental insult to the brain is quite new. Earlier MRS studies of lead-exposed individuals do suggest effects on brain metabolites, but these studies focused on small numbers of very highly exposed children (Meng et al. 2005; Trope et al. 1998, 2001). Examination of the effects of exposure levels to which a much larger population would be exposed have not been done. We assessed the association between cumulative exposure to lead—as measured with K-X-ray fluorescence (KXRF) of bone lead—and brain metabolite ratios measured with MRS among participants in the Department of Veterans Affairs' (VA) Normative Aging Study (NAS), a community-based cohort of elderly U.S. men with lead exposure similar to a similarly aged cross-section of the general U.S. population. Methods Study population. This research was conducted on a subgroup of the VA NAS, a multidisciplinary longitudinal study of aging in men established by the VA in 1963 (Bell et al. 1966). The research herein was approved by the Human Subjects Committees of the Boston VA Medical Center, the Brigham and Women's Hospital, and the Harvard School of Public Health. This cohort has been described …