Cognitive function (CF) is central to daily functioning and quality of life. The life course trajectory in CF is known to vary by race/ethnicity and socioeconomic status (SES), and this variation involves a complex causal web. Unpacking this causal web has important political, social, and public health implications, and provides a foundation for prevention and for ensuring social equity. However, we have only a rudimentary understanding of the factors that mediate these disparities in CF. The causal web is complex and involves such diverse and possibly interrelated domains as genetic, social, behavioral, environmental, contextual factors, and individual vascular health. The direct and indirect contributions of these diverse factors must be considered in trying to explain variation by race/ethnicity and SES, moving beyond the traditional but somewhat limiting exploration of """"""""gene-environment interactions"""""""" by more broadly defining the underpinnings of these disparities. Ubiquitous potential causes of a decline in CF in older adults include lead exposure, apolipoprotein E (ApoE) genotype, vascular risk factors (i.e., blood pressure), and health-compromising behaviors (e.g., inactivity and smoking). Importantly, a number of genes known to differ by race/ethnicity appear to influence the toxicokinetics or toxicity of lead, including those for the 8-aminolevulinic dehydratase (ALAD), vitamin D receptor (VDR), Na/K ATPase (NKATP), and ApoE genes. Disparities in CF must be examined using next-generation data and methods that allow the modeling of the causal structure of these multiple domains, and to see how and to what extent social, behavioral, and contextual factors are important mediators and moderators along an extended causal pathway. Only by testing this more complete model, will it be possible to fully explicate the complex multilevel associations that pattern everyday life. The goal of this research is to understand the direct and indirect influences of lead absorption, four specific genes, individual social and behavioral factors, contextual factors, and blood pressure in accounting for the associations of race/ethnicity and SES with CF and cognitive decline. The investigators propose a five-year prospective study of 900 urban residents, aged 50 to 70 years, randomly selected from specific geographic areas with variation in race/ethnicity and SES. All study subjects will have three visits at 16-month intervals, with measurement of cognitive function, blood pressure, tibial lead, patellar lead, individual social and behavioral factors, current and past contextual factors, and ALAD, VDR, NKATP, and ApoE genotypes.
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