Research has suggested that obesity may contribute to declines of cognitive function among the elderly. Whether obesity is independently associated to declines in cognitive function or whether it is a contributing risk factor among other cardiovascular and metabolic factors is unknown. Much of the existing literature has relied on cross-sectional data or has not accounted for cardiovascular and metabolic factors. Additionally, domains of cognitive function have been shown to be differentially susceptible to decline;however, most literature has only focused on global cognitive function. Elderly women are at higher risk for chronic disease and disability, and thus, have greater healthcare expenditures than compared to elderly men. Utilizing data from the Women's Health and Aging Study II, [a long-term observational study], this proposal will be the first to investigate the association of obesity and late life changes in domains of cognitive function among the high-risk population of elderly women. The goal of this research proposal is to explore the prospective relationship between obesity (measured by BMI and then by incorporating BMI with arm circumference and triceps skin fold measurements) and changes in domains of cognitive function (executive function, memory, and speed of processing), and to evaluate the plausible mechanisms of the observed association between obesity and cognitive function by examining a panel of inflammatory and metabolic mediators. The three specific aims are to 1.) Use exploratory analysis to examine the concurrent association of obesity and domains of cognitive function and to evaluate moderators of these relationships, including age, race, and education, 2.) To evaluate the prospective relationship of baseline obesity with changes across the cognitive domains, assessing population-average and subject specific cognitive changes by utilizing, respectively, GEE and Random Effects Modeling, and 3.) To explore potential inflammatory, metabolic, and vascular mediators of these observed relationships, including cortisol, lnterleukin-6, polymorphisms of APOE, and hemoglobin A1C. Identification and proper control for baseline covariates, understanding moderating and mediating pathways, and validating results will strengthen our understanding of the negative consequences of obesity on cognitive functioning in the elderly. Both obesity and cognitive function have been seperately identified to be associated with functional impairment among the elderly. Findings from this proposal may identify mechanisms linking obesity with cognitive function, thus [possibly] allowing for identification of intervention targets to reduce subsequent burden on affected individuals as well as societal health care expenditures.
