The processes and mechanisms between obesity and onset of clinical disease are complex and somewhat unknown. Recently, findings from studies have indicated that obesity increases risk of all cause dementia, Alzheimer's disease, cerebral atrophy, and white matter hyperintensity. Given the current epidemic of obesity, and the expected age-related increase in dementia, even a modest association between these two conditions would have far reaching public health implications. Adipose tissue secretes a variety of adipocytokines, which in turn impact lipid and glucose metabolism, proinflammatory cytokines, oxidative stress and endothelial function. Low levels of the adipocytokine adiponectin are associated with increased adiposity, high blood pressure, dyslipidemia, insulin sensitivity, and type.2 diabetes. These findings indicate that adiponectin may be protective against dementia or cognitive decline, although these associations are unexplored. Leptin, an adipocytokine also made by white adipose tissue regulates energy balance, and animal models suggest it is also implicated in learning and memory, as well as deposition of amyloid beta, a main component of neurofibrillary plaques in Alzheimer's disease. This proposal is for a prospective cohort study of obesity, adipocytokines and cognitive decline (both global and verbal episodic memory) over five years in a well characterized sample of elderly Latinos (N=1500). The goal of this proposal is to examine the associations between overall obesity, visceral obesity, leptin, adiponectin and levels of cognitive functioning, as well as cognitive decline in a cohort of elderly community dwelling Latinos. We hypothesize that: 1) those obese will have greater cognitive decline independent of diabetes and cardiovascular disease compared to those who are not obese, 2) that the effect of visceral adiposity (waist circumference) will be stronger than overall obesity ( as estimated by body mass index) 2) that those with high levels of leptin will have greater cognitive decline than those with low levels, and 3) that those with low levels of adiponectin will have greater cognitive decline than those with high levels . We will also explore whether these adipocytokines mediate the association between various indices of obesity and cognition. Since Latinos are at a higher risk for diabetes, and are more likely to have visceral adiposity, this is an important group in which to characterize the potential role of adipocytokines on cognition and cognitive decline. ? ?
| Whitmer, Rachel A; Quesenberry, Charles P; Zhou, Jufen et al. (2011) Timing of hormone therapy and dementia: the critical window theory revisited. Ann Neurol 69:163-9 |
| Whitmer, R A; Gustafson, D R; Barrett-Connor, E et al. (2008) Central obesity and increased risk of dementia more than three decades later. Neurology 71:1057-64 |
| Whitmer, Rachel A (2007) The epidemiology of adiposity and dementia. Curr Alzheimer Res 4:117-22 |
| Whitmer, Rachel A; Gunderson, Erica P; Quesenberry Jr, Charles P et al. (2007) Body mass index in midlife and risk of Alzheimer disease and vascular dementia. Curr Alzheimer Res 4:103-9 |
