Obesity, Adipocytokines and Cognitive Aging

描述（由申请人提供）：肥胖和临床疾病发作之间的过程和机制是复杂的，有些未知。最近，研究结果表明，肥胖增加了所有原因痴呆、阿尔茨海默病、脑萎缩和白色物质高密度的风险。考虑到目前肥胖的流行，以及预期的与年龄相关的痴呆症增加，这两种情况之间即使是适度的关联也会对公共卫生产生深远的影响。脂肪组织分泌多种脂肪细胞因子，进而影响脂糖代谢、促炎细胞因子、氧化应激和内皮功能。低水平的脂肪细胞因子脂联素与增加肥胖，高血压，血脂异常，胰岛素敏感性和2型糖尿病。这些发现表明，脂联素可能对痴呆或认知能力下降有保护作用，尽管这些关联尚未被探索。瘦素是一种脂肪细胞因子，也由白色脂肪组织产生，调节能量平衡，动物模型表明它也与学习和记忆以及淀粉样蛋白β的沉积有关，淀粉样蛋白β是阿尔茨海默氏病中神经胶质斑块的主要成分。这项建议是一项前瞻性队列研究的肥胖，脂肪细胞因子和认知能力下降（包括全球和口头情景记忆）超过五年的一个很好的特点样本的老年拉丁美洲人（N=1500）。这项建议的目的是研究整体肥胖，内脏肥胖，瘦素，脂联素和认知功能水平之间的关联，以及老年社区居住的拉丁美洲人的认知能力下降。我们假设：1）与不肥胖的人相比，肥胖的人将有更大的认知能力下降，而不受糖尿病和心血管疾病的影响，2）内脏肥胖的影响（腰围）将强于整体肥胖（根据体重指数估计）2）瘦素水平高的人比瘦素水平低的人认知能力下降更大，和3）脂联素水平低的人比脂联素水平高的人认知能力下降更严重。我们还将探讨这些脂肪细胞因子是否介导肥胖和认知的各种指数之间的关联。由于拉丁美洲人患糖尿病的风险更高，更有可能患有内脏肥胖，因此这是一个重要的群体，可以表征脂肪细胞因子对认知和认知能力下降的潜在作用。

DESCRIPTION (provided by applicant): 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.