Obesity, Adipocytokines and Cognitive Aging

描述(由申请人提供)：肥胖和临床疾病发病之间的过程和机制是复杂的，有些未知。最近，研究结果表明，肥胖会增加各种原因引起的痴呆症、阿尔茨海默病、脑萎缩和脑白质过度强度的风险。鉴于目前肥胖症的流行，以及与年龄相关的痴呆症预期增加，即使这两种疾病之间存在适度的联系，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，进而影响脂肪和葡萄糖代谢、促炎细胞因子、氧化应激和内皮功能。脂肪细胞因子脂联素水平低与肥胖增加、高血压、血脂异常、胰岛素敏感性和2型糖尿病有关。这些发现表明，脂联素可能对痴呆症或认知能力下降具有保护作用，尽管这些联系尚不清楚。瘦素是一种脂肪细胞因子，也是由白色脂肪组织产生的，它调节能量平衡，动物模型表明，它也与学习和记忆有关，以及淀粉样β蛋白的沉积，淀粉样β蛋白是阿尔茨海默病神经纤维斑块的主要成分。这项建议是一项关于肥胖、脂肪细胞因子和认知衰退(包括全球和言语情景记忆)的前瞻性队列研究，研究对象是一名特征明确的拉美裔老年样本(N=1500)。这项提案的目标是研究整体肥胖、内脏肥胖、瘦素、脂联素与认知功能水平以及居住在社区的拉丁裔老年队列中认知能力下降之间的关系。我们假设：1)与不肥胖的人相比，那些肥胖的人将有更大的独立于糖尿病和心血管疾病的认知下降，2)内脏肥胖(腰围)的影响将比整体肥胖(根据身体质量指数估计)更大，2)高瘦素水平的人比低水平的人认知能力下降更大，3)低脂联素水平的人比高水平的人认知能力下降更大。我们还将探索这些脂肪细胞因子是否在肥胖的各种指标和认知之间起到中介作用。由于拉美裔人患糖尿病的风险更高，而且更有可能患有内脏肥胖症，这是一个重要的群体，可以用来表征脂肪细胞因子在认知和认知能力下降中的潜在作用。

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.