Cognitive/Brain Effects of Adding Weight Loss to Exercise in Obese Older Adults

描述（由申请人提供）：美国和世界各地的人口正在迅速老龄化-联合国估计，到2050年，老年人的人口将首次超过年轻人的人口。与此同时，肥胖正在迅速达到流行病的程度。世界卫生组织指出，自1980年以来，全球肥胖人数翻了一番，2008年有15亿成年人肥胖。老龄化和超重人口的结合对认知健康有严重影响，因为老龄化和肥胖都与认知能力下降有关，老龄化和肥胖增加的风险因素也是如此，如胰岛素抵抗和高血压。认知功能差是一个重要的公共卫生问题，特别是在老年人中，因为它可以降低个人进行日常生活活动或遵循规定的医疗保健活动的能力，导致机构化和丧失独立性。有充分的证据表明，有氧运动有益于老年人的认知功能。运动还可以改善血糖调节和胰岛素敏感性，并可能降低炎症，这些都是运动诱导认知改善的潜在机制。通过减少热量摄入来有意减轻体重比单独锻炼更能改善认知能力下降的代谢风险因素，这表明体重和脂肪的减少可能会增强锻炼的认知益处。然而，减肥对老年人是否安全和健康是一个有争议的问题，一些研究实际上表明，较高的体重与老年人更好的认知有关。因此，目前尚不清楚在有氧运动干预中加入热量限制是否会对肥胖老年人的认知、大脑结构和功能产生额外的益处。这项拟议中的研究通过调查肥胖老年人在运动中增加减肥的效果，作为一种潜在的减肥方法， 治疗老年人肥胖相关认知能力下降的途径。这项研究还为候选人提供了一个很好的培训途径，其总体职业目标是成为一名独立的临床和翻译研究人员。她在认知神经影像学方面的强大背景将通过临床试验研究和行为减肥干预的培训-新的分析技术-以及肥胖，痴呆和其他老年综合征的知识来增强。这项培训将使她能够设计新的试验，进一步研究代谢疾病的可改变风险因素与大脑和认知之间的关系。

DESCRIPTION (provided by applicant): The population in the US and worldwide is aging rapidly~ the United Nations estimates that by 2050, for the first time in history, the population f older people will exceed the population of younger people. At the same time, obesity is rapidly reaching epidemic proportions. The World Health Organization states that worldwide, obesity has doubled since 1980, and in 2008, 1.5 billion adults were obese. The combination of an aging, overweight population has serious implications for cognitive health, as aging and obesity are both associated with cognitive decline, as are risk factors that are increased by both aging and obesity, such as insulin resistance and hypertension. Poor cognitive function is a significant public health concern, particularly in older adults, because it can reduce an individual's ability o perform activities of daily living or follow prescribed health care activities, leads to increased institutionalization and loss of independence. There is good evidence that aerobic exercise benefits cognitive function in older adults. Exercise also improves glucose regulation and insulin sensitivity, and may lower inflammation, all potential mechanisms for exercise-induced improvement in cognition. Intentional weight loss through reduced caloric intake improves metabolic risk factors for cognitive decline more than exercise alone, suggesting that weight and fat loss may enhance the cognitive benefits of exercise. However, whether weight loss is safe and healthy for older adults is a matter of controversy, and some studies actually show that higher body weight is associated with better cognition in older adults. Thus, it is unknown whether adding caloric restriction to an aerobic exercise intervention provides an additive benefit on cognition, and brain structure and function, beyond exercise alone in obese older adults. The proposed study addresses concerns of national and worldwide health significance by investigating the effects of adding weight loss to exercise in obese older adults as a potential avenue for remediation of obesity-related cognitive decline in older adults. This study also provides an excellent avenue for training for the candidate, whose overall career goal is to become an independent clinical and translational researcher. Her strong background in cognitive neuroimaging of aging will be augmented by training in clinical trial research and behavioral weight loss interventions~ new analysis techniques~ and knowledge of obesity, dementia, and other geriatric syndromes. This training will allow her to design new trials that further investigate the relationships between modifiable risk factors for metabolic disease and the brain and cognition.