Aerobic Fitness in Slowing the Progression of Alzheimer's Disease

描述（由申请人提供）：随着阿尔茨海默病（AD）的日益流行，促进大脑健康老化和预防AD的策略变得越来越重要。动物数据表明，运动可以改变阿尔茨海默病小鼠模型的神经病理负担，而对正常衰老的人类研究表明，运动可以防止与年龄相关的功能和结构的大脑变化。尽管有这些研究，关于运动在阿尔茨海默病中的作用的证据有限，需要严格的、精心设计的试验来评估运动对阿尔茨海默病的益处。我们的总体假设是，增强有氧适应度将减缓AD的进展。我们建议对早期AD患者进行为期26周的有氧运动和伸展运动（对照组）的随机对照试验来检验这一假设。运动训练将通过大堪萨斯城基督教青年会的当地网络在社区环境中进行，建立在我们集团与美国国立卫生研究院资助的基督教青年会网络合作的历史基础上。拟议试点试验的总体目标是告知和推进后续全规模临床试验的设计，与资助公告阿尔茨海默病试点临床试验（PAR-07- 142）一致。我们将通过两个主要目标来实现这一目标，这两个主要目标旨在产生阿尔茨海默病有氧健身的初步疗效数据，另外两个探索性目标是评估有氧健身与大脑健康相关的疾病改善益处和潜在机制。目的1将检验增强有氧适能是否会对阿尔茨海默病早期临床阶段的个体提供认知益处的假设，而目的2将评估增强有氧适能是否具有功能和行为益处。探索性目标旨在1)完善评估运动改善疾病效果的神经影像学措施，2)检查与大脑健康相关的潜在潜在机制（如合成代谢和炎症标志物）。目前的项目是由堪萨斯大学阿尔茨海默病和记忆项目开发的程序化研究线的自然延伸。这项试点临床试验将为后续全面临床试验的设计提供信息和推进，同时为探索有氧运动对阿尔茨海默病早期临床阶段大脑健康的影响及其潜在机制提供重要数据。需要严谨的数据来证明和定义运动对阿尔茨海默病的疗效。这不仅会对公共卫生政策产生影响，鼓励公众适应更积极的生活方式，还会刺激为AD患者制定有效的锻炼计划。

DESCRIPTION (provided by applicant): Strategies for promoting healthy brain aging and preventing Alzheimer's disease (AD) are increasingly important with the increasing prevalence of AD. Animal data suggests exercise may modify the AD neuropathological burden in mouse models of the disease while human studies of normal aging suggest exercise may protect against age-related functional and structural brain changes. Despite these studies, limited evidence exists on the role of exercise in AD and there is a need for rigorous, well-designed trials to assess the benefits of exercise in AD. Our overall hypothesis is that enhanced aerobic fitness will slow the progression of AD. We propose to examine this hypothesis in a randomized, controlled trial of 26 weeks of aerobic exercise vs. stretching (control group) in individuals with early-stage AD. Exercise training will occur in a community setting through the local network of Greater Kansas City YMCAs, building on our group's history of NIH-funded collaborations with the YMCA network. The overall objective of the proposed pilot trial is to inform and advance the design of a subsequent full- scale clinical trial, consistent with the funding announcement Alzheimer's Disease Pilot Clinical Trials (PAR-07- 142). We will meet this objective through two primary aims designed to generate preliminary efficacy data on aerobic fitness in AD and two additional exploratory aims assessing disease-modifying benefits and potential mechanisms relating aerobic fitness with brain health. Aim 1 will test the hypothesis that enhanced aerobic fitness will provide cognitive benefits to individuals in the earliest clinical stages of AD while aim 2 will assess whether enhanced aerobic fitness has functional and behavioral benefits. The exploratory aims are designed to 1) refine neuroimaging measures assessing disease-modifying effects of exercise and, 2) examine potential underlying mechanisms (such as anabolic and inflammatory markers) relating fitness with brain health. The current project is a natural extension of a programmatic line of investigation developed by the KU Alzheimer and Memory Program. This pilot clinical trial will inform and advance the design of a subsequent full scale clinical trial while providing important data to explore the effect, and potential underlying mechanisms, of aerobic exercise on brain health in the earliest clinical stages of AD. There is a need for rigorous data demonstrating and defining the efficacy of exercise in AD. This would not only have an impact on public health policy in encouraging the public to adapt more active lifestyles, it would also stimulate the development of effective exercise delivery programs for individuals with AD. PUBLIC HEALTH RELEVANCE: Strategies for promoting healthy brain aging and preventing Alzheimer's disease (AD) are increasingly important with the unprecedented growth of the elderly population and subsequent increase in the prevalence of AD. There is a need for rigorous, well-designed trials to more precisely define the role of exercise in AD. Demonstrating and defining the efficacy of exercise in AD would not only have an impact on public health policy in encouraging the public to adapt more active lifestyles, it would also stimulate the development of effective exercise delivery programs for individuals with AD.