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)发病率的增加，促进健康大脑老化和预防阿尔茨海默病(AD)的战略变得越来越重要。动物数据表明，运动可能会改变AD小鼠模型的神经病理负担，而人类对正常衰老的研究表明，运动可能会保护大脑免受与年龄相关的功能和结构变化的影响。尽管有这些研究，但关于运动在AD中的作用的证据有限，需要严格、精心设计的试验来评估运动在AD中的益处。我们的总体假设是，增强有氧健身将减缓AD的进展。我们建议对早期阿尔茨海默病患者进行26周有氧运动与拉伸(对照组)的随机对照试验，以检验这一假设。运动训练将通过大堪萨斯城基督教青年会的本地网络在社区环境中进行，以我们集团由NIH资助的与基督教青年会网络合作的历史为基础。拟议的试点试验的总体目标是通知和推进后续全面临床试验的设计，与资金公告阿尔茨海默病试点临床试验(PAR-07-142)保持一致。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AD有氧健身的初步疗效数据，以及另外两个探索性目标，评估有氧健身与大脑健康有关的疾病修改益处和潜在机制。目标1将验证这样的假设，即增强的有氧健身将在AD的最早临床阶段为个人提供认知益处，而目标2将评估增强的有氧健身是否具有功能和行为益处。这些探索性的目的是1)改进评估运动对疾病改善效果的神经成像指标，2)检查潜在的潜在机制(如合成代谢和炎症标记物)，将健康与大脑健康联系起来。目前的项目是由KU阿尔茨海默氏症和记忆计划开发的一系列计划调查的自然延伸。这项试点临床试验将为随后的全面临床试验的设计提供信息，同时为探索有氧运动对AD早期临床阶段大脑健康的影响和潜在的潜在机制提供重要数据。需要有严格的数据来证明和定义锻炼对AD的疗效。这不仅将对鼓励公众适应更积极的生活方式的公共卫生政策产生影响，还将刺激为AD患者制定有效的运动交付计划。 公共卫生相关性：随着老年人口的空前增长和随后阿尔茨海默病患病率的增加，促进健康大脑老化和预防阿尔茨海默病(AD)的战略变得越来越重要。有必要进行严格的、精心设计的试验，以便更准确地确定运动在AD中的作用。展示和确定运动在AD中的有效性不仅将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，还将刺激为AD患者制定有效的运动交付计划。

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.