Effect of Aerobic Exercise on Alzheimer's Pathophysiology in Preclinical AD

描述（由申请人提供）：随着老年人口的空前增长，促进健康脑老化和预防阿尔茨海默病（AD）的策略越来越重要。淀粉样蛋白成像技术的出现为在假定的疾病早期阶段识别个体创造了机会。大约30%的认知正常的老年人患有脑淀粉样变性并符合“临床前AD”的研究标准。本研究旨在探讨有氧运动对AD病理生理学（淀粉样蛋白负荷）和相关的“下游”神经变性（局部萎缩）以及临床前AD认知功能下降的影响。我们的长期研究目标是开发和测试预防AD的策略。我们将在100名临床前AD患者中检查52周有氧运动计划的效果。堪萨斯大学阿尔茨海默病中心（KU ADC; P30 AG 035982）将使用Florbetapir PET成像筛选400名65岁及以上久坐、认知正常（CDR 0）的个体，以招募100名临床前AD参与者参加运动试验。受试者将以2：1的比例随机分配至有氧运动组（n=67）和拉伸/调理对照组（n=33）。运动训练将通过大堪萨斯城基督教青年会网络在社区环境中进行，建立在我们与基督教青年会合作的NIH资助的历史基础上。我们假设，52周的有氧运动将与Florbetapir PET成像测量的较低淀粉样蛋白负荷（目的1），减轻海马萎缩（目的2），并提供认知益处（目的3）相关。动物数据表明，运动可以改变AD神经病理学负担，而人类研究表明，运动可以防止与年龄相关的功能和结构性大脑变化。然而，目前的数据不足以得出结论， 体育锻炼可以延缓或预防AD，因此仍然迫切需要进行严格的干预试验来研究AD的预防策略。该提案将提供重要的初步数据，评估运动对高危个体AD病理生理学的疾病修饰益处，并为设计更明确的运动作为AD预防策略的研究提供信息。

DESCRIPTION (provided by applicant): Strategies for promoting healthy brain aging and preventing Alzheimer's disease (AD) are increasingly important with the unprecedented growth of the elderly population. The advent of amyloid imaging has created an opportunity to identify individuals in the putative earliest stages of the disease. Approximately 30% of cognitively normal older adults have cerebral amyloidosis and meet research criteria for "preclinical AD." This proposal examines the effects of aerobic exercise on AD pathophysiology (amyloid burden) and associated "downstream" neurodegeneration (regional atrophy) and cognitive decline in preclinical AD. Our long-term research goal is to develop and test strategies to prevent AD. We will examine the effects of a 52-week aerobic exercise program in 100 individuals with preclinical AD. The University of Kansas Alzheimer's Disease Center (KU ADC; P30AG035982) will screen 400 sedentary, cognitively normal (CDR 0) individuals age 65 and older with Florbetapir PET imaging to enroll 100 preclinical AD participants into the exercise trial. Participants will be randomized in a 2:1 ratio to either aerobic exercise (n=67) vs. stretching / toning control (n=33). Exercise training will occur in a community setting through the network of Greater Kansas City YMCAs, building on our history of NIH-funded collaborations with the YMCA. We hypothesize that 52 weeks of aerobic exercise will be associated with lower amyloid burden as measured by Florbetapir PET imaging (aim 1), attenuate hippocampal atrophy (aim 2), and provide cognitive benefits (aim 3). Animal data suggests exercise may modify AD neuropathological burden while human studies suggest exercise protects against age-related functional and structural brain changes. Nevertheless, the current data is insufficient to conclude that physical exercise delays or prevents AD and there remains a critical need for rigorous intervention trials to investigate AD prevention strategies. This proposal will provide important preliminary data assessing disease-modifying benefits of exercise on AD pathophysiology in high-risk individuals and inform the design of more definitive studies of exercise as an AD prevention strategy.