Aerobic Exercise in Alzheimer's Disease: Cognition and Hippocampal Volume Effects

描述(申请人提供)：有氧运动有望治疗阿尔茨海默病(AD)的认知障碍和改变脑萎缩。AD目前困扰着540万美国人，如果找不到治愈方法，到2050年将影响1400万人。认知障碍是阿尔茨海默病的标志性症状，也是导致不良结局的其他症状的表现，包括低生活质量、早期住院和高昂的费用(2010年的估值为2026亿美元)。AD的运动研究才刚刚出现，在认知结果方面产生了相互矛盾的发现，这主要是由于低剂量、糟糕的有氧运动以及缺乏控制。这项试点随机对照试验(RCT)将是第一个研究 一种新的为期6个月、个性化、中等强度的骑行干预对社区居住的轻至中度阿尔茨海默病老年人认知和海马体体积的影响。两个互补的框架指导我们的研究：心血管健康假说，认为增加有氧适应可以改善认知；生物机制理论，通过确定 有氧运动。Yu博士(Pi)是一名早期研究员，她成功地带领她的跨学科团队开发并实施了为期6个月的自行车干预，建立了招募、保留和坚持的可行性，并通过3项前测后测研究显示了积极的认知结果。这项试验性随机对照试验将90名受试者随机分为6个月的骑车干预组或注意力控制组(假运动)，随机使用3名和6名受试者的排列区块，分配比例为2：1，并对他们进行另外6个月的跟踪调查。在基线、3个月、6个月、9个月和12个月时用AD评定量表(ADAS-Cog)测量认知能力。在基线、6个月和12个月时用磁共振成像(MRI)测量海马体体积。样本量将使我们有80%的能力来检测6个月后ADAS-Cog组内变化至少2.5个点的差异。具体目标为：目的一、确定自行车运动干预对阿尔茨海默病患者认知的即时影响。我们假设，在6个月时，在AD药物RCT中，干预受试者的ADAS-Cog在组内的增加将比安慰剂受试者小，而在AD药物RCT中，对照组受试者将与安慰剂组受试者有相同的增加。目的II.检查骑车干预是否将AD患者的认知功能下降从基线减缓到12个月。我们预计，在12个月内，干预受试者的ADAS-Cog增加幅度将小于对照受试者。目的：应用磁共振成像技术评价有氧运动对12个月以上AD大鼠海马区体积的影响。我们预计，在12个月内，干预受试者的海马体体积将比对照受试者有较小的减少。这项研究的广泛影响是解决有氧运动对阿尔茨海默病治疗效果的关键认识差距，并提供一种潜在的有效治疗阿尔茨海默病的方法。这项初步研究将为未来的全面随机对照试验提供信息，这将解决我们的长期目标，即阐明有氧运动如何改变AD的进展，并为未来的研究提供重要的基础。

DESCRIPTION (provided by applicant): Aerobic exercise holds promise for treating cognitive impairment and altering brain atrophy in Alzheimer's disease (AD). AD currently afflicts 5.4 million Americans and will affect 14 million by 2050 if no cure is found. Cognitive impairment is the hallmark symptom of AD and contributes to the manifestation of other symptoms that result in poor outcomes, including low quality of life, early institutionalization, and high costs (valuedat $202.6 billion in 2010). Exercise studies in AD are just emerging and have produced conflicting findings on cognitive outcomes, largely due to low doses, poor delivery of aerobic exercise, and lack of controls. This pilot randomized controlled trial (RCT) will be the first to investigate the effects of a novel 6-month, individualized, moderate-intensity cycling intervention on cognition and hippocampal volume in community-dwelling older adults with mild-to-moderate AD. Two complementary frameworks guide our study: the cardiovascular fitness hypothesis that suggests increased aerobic fitness improves cognition; and the biological mechanistic theory which addresses the lack of specificity of the first framework by identifying the mechanisms of action of aerobic exercise. Dr. Yu (PI), an Early-Stage Investigator, has successfully led her interdisciplinary team to develop and execute the 6-month cycling intervention, establish the feasibility of recruitment, retention, and adherence, and show positive cognitive results via 3 pretest posttest studies. This pilot RCT will randomize 90 subjects to the 6-month cycling intervention or attention control (sham exercise) groups using permuted blocks of 3 and 6 subjects randomly and a 2:1 allocation ratio, and follow them for another 6 months. Cognition will be measured by the AD Assessment Scale-Cognition (ADAS-Cog) at baseline, 3, 6, 9, and 12 months. Hippocampal volume will be measured by magnetic resonance imaging (MRI) at baseline, 6, and 12 months. The sample size will give us 80% power to detect at least a 2.5-point difference in within-group changes in ADAS-Cog at 6 months. The specific aims are: Aim I. Determine the immediate effect of the cycling intervention on cognition in AD. We hypothesize that intervention subjects will have a smaller within-group increase in ADAS-Cog at 6 months than placebo subjects in AD drug RCTs, while control subjects will have the same increase as placebo subjects in AD drug RCTs. Aim II. Examine if the cycling intervention slows cognitive decline in AD from baseline to 12 months. We expect that intervention subjects will show a smaller increase in ADAS-Cog over 12 months than control subjects. Aim III: Assess the effect of aerobic exercise on hippocampal volume in AD over 12 months using MRI. We expect that intervention subjects will have a smaller decrease in hippocampal volume over 12 months than control subjects. The study's broad impacts are to address the critical gap in knowledge of the therapeutic effects of aerobic exercise in AD and offer a potentially effective treatment for AD. This pilot study will inform a future full-scale RCT that will address our long-term goal of elucidating how aerobic exercise alters AD progression and provide important foundations for future research.