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

描述（由申请人提供）：有氧运动有望治疗认知障碍和改变阿尔茨海默病（AD）的脑萎缩。AD目前困扰着540万美国人，如果无法治愈，到2050年将影响1400万人。认知障碍是AD的标志性症状，并导致其他症状的表现，导致不良后果，包括生活质量低，早期机构化和高成本（2010年价值2026亿美元）。AD中的运动研究刚刚出现，并且在认知结果方面产生了相互矛盾的结果，主要是由于低剂量，有氧运动的不良表现以及缺乏控制。这项初步随机对照试验（RCT）将是第一个研究 为期6个月的新型、个体化、中等强度自行车干预对社区居住的轻度至中度AD老年人认知和海马体积的影响。两个互补的框架指导我们的研究：心血管健康假设，表明增加有氧健身改善认知;和生物机械论，通过确定的作用机制，解决了第一个框架的特异性缺乏。 有氧运动Yu博士（PI）是一名早期研究者，她成功地带领她的跨学科团队开发和执行了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。该先导性RCT将90例受试者随机分配至6个月自行车干预组或注意力控制（假运动）组，采用随机3例和6例受试者的排列区组，分配比例为2：1，并再随访6个月。将在基线、3、6、9和12个月时通过AD评估量表-认知（ADAS-Cog）测量认知。将在基线、6个月和12个月时通过磁共振成像（MRI）测量海马体积。样本量将为我们提供80%的把握度，以检测6个月时ADAS-Cog组内变化的至少2.5分差异。具体目标是：确定骑自行车干预对AD认知的直接影响。我们假设，在AD药物RCT中，干预受试者在6个月时ADAS-Cog的组内增幅小于安慰剂受试者，而在AD药物RCT中，对照受试者的增幅与安慰剂受试者相同。Aim II.检查骑自行车干预是否减缓了AD从基线到12个月的认知下降。我们预计，干预受试者在12个月内的ADAS-Cog增幅将小于对照受试者。目的III：使用MRI评估有氧运动对AD患者海马体积的影响超过12个月。我们预计，干预受试者将有一个较小的减少海马体积超过12个月比对照组。这项研究的广泛影响是解决有氧运动在AD治疗效果方面的知识缺口，并为AD提供潜在的有效治疗方法。这项试点研究将为未来的全面RCT提供信息，该RCT将解决我们的长期目标，即阐明有氧运动如何改变AD进展，并为未来的研究提供重要基础。

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.