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

描述（由申请人提供）：有氧运动有望治疗阿尔茨海默病（AD）的认知障碍和改变脑萎缩。阿尔茨海默病目前折磨着540万美国人，如果找不到治疗方法，到2050年将有1400万人受到影响。认知障碍是阿尔茨海默病的标志性症状，并导致其他症状的表现，导致预后不良，包括生活质量低、过早入院和高费用（2010年价值2026亿美元）。阿尔茨海默病的运动研究刚刚兴起，在认知结果方面产生了相互矛盾的发现，主要是由于低剂量、有氧运动的不良传递和缺乏控制。该试点随机对照试验（RCT）将是第一个调查

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.