Effects of Standardized Aerobic Exercise-Training on Neurocognitive and Neurodege

描述(由申请人提供)：这项初步研究的主要目的是确定患有轻度AD(AD)的非裔美国人(AA)是否可以被纳入并保留在为期6个月的有氧运动训练研究中。采用随机对照试验方法，研究有氧运动训练对神经认知功能和脑葡萄糖稳态的影响。目前还没有确定轻度AD的AA是否可以被招募到这样的研究中，也没有系统地研究适应与神经认知功能的关系。除了评估干预效果的目标外，我们还将评估载脂蛋白E与有氧健身引起的神经认知变化的区别关系。我们的长期目标是探索健身适应影响神经认知的机制--特别是低水平的高密度脂蛋白胆固醇(HDLC)、炎症(C反应蛋白(CRP)和白介素A(IL-1a))升高、血糖稳态失调、高血压和内皮功能障碍是动脉硬化、脑血流减少和缺氧的先兆，所有这些都可能增加AD的风险。由于这些假定的AD危险因素中的许多都容易受到生活方式改变的影响，我们还将评估它们在有氧健身相关的认知功能改善和AD风险降低方面的作用。一个由神经成像、神经学、心理学、运动生理学、心脏病学和遗传学领域的非常成功的专家组成的团队已经组成了一个团队来进行这项研究。在获得知情同意后，参与者将接受初步的运动筛查，以确定他们安全运动的能力。在将112名参与者随机分为干预组(n=56)和对照组(n=56)后，将进行基线神经心理学、神经成像和生物标记物评估。干预组每周进行3次有监督有氧运动训练，对照组每周进行3次伸展运动。在干预组完成为期6个月的有氧运动训练后，干预组和对照组都将重复所有的基线测试。不同组之间的认知表现将使用适当的多变量方法进行比较。这项拟议的工作有可能增加一种实用有效的策略来延缓高危人群中AD的进展。符合我们假设的结果将成为大规模临床试验的基础，并为制定有氧健身处方以预防或减轻与AD相关的身体、心理和经济负担奠定基础。公共卫生相关性：这项初步研究的主要目的是确定患有轻度阿尔茨海默病(AD)的非裔美国人(AA)是否可以参加并保留在为期6个月的有氧运动训练中。采用随机对照试验方法，研究有氧运动训练对神经认知功能和脑葡萄糖稳态的影响。初步评估载脂蛋白E基因多态性与有氧运动引起的神经认知功能改变之间的差异关系。我们的长期目标是研究健身适应对神经认知功能产生影响的机制。虽然抗胆碱酯酶疗法极大地改善了AD的对症治疗，但尚未证明它们能显著减缓疾病的进展。阿尔茨海默病的过度发病率和死亡率继续给家庭和美国造成巨大的经济负担。在出现阿尔茨海默病最早症状的人中保持智力灵敏可能会减轻与疾病相关的身体、情感和经济负担，这是一个重要的公共卫生目标。一种有希望的循证和相对无副作用的生活方式正在成为抗胆碱酯酶疗法的替代或辅助疗法。具体地说，有氧运动训练已被证明可以改善认知功能。尽管这些研究的效应量令人惊讶地大，而且结果相当一致，然而，样本量很小，并且主要包括高加索人。重要的是，一种效应发生的机制尚未得到系统的证实。值得注意的是，有氧健身可以改善许多可能的AD危险因素，如高密度脂蛋白胆固醇(HDL-C)、炎症和动脉硬化。然而，这些假定的危险因素的改善还没有被探索为有氧训练改善人类认知功能的潜在机制。鉴于AAS：i)AD的发病率和患病率高于高加索人，ii)缺乏横断面数据，并且缺乏运动对认知功能有益影响的前瞻性数据；iii)相对于高加索人，他们更久坐不动，数据显示运动的有益效果，因此有可能通过运动来改善风险；在老年AA中开展运动与认知的随机对照试验势在必行。

DESCRIPTION (provided by applicant): The primary purpose of this pilot study is to determine whether African Americans (AA) with mild AD (AD) can be enrolled and retained in a 6-month aerobic exercise-training study. Using a randomized controlled trial approach, we will examine the effects of aerobic exercise-training on neurocognitive function, and on cerebral glucose homeostasis. It is yet to be determined whether AAs with mild AD can be recruited into such a study, nor has the relationship of fitness adaptation to neurocognitive function been systematically examined in this population. In addition to the goal of assessing the intervention effects, we will evaluate the differential relationships of APOE to aerobic fitness-induced changes in neurocognition. Our long-term goal is to explore the mechanism by which fitness adaptation exerts an effect on neurocognition -- Notably, low levels of high-density lipoprotein cholesterol (HDL-C), elevated inflammation (C-reactive protein (CRP) and interleukins (IL-1A)), deranged glucose homeostasis, hypertension and endothelia dysfunction are precursors of arteriolosclerosis, decreased cerebral perfusion and oxygen deprivation, all of which may increase AD risk. Because many of these putative AD risk factors are susceptible to lifestyle alterations, we will also assess their roles in aerobic fitness-related improvements in cognitive function and reduction in AD risk. A team of highly successful experts in neuroimaging, neurology, psychology, exercise physiology, cardiology and genetics has been assembled to conduct this study. After obtaining informed consent, participants will undergo initial exercise screening to determine their ability to exercise safely. Following randomization of 112 participants into intervention (n=56) and control (n=56) groups, baseline neuropsychological, neuroimaging and biomarker evaluations will be performed. The intervention group will undergo 3 times/week supervised aerobic exercise-training, while the control group undergoes stretch exercise 3 times/week. At the completion of a 6-month aerobic exercise-training by the intervention group, all baseline tests will be repeated in both the intervention and control groups. Between groups cognitive performance will be compared using appropriate multivariate methods. This proposed work has the potential to add a practical effective strategy to delay progression of AD in populations at most risk. Results consistent with our hypotheses will form the basis for large-scale clinical trials, and the prescription of aerobic fitness to prevent or attenuate the physical, psychological and the economic burden associated with AD. PUBLIC HEALTH RELEVANCE: The primary purpose of this pilot study is to determine whether African Americans (AA) with mild AD (AD) can be enrolled and retained in a 6-month aerobic exercise-training. Using a randomized controlled trial approach, we will examine the effects of aerobic exercise-training on neurocognitive function, and on cerebral glucose homeostasis. Preliminarily, we will evaluate the differential relationships of APOE polymorphism to aerobic fitness-induced changes in neurocognitive function. Our long-term goal is to examine the mechanisms by which fitness adaptation exert an effect on neurocognitive function. Although anticholinesterase therapies have greatly improved symptomatic treatment of AD, they have not been demonstrated to significantly slow disease progression. Excess morbidity and mortality from AD continue to generate an enormous economic burden on families and on the United States. Preservation of intellectual dexterity among those showing earliest symptoms of AD may ameliorate the physical, emotional, and economic burden associated with the disease, and that, is an important public health goal. A promising evidence-based and relatively side-effect free lifestyle approach is emerging as an alternative or adjunct to anticholinesterase therapy. Specifically, aerobic exercise-training has been demonstrated to improve cognitive function. Though, the effect size for these studies is surprisingly large, and the results fairly consistent, however, the sample sizes were small and included mostly Caucasians. Importantly, the mechanism by which an effect occurs is yet to be systematically substantiated. Remarkably, aerobic fitness can improve many of the putative AD risk factors such as high-density lipoprotein cholesterol (HDL-C), inflammation, and arteriolosclerosis. However, improvements in these putative risk factors have not been explored as potential mechanisms by which aerobic training improves cognitive function in humans. Given that AAs: i) have higher incidence and prevalence of AD than Caucasians, ii) have paucity of cross-sectional, and lack prospective data on the beneficial effect of exercise on cognitive function; iii) are more sedentary relative to Caucasians, in whom data show the beneficial effect of exercise, and therefore have room for exercise-induced improvements in risk; a randomized controlled trial of exercise and cognition in older AAs is imperative.