Effects of Standardized Aerobic Exercise-Training on Neurocognitive and Neurodege

描述（由申请人提供）：本试验性研究的主要目的是确定患有轻度AD（AD）的非裔美国人（AA）是否可以入组并保留在为期6个月的有氧运动训练研究中。采用随机对照试验方法，我们将研究有氧运动训练对神经认知功能和大脑葡萄糖稳态的影响。目前尚不确定是否轻度AD的AA可以招募到这样的研究，也没有健身适应神经认知功能的关系进行了系统的检查，在这个人群中。除了评估干预效果的目标外，我们还将评估APOE与有氧健身引起的神经认知变化的差异关系。我们的长期目标是探索健身适应对神经认知产生影响的机制--值得注意的是，低水平的高密度脂蛋白胆固醇（HDL-C），升高的炎症（C-反应蛋白（CRP）和白细胞介素（IL-1A））、葡萄糖稳态紊乱、高血压和内皮功能障碍是小动脉硬化、脑灌注减少和缺氧的前体，所有这些都可能增加AD风险。由于许多这些推定的AD风险因素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风险降低中的作用。一个由神经影像学、神经病学、心理学、运动生理学、心脏病学和遗传学方面非常成功的专家组成的团队已经被召集来进行这项研究。在获得知情同意后，参与者将接受初步运动筛查，以确定他们安全运动的能力。将112名受试者随机分为干预组（n=56）和对照组（n=56）后，将进行基线神经心理学、神经影像学和生物标志物评价。干预组每周进行3次有监督的有氧运动训练，对照组每周进行3次伸展运动训练。在干预组完成6个月的有氧运动训练后，将在干预组和对照组中重复所有基线测试。将使用适当的多变量方法比较组间认知表现。这项拟议的工作有可能增加一个实际有效的策略，以延迟在最危险的人群中AD的进展。与我们的假设一致的结果将形成大规模临床试验的基础，以及有氧健身的处方，以预防或减轻与AD相关的身体，心理和经济负担。公共卫生相关性：这项试点研究的主要目的是确定轻度AD（AD）的非洲裔美国人（AA）是否可以参加并保留6个月的有氧运动训练。采用随机对照试验方法，我们将研究有氧运动训练对神经认知功能和大脑葡萄糖稳态的影响。首先，我们将评估APOE多态性与有氧健身引起的神经认知功能变化的差异关系。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。虽然抗胆碱酯酶治疗大大改善了AD的对症治疗，但尚未证明其可显著减缓疾病进展。AD的过度发病率和死亡率继续对家庭和美国产生巨大的经济负担。在显示出AD的最早症状的那些人中保持智力灵活性可以改善与该疾病相关的身体、情感和经济负担，并且这是一个重要的公共卫生目标。一种有前途的循证和相对无副作用的生活方式方法正在成为抗胆碱酯酶治疗的替代或辅助治疗。具体来说，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惊人地大，结果相当一致，但样本量很小，主要包括高加索人。重要的是，影响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公认的AD风险因素，如高密度脂蛋白胆固醇（HDL-C），炎症和小动脉硬化。然而，这些假定的风险因素的改善尚未被探索为有氧训练改善人类认知功能的潜在机制。鉴于AA：i）AD的发病率和患病率高于高加索人，ii）缺乏关于运动对认知功能有益影响的横断面数据，缺乏前瞻性数据; iii）相对于高加索人而言，更多久坐，数据显示运动的有益影响，因此有运动诱导风险改善的空间;老年AA的运动和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.