Effects of physical activity on brain function and network connectivity in MCI

项目摘要 这是修订后的申请NIH R 01-AG 046928 -01，标题为“身体活动对大脑功能的影响， MCI中的网络连接。”该项目的总体目标是评估身体活动对 治疗有患阿尔茨海默病（AD）风险的久坐老年人的脑功能早期损伤。 AD是老年人认知障碍的最常见原因。对有效治疗的需求 由于全世界有3 600万人受到影响，而且人数还在不断增加，结果从几个大的 药理学试验一直在清醒地认识到缺乏显着的临床结果，促使一个范例， 在疾病过程中更早开始治疗，并探索非药物干预措施。 身体活动最近已成为一种有希望的干预措施，可以延缓疾病的发作， 认知能力下降然而，体力活动对神经生物学作用机制的影响，如 作为轻度认知障碍（MCI）高危老年人的大脑活动和网络功能， AD的阶段，仍然在很大程度上未被探索。因此，需要设计良好的随机对照试验 (RCT)检查身体活动干预对这一弱势群体的功能性大脑健康的影响。 这项建议的目的是评估身体活动作为改善大脑功能的干预措施 通过修复海马功能障碍和增强MCI中的功能网络连接来改善健康。使用 RCT中现代神经科学方法的独特跨学科方法，一套全面的 将对结果进行评价。该项目将招募90名年龄在50-85岁之间的久坐参与者， 健忘型MCI与目前卫生部长关于中等强度运动的建议一致， 参与者将被随机分配到三个以家庭为基础的小组之一，为期6个月的干预期：1） 每周有氧步行150分钟; 2）主动控制拉伸运动150分钟; 3）健康教育 非主动控制，每组30名参与者。我们将研究体力活动对 海马区域BOLD活动的主要神经影像学结果， 前额叶皮层和海马体，以及默认模式和执行网络的内在连接。 此外，我们还将检查脑容量、认知、功能和血清生物标志物的次要结局 与身体活动有关。局部AD病理学对结果指标变化的影响将 使用淀粉样蛋白PET进行检查。

Project Summary This is the revised application NIH R01-AG046928-01, titled “Effects of physical activity on brain function and network connectivity in MCI.” The overall goal of this project is to assess the effect of physical activity on remediating early impairments in brain function in sedentary older adults at risk for Alzheimer's disease (AD). AD is the most common cause of cognitive impairment in older adults. The need for effective treatments has become imperative, as 36 million people worldwide are affected and counting. The results from several large pharmacological trials have been sobering with a lack of significant clinical outcomes, prompting a paradigm shift to initiate treatment earlier in the disease process and explore non-pharmacological interventions. Physical activity has recently emerged as a promising intervention for delaying disease onset and slowing cognitive decline in AD. However, the effect of physical activity on neurobiological mechanisms of action, such as brain activity and network function in at risk older adults with mild cognitive impairment (MCI), a preclinical stage of AD, remains largely unexplored. Thus, there is a need for well designed randomized controlled trials (RCT) examining functional brain health outcomes of physical activity intervention in this vulnerable population. The objective of this proposal is to evaluate physical activity as an intervention for improving functional brain health by remediating hippocampal dysfunction and enhancing functional network connectivity in MCI. Using a unique interdisciplinary approach of modern neuroscientific methodology in an RCT, a comprehensive set of outcomes will be evaluated. This project will recruit 90 sedentary participants between 50-85 years of age with amnestic MCI. Consistent with the current Surgeon General's recommendation on moderate-intensity exercise, participants will be randomly assigned to one of three home-based groups for a 6-month intervention period: 1) aerobic walking for 150 mins/week, 2) stretching active-control for 150 mins/week, and 3) health education non-active control, with 30 participants in each group. We will examine the effects of physical activity on the primary neuroimaging outcomes of regional BOLD activity in the hippocampal, functional connectivity between the prefrontal cortex and hippocampus, and intrinsic connectivity of the default mode and executive networks. Additionally, we will examine secondary outcomes of brain volume, cognition, function, and serum biomarkers associated with physical activity. The effect of regional AD pathology on change in the outcome measures will be examined using amyloid PET.