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

描述（由申请人提供）：这是修订后的申请NIH R 01-AG 046928 -01，标题为“身体活动对MCI患者脑功能和网络连接的影响”。“该项目的总体目标是评估身体活动对治疗有阿尔茨海默病（AD）风险的久坐老年人大脑功能早期损伤的影响。AD是老年人认知障碍的最常见原因。对有效治疗的需求已变得势在必行，因为全世界有3 600万人受到影响，而且人数还在增加。几项大型药理学试验的结果令人清醒，缺乏显著的临床结果，促使范式转变，在疾病过程中更早地开始治疗，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，用于延迟AD的疾病发作和减缓认知能力下降。然而，体力活动对神经生物学作用机制的影响，如轻度认知障碍（MCI）高危老年人的大脑活动和网络功能， AD的临床前阶段，仍然在很大程度上未被探索。因此，有必要进行设计良好的随机对照试验（RCT），以检查这一弱势群体的身体活动干预的功能性脑健康结果。本提案的目的是评估身体活动作为改善功能性脑健康的干预措施，通过补救海马功能障碍和增强MCI的功能网络连接。在随机对照试验中使用现代神经科学方法的独特跨学科方法，将对一组全面的结局进行评价。该项目将招募90名年龄在50-85岁之间的患有遗忘型MCI的久坐参与者。根据当前外科医生关于中等强度运动的建议，参与者将被随机分配到三个家庭组中的一个，为期6个月的干预期：1）每周150分钟的有氧步行，2）每周150分钟的拉伸主动控制，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的影响，前额叶皮层和海马之间的功能连接，以及默认模式和执行网络的内在连接。此外，我们还将检查与体力活动相关的脑容量、认知、功能和血清生物标志物的次要结果。将使用淀粉样蛋白PET检查局部AD病理学对结局指标变化的影响。

DESCRIPTION (provided by applicant): 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 th 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.