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 R01-AG046928-01，标题为“MCI中体力活动对脑功能和网络连接的影响”。该项目的总体目标是评估体育活动对修复久坐不动的阿尔茨海默病(AD)风险老年人早期脑功能损害的影响。AD是老年人认知障碍的最常见原因。由于全世界有3600万人受到影响，而且人数还在增加，因此对有效治疗的需求已成为当务之急。几个大型药理学试验的结果令人警醒，缺乏重大的临床结果，促使范式转变，在疾病过程中更早开始治疗，并探索非药物干预。最近，体力活动被认为是一种有希望的干预措施，可以延缓AD的发病和减缓认知能力的下降。然而，体力活动对患有轻度认知障碍(MCI)的高危老年人的神经生物学作用机制的影响，如大脑活动和网络功能，a 阿尔茨海默病的临床前阶段，在很大程度上仍未被探索。因此，需要设计良好的随机对照试验(RCT)来检验在这一脆弱人群中体力活动干预对脑功能健康的影响。这项建议的目的是评估体育活动作为一种干预措施，通过修复海马区功能障碍和增强MCI患者的功能网络连接来改善功能性脑健康。在随机对照试验中使用现代神经科学方法论的独特跨学科方法，将对一套全面的结果进行评估。该项目将招募90名50-85岁的健忘型MCI久坐参与者。根据目前卫生局局长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)有氧步行150分钟/周，2)伸展主动对照150分钟/周，3)健康教育非主动对照，每组30人。我们将研究身体活动对初级神经成像结果的影响，这些结果包括海马区局部BOLD活动、前额叶皮质和海马区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，我们将检查脑体积、认知、功能和与体力活动相关的血清生物标记物的次要结果。将使用淀粉样蛋白PET检查局部AD病理对预后指标变化的影响。

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.