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

体力活动对 MCI 患者大脑功能和网络连接的影响

• 批准号: 9264956
• 负责人: Judy Pa
• 金额: $ 55.51万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9264956
• 关键词: Activities of Daily Living; Aerobic; Aerobic Exercise; Affect; Age-Years; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Biological Markers; Blood; Brain; Brain-Derived Neurotrophic Factor; Clinical; Clinical Trials; Clinical dementia rating scale; Cognition; Cognitive; Disease; Disease Progression; Early Intervention; Early treatment; Elderly; Exercise; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Health education; Hippocampus (Brain); Home environment; Hyperactive behavior; Impaired cognition; Impairment; Individual; Insulin-Like Growth Factor I; Intervention; Investments; MRI Scans; Maintenance; Maps; Measurement; Measures; Memory; Methodology; Methods; Modernization; Onset of illness; Outcome; Outcome Measure; Oxygen Consumption; Participant; Pathology; Patients; Pharmacology; Physical activity; Positron-Emission Tomography; Prefrontal Cortex; Process; Randomized; Randomized Controlled Trials; Recommendation; Recruitment Activity; Rest; Risk; Scanning; Serum; Signal Transduction; Somatostatin; Stretching; Surgeon; Testing; United States National Institutes of Health; Vulnerable Populations; Walking; active control; amnestic mild cognitive impairment; arm; base; brain dysfunction; brain health; brain volume; cerebral atrophy; cognitive function; cognitive performance; cognitive testing; design; donepezil; effective therapy; executive function; exercise intensity; exercise intervention; functional MRI scan; gamma-Aminobutyric Acid; improved; improved functioning; in vivo; insight; interdisciplinary approach; lifestyle factors; mild cognitive impairment; neurobiological mechanism; neuroimaging; novel strategies; post intervention; pre-clinical; primary outcome; public health intervention; public health relevance; relating to nervous system; remediation; secondary outcome; sedentary; sobriety; treadmill

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.

描述（由申请人提供）：这是修订后的申请NIH R01-AG046928-01，标题为“身体活动对MCI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老年痴呆症（AD）风险的久坐老年人早期脑功能损伤的影响。阿尔茨海默病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，在疾病过程的早期开始治疗，并探索非药物干预措施。体育活动最近被认为是延缓疾病发作和减缓阿尔茨海默病认知能力下降的一种有希望的干预措施。然而，在轻度认知障碍（MCI）的高危老年人中，体育活动对神经生物学作用机制的影响，如大脑活动和网络功能