Mild Cognitive Impairment: Cerebrovascular Dysfunction and Exercise Training

轻度认知障碍：脑血管功能障碍与运动训练

• 批准号: 8108170
• 负责人: RONG ZHANG
• 金额: $ 42.39万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8108170
• 关键词: Aerobic Exercise; Affect; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Animal Model; Balance training; Biological Markers; Blood; Blood Vessels; Brain; Cerebrospinal Fluid; Cessation of life; Chronic; Clinical Trials Design; Cognitive; Complement; Control Groups; Disease Progression; Economic Burden; Elderly; Encephalitis; Enrollment; Environmental Risk Factor; Enzyme-Linked Immunosorbent Assay; Exercise; Functional disorder; Funding; Genes; Goals; Grant; Health; Health Priorities; Homeostasis; Image; Immunoassay; Impaired cognition; Inflammation; Inflammatory; Interleukin-12; Interleukin-6; Intervention; Lead; Lesion; Ligands; Magnetic Resonance Imaging; Measures; Mediating; Metabolism; Methods; Neurofibrillary Tangles; Neuronal Dysfunction; Outcome; Outcome Study; Patients; Perfusion; Physical activity; Plasma; Positron-Emission Tomography; Preventive Intervention; Randomized; Randomized Controlled Clinical Trials; Research; Science; Senile Plaques; Signal Pathway; Societies; Spin Labels; Staging; Structure; Synapses; TNF gene; Techniques; Technology; Testing; Time; Training; Transgenic Animals; United States National Institutes of Health; Vasomotor; aging population; amyloid imaging; cerebral atrophy; cerebrovascular; cognitive function; cost; effective intervention; effective therapy; improved; mild neurocognitive impairment; mutant; neuroimaging; normal aging; novel; parent grant; presenilin; presenilin-1; prevent; symposium; tau Proteins; tau-1; white matter

DESCRIPTION (provided by applicant): Maintaining cognitive vitality with aging and reducing the risks for Alzheimer's disease (AD) are urgent national health priorities. The goal of this revision is to strengthen the currently funded grant "Mild cognitive impairment: cerebrovascular dysfunction and exercise training" (R01 AG033106) to determine whether aerobic exercise training reduces brain amyloid burden and ameliorates chronic brain inflammation in patients with mild cognitive impairment (MCI) - a transitional stage between normal aging and AD. We will accomplish the following specific aims. Aim 1: To determine whether exercise training reduces brain amyloid burden in patients with MCI. Brain amyloid burden in patients with MCI before and after one year of aerobic exercise training will be measured with positron emission tomography (PET) amyloid imaging using 18F-AV-45 and immunoassay (ELISA) of cerebral spinal fluid (CSF) levels of A2, tau and phosphorylated tau. Aim 2: To determine whether exercise training ameliorates chronic brain inflammation in patients with MCI. Chronic brain inflammation in patients with MCI will be assessed using quantitative multiplex immunoassay methods to measure plasma and CSF levels of inflammatory biomarkers such as TNF-1, IL-12, and IL-6. Aim 3: To determine whether reductions in brain amyloid burden and/or inflammation are correlated with improvement in brain perfusion. Brain perfusion will be measured using non-invasive transcranial Doppler and perfusion MRI (via arterial spin labeling techniques). Together with the parent grant, we also will determine whether these changes in neuroimaging and inflammatory biomarkers are correlated with changes in cognitive function. Understanding the underlying mechanisms by which exercise improves brain health is essential for developing effective interventions to maintain cognitive vitality with aging and to prevent or slow Alzheimer's disease. PUBLIC HEALTH RELEVANCE: Maintaining cognitive vitality with aging and reducing the risks for Alzheimer's disease (AD) are urgent national health priorities. The goal of this study is to understand the underlying mechanisms by which exercise preserves or improves cognitive function in patients with mild cognitive impairment (MCI) - a transitional stage between normal aging and AD. The outcome of this study is potentially important for developing effective interventions to prevent or slow Alzheimer's disease.

描述（由申请人提供）：随着年龄的增长保持认知活力和降低阿尔茨海默病（AD）的风险是国家健康的当务之急。此次修订的目的是加强目前资助的赠款“轻度认知障碍：脑血管功能障碍和运动训练”（R 01 AG 033106），以确定有氧运动训练是否减少轻度认知障碍（MCI）患者的脑淀粉样蛋白负担并改善慢性脑炎症-正常衰老和AD之间的过渡阶段。我们将实现以下具体目标。目的1：确定运动训练是否减少MCI患者的脑淀粉样蛋白负荷。将使用18F-AV-45和A2、tau和磷酸化tau的脑脊液（CSF）水平的免疫测定（ELISA），通过正电子发射断层扫描（PET）淀粉样蛋白成像来测量MCI患者在一年有氧运动训练之前和之后的脑淀粉样蛋白负荷。目的2：确定运动训练是否改善MCI患者的慢性脑炎症。将使用定量多重免疫测定方法评估MCI患者的慢性脑炎症，以测量炎症生物标志物（如TNF-1、IL-12和IL-6）的血浆和CSF水平。目的3：确定脑淀粉样蛋白负荷和/或炎症的减少是否与脑灌注的改善相关。将使用无创经颅多普勒和灌注MRI（通过动脉自旋标记技术）测量脑灌注。与父母资助一起，我们还将确定神经影像学和炎症生物标志物的这些变化是否与认知功能的变化相关。了解运动改善大脑健康的潜在机制对于开发有效的干预措施以保持认知活力并预防或减缓阿尔茨海默病至关重要。 公共卫生相关性：随着衰老保持认知活力并降低阿尔茨海默病（AD）的风险是国家卫生的紧迫优先事项。本研究的目的是了解运动保护或改善轻度认知障碍（MCI）患者认知功能的潜在机制-MCI是正常衰老和AD之间的过渡阶段。这项研究的结果对于开发有效的干预措施来预防或减缓阿尔茨海默病具有潜在的重要意义。