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

基本信息

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
项目类别：
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&apos s Disease Alzheimer&apos 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

项目摘要

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）：维持认知活力，并减少阿尔茨海默氏病（AD）的风险是紧急的国家健康重点。这项修订的目的是加强当前资助的授予“轻度认知障碍：脑血管功能障碍和运动训练”（R01 AG033106），以确定有氧运动训练是否会减轻脑部淀粉质负担，并在轻度认知障碍（MCI）（MCI）的慢性脑炎症（MCI）（MCI）之间 - 正常阶段和正常阶段 - 耐磨阶段 - 耐磨阶段。我们将完成以下特定目标。目标1：确定运动训练是否减轻了MCI患者的大脑淀粉样蛋白负担。在一年的有氧运动训练前后，MCI患者的脑淀粉样蛋白负担将通过使用18F-AV-45的正电子发射断层扫描（PET）淀粉样蛋白成像来测量，脑脊髓液（CSF）A2，TAU和磷酸化的TAU的脑脊髓液（ELISA）（ELISA）。目标2：确定运动训练是否可以缓解MCI患者的慢性大脑炎症。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TNF-1，IL-12和IL-6等炎症生物标志物的血浆和CSF水平。目标3：确定脑淀粉样蛋白负担和/或炎症的减少是否与改善脑灌注有关。将使用非侵入性经颅多普勒和灌注MRI（通过动脉自旋标记技术）来测量脑灌注。我们还将与父母赠款一起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。了解运动改善脑部健康的潜在机制对于制定有效的干预措施以维持衰老的认知活力以及预防或减慢阿尔茨海默氏病的状态至关重要。公共卫生相关性：维持衰老的认知活力，并降低阿尔茨海默氏病（AD）的风险是紧急的国家健康重点。这项研究的目的是了解运动障碍患者（MCI）的认知功能（MCI）的基本机制，这是正常衰老和AD之间的过渡阶段。这项研究的结果对于制定有效的干预措施以预防或减缓阿尔茨海默氏病的可能性很重要。