Mild Cognitive Impairment: Cerebrovascular Dysfunction and Exercise Training

描述（由申请人提供）：随着年龄的增长，保持认知活力，降低阿尔茨海默病（AD）的风险是迫切的国家卫生优先事项。本次修订的目的是加强目前资助的“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可以减轻轻度认知障碍（MCI）患者的脑淀粉样蛋白负担并改善慢性脑炎症-轻度认知障碍（MCI）是正常衰老和AD之间的过渡阶段。具体实现以下目标。目的1：确定运动训练是否能减轻轻度认知损伤患者的脑淀粉样蛋白负担。在有氧运动训练前后，MCI患者的脑淀粉样蛋白负担将通过正电子发射断层扫描（PET）淀粉样蛋白成像（18F-AV-45）和脑脊液（CSF） A2、tau和磷酸化tau水平的免疫测定（ELISA）进行测量。目的2：确定运动训练是否能改善轻度认知损伤患者的慢性脑炎。MCI患者的慢性脑炎将使用定量多重免疫分析法来评估血浆和脑脊液中炎症生物标志物（如TNF-1、IL-12和IL-6）的水平。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。脑灌注将使用无创经颅多普勒和灌注MRI（通过动脉自旋标记技术）进行测量。与父母资助一起，我们还将确定这些神经影像学和炎症生物标志物的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，在衰老过程中保持认知活力，预防或减缓阿尔茨海默病至关重要。

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.