Antioxidant Imaging Marker of Investigating Gains in Neurocognition in an Intervention Trial of Exercise (AIM-IGNITE)

研究运动干预试验中神经认知增益的抗氧化成像标记 (AIM-IGNITE)

基本信息

批准号：
10321247
负责人：
Phil Lee
金额：
$ 53.65万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-15 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10321247
关键词：
Accounting Address Adult Aerobic Exercise Age Age-associated memory impairment Aging Agreement Alzheimer&apos s Disease Alzheimer&apos s disease risk American Ancillary Study Antioxidants Behavior Therapy Biological Biological Process Brain Cells Cerebrovascular Circulation Cerebrum Clinical Cognitive Communities Consumption Data Disease Dose Elderly Exercise Genetic Genetic Markers Glutathione Goals Healthcare Human Image Impaired cognition Incidence Individual Intervention Trial Laboratories Life Style Link Magnetic Resonance Magnetic Resonance Imaging Measures Mediating Methods Mission Molecular Molecular Genetics Monitor Nerve Degeneration Neurocognition Outcome Oxidative Stress Participant Patients Phase III Clinical Trials Physical activity Physiological Predisposition Prevalence Public Health Quality of life Randomized Recommendation Secondary Progressive Multiple Sclerosis System Techniques United States National Institutes of Health Work abeta deposition aging brain aging population apolipoprotein E-4 base brain health brain tissue brain volume cognitive function cognitive performance cohort cost effective dementia risk design exercise intensity exercise intervention fight against imaging biomarker imaging genetics improved in vivo indexing innovation molecular marker neuroimaging neuroimaging marker neuroprotection new therapeutic target novel older patient oxidative damage physical inactivity prevent response therapy design

项目摘要

PROJECT SUMMARY / ABSTRACT The absence of effective methods for treating age-relate cognitive decline presents a significant public health problem, considering its ubiquity with unprecedented increases in the aging population. Recently, lifestyle choices, particularly exercise, have been noted as potential effective strategies for maintaining and enhancing brain health and cognitive function in older adults. However, the public and scientific community is yet to reach agreements on the conclusive benefits of exercise on the brain. Currently a Phase III clinical trial: IGNITE (Investigating Gains in Neurocognition in an Intervention Trial of Exercise) is ongoing to address the ambiguity in influences of exercise on brain health and cognitive function in older adults. We propose an ancillary study to determine the impact of exercise on antioxidant status in the brain of participants drawn from IGNITE, in which clinical, imaging, genetic, molecular and physiological measures will be acquired. We will determine the association of antioxidant status with cognitive function and brain health as well as the impact of genetic and molecular risk factors of Alzheimer's disease (AD) on these relationships. Our long-term goal is 1) to identify the underlying mechanisms of improved brain health and cognitive performance associated with behavioral interventions and/or new targeted therapies in older adults, and 2) to offer novel possibilities for directly monitoring the impact of these emergent treatment options through new quantitative, non-invasive neuroimaging indices of brain health in aging, AD and AD-related diseases. Our overall hypothesis is that exercise enhances cerebral antioxidant defenses to fight against oxidative stress in the aging brain by increasing the levels of glutathione (GSH), which leads to improved brain health and cognitive function. GSH is a key component of the cerebral antioxidant system, which is consumed to protect cells against oxidative damage resulting in lower GSH levels in brain tissue. Our preliminary data suggest that brain GSH is related with the cognitive performance of older adults in multiple domains, lowered in aging and AD, and increases after exercise interventions. The Specific Aims are: (1) to determine the influence of exercise intervention on the brain antioxidant status in the aging brain, (2) to determine the mediating relationship between the brain antioxidant status and exercise-associated improvements in cognitive function and brain health, and (3) to examine modulating effects of genetic/molecular markers of Alzheimer's disease on changes in brain antioxidant status after exercise intervention. The expected outcome of this project is 1) the identification of a major mechanism, oxidative stress, underlying the beneficial effects of exercise on cognitive function and brain health seen in older adults, 2) the identification of a mechanism-based neuroimaging marker reflecting neuromodulating effects of exercise intervention and the dose-response effects, and 3) the identification of exercise intervention as an important strategy to enhance neuroprotection via increased cerebral antioxidant defenses.

项目概要/摘要缺乏治疗与年龄相关的认知能力下降的有效方法，引起了公众的广泛关注。考虑到健康问题随老龄人口空前增加而普遍存在。最近，生活方式的选择，特别是锻炼，已被认为是维持和维持健康的潜在有效策略。增强老年人的大脑健康和认知功能。然而，公众和科学界尚未就运动对大脑的最终益处达成一致。目前处于Ⅲ期临床试验：IGNITE（调查运动干预试验中神经认知的增益）正在进行中，以解决运动对老年人大脑健康和认知功能的影响的模糊性。我们提出一个确定运动对参与者大脑抗氧化状态影响的辅助研究来自 IGNITE，其中将获得临床、影像、遗传、分子和生理测量。我们将确定抗氧化状态与认知功能和大脑健康以及阿尔茨海默病 (AD) 的遗传和分子风险因素对这些关系的影响。我们的长期目标是 1) 确定改善大脑健康和认知的潜在机制与老年人的行为干预和/或新的靶向治疗相关的表现，以及 2) 通过新的方法直接监测这些紧急治疗方案的影响提供了新的可能性衰老、AD 和 AD 相关疾病中大脑健康的定量、非侵入性神经影像指标。我们的总体假设是，运动可以增强大脑抗氧化防御能力，以对抗氧化应激通过增加谷胱甘肽 (GSH) 水平来延缓大脑衰老，从而改善大脑健康认知功能。 GSH 是大脑抗氧化系统的关键组成部分，消耗它可以保护大脑细胞抵抗氧化损伤，导致脑组织中谷胱甘肽水平降低。我们的初步数据表明，大脑 GSH 与老年人的认知表现有关多个领域，在衰老和 AD 中降低，在运动干预后增加。具体目标是：（1）确定运动干预对衰老大脑中大脑抗氧化状态的影响， (2)确定大脑抗氧化状态与运动相关之间的中介关系认知功能和大脑健康的改善，以及（3）检查调节作用阿尔茨海默病的遗传/分子标记对运动后大脑抗氧化状态变化的影响干涉。该项目的预期成果是 1）确定了一个主要机制，即氧化压力是运动对老年人认知功能和大脑健康产生有益影响的基础， 2）基于机制的神经影像标记的鉴定，反映神经调节作用运动干预和剂量反应效应，以及3）将运动干预确定为一种通过增加脑抗氧化防御来增强神经保护的重要策略。