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)

• 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
• 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' s Disease; Alzheimer' 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

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.

项目摘要 /摘要 没有有效治疗年龄相关认知能力下降的有效方法呈现出重要的公众 健康问题，考虑到其普遍存在，人口老龄化的空前增加。最近， 生活方式的选择，尤其是运动，已被认为是维护和 增强大脑健康和老年人的认知功能。但是，公共和科学界是 尚未达成关于运动在大脑上的决定性好处的协议。目前是III期临床 试验：IGNITE（在锻炼干预试验中调查神经认知的收益）正在进行解决 运动影响对老年人大脑健康和认知功能的影响。我们提出了一个 辅助研究确定运动对参与者大脑中抗氧化状态的影响 从IGNITE中，将获取临床，成像，遗传，分子和生理措施。我们 将确定抗氧化剂状态与认知功能和大脑健康的关联以及 阿尔茨海默氏病（AD）对这些关系的遗传和分子危险因素的影响。 我们的长期目标是1）确定改善大脑健康和认知能力的潜在机制 与老年人的行为干预措施和/或新的靶向疗法相关的表现，2） 提供新的可能性，以直接监视这些新兴治疗方案的影响 衰老，AD和AD相关疾病中脑健康的定量，非侵入性神经影像学指标。我们的 总体假设是，运动增强了脑抗氧化剂防御措施，以抵抗氧化应激 通过增加谷胱甘肽（GSH）的水平，大脑衰老，从而改善了大脑健康和 认知功能。 GSH是脑抗氧化剂系统的关键组成部分，该系统被消耗供保护 针对氧化损伤的细胞导致脑组织中GSH水平较低。 我们的初步数据表明，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，运动干预后增加。具体目标 是：（1）确定运动干预对衰老大脑脑抗氧化剂状态的影响， （2）确定大脑抗氧化剂状态与运动相关的中介关系 认知功能和大脑健康的改善，以及（3）检查调节作用 阿尔茨海默氏病的遗传/分子标记在运动后脑抗氧化状态的变化 干涉。该项目的预期结果是1）鉴定主要机制，氧化 压力，锻炼对老年人的认知功能和大脑健康的有益影响的基础， 2）鉴定基于机制的神经影像学标记，反映了神经调节作用 运动干预和剂量反应效应，以及3）将运动干预识别为 通过增加的脑抗氧化剂防御力来增强神经保护作用的重要策略。