Examining the Persistence of Neurocognitive Benefits of Exercise

项目总结/摘要 身体活动（PA）是缓解与年龄相关的认知能力下降的最有前途的方法之一， 痴呆症的风险，但很少有针对大脑健康结果的足够有力的随机临床试验（RCT） 已经进行了。此外，我们对大脑的生物学通路和调节机制知之甚少 对锻炼的反应。为了解决这些差距，我们进行了一次多地点，监督，剂量反应 （150 min/wk中等强度; 225 min/wk中等强度; 150 min/wk光照强度），有氧 在648名认知正常的成年人中进行了一项以大脑健康结果为主要终点的运动RCT， 65-80岁。这项研究，在运动干预试验中调查神经认知的增益 （IGNITE）于2016年由NIH资助。RCT在超过 样本量预期，保持较高的依从性和合规性（>80%），最小的缺失数据， 改善心肺功能，实现代表性不足的少数民族的预期分布 (25%非白人）。IGNITE的结果必将是变革性的，但仍将有许多 在IGNITE结束后，我们打算在本提案中解决尚未回答的问题。比如说， 一项为期12个月的有氧运动RCT是否对认知、神经或 完成干预后5年的神经病理学结局？RCT是否有效， 改变长期锻炼行为我们能否利用IGNITE丰富的参与者数据来预测谁是 在完成干预后更有可能保持积极的生活方式？效果如何 运动RCT在5年内改变阿尔茨海默病（AD）神经病理学的积累 后续？最后，如果认知、大脑或神经病理学的标志物作为一种功能在群体中不同， 在完成干预后5年的分配中，哪些因素介导了这些长期效益？ 这些问题的答案将具有重大的科学和公共卫生意义，我们将 通过对IGNITE参与者进行5年后续评估，以具有成本效益的方式解决这一问题。我们 专注于4个关键目标和一个发现科学目标：目标1：测试IGNITE练习RCT对 干预完成后5年的认知表现。目标2：审查在多大程度上 参与者在干预完成后5年保持锻炼行为。目标3：测试 干预是否改变了AD神经病理学的5年累积。目标4：测试 运动随机对照试验影响脑健康神经影像学指标的5年随访。探索科学目标： 探索基线参与者特征是否可预测长期参与运动行为 在干预结束后。

Project Summary/Abstract Physical activity (PA) is one of the most promising approaches for mitigating age-related cognitive decline and risk for dementia, yet few sufficiently powered randomized clinical trials (RCT) targeting brain health outcomes have been conducted. Further, little is known about the biological pathways and moderators of the brain response to exercise. To address these gaps, we have conducted a multi-site, supervised, dose-response (150min/wk of moderate-intensity; 225min/wk of moderate-intensity; 150min/wk of light intensity), aerobic exercise RCT with brain health outcomes as the primary endpoints in 648 cognitively normal adults between 65-80 years of age. This study, Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE), was funded by the NIH in 2016. The RCT has been enormously successful in terms of exceeding sample size expectations, maintaining high adherence and compliance (>80%), minimal missing data, improving cardiorespiratory fitness, and achieving the expected distribution of under-represented minorities (25% non-white). The results from IGNITE are bound to be transformative, but there will remain many unanswered questions after the conclusion of IGNITE that we intend to address in this proposal. For example, does a 12-month aerobic exercise RCT have any persistent or protracted benefits to cognitive, neural, or neuropathological outcomes 5-years after the completion of the intervention? Was the RCT effective at modifying long-term exercise behaviors? Can we utilize the rich participant data of IGNITE to forecast who is more likely to maintain a physically active lifestyle after the completion of the intervention? How effective was the exercise RCT for modifying the accumulation of Alzheimer’s disease (AD) neuropathology over a 5-year follow-up? And, finally, if cognitive, brain, or markers of neuropathology are different as a function of group assignment 5-years after the completion of the intervention, which factors mediate those long-term benefits? The answers to these questions will have significant scientific and public health implications that we will address in a cost-effective manner by conducting a 5-year follow-up evaluation of IGNITE participants. We focus on 4 key aims and one discovery science aim: Aim 1: Test the effects of the IGNITE exercise RCT on cognitive performance 5-years after the completion of the intervention. Aim 2: Examine the extent to which participants maintained exercise behaviors 5-years after the completion of the intervention. Aim 3: Test whether the intervention modified 5-year accumulation of AD neuropathology. Aim 4: Test whether the exercise RCT influenced 5-year follow-up of neuroimaging markers of brain health. Discovery Science Aim: Explore whether participant characteristics at baseline predict long-term engagement in exercise behaviors after the completion of the intervention.