Exercise to improve hippocampal connectivity and learning in older adults

项目摘要 鉴于老年人的比例不断上升，认知能力随着年龄的增长而逐渐下降，存在着 迫切需要治疗方法来补救与年龄相关的认知衰退。健壮的动物模型 支持耐力运动保护大脑易受衰老影响的区域，如海马体和 这些好处会带来更好的学习。相比之下，从人体研究中得出的结论却很复杂。 运动对健康老年人的认知益处。这一对比表明，我们仍然没有 了解锻炼如何改变老年人认知能力下降的过程。然而，没有 人体研究全面测试了运动对有学习能力的老年人的认知影响 任务灵感来自基础运动神经科学。我们在拟议的研究中的目标是填补这一点 通过确定运动是否改善了老年人的相同类型的学习来确定翻译差距 在动物模型中已被证明可以通过改善海马体功能来改善。这将使我们更接近 我们的长期目标是确定锻炼如何保护大脑免受衰老的不利影响 制定干预措施，最大限度地减少与年龄相关的认知能力下降。我们的总体假设是 运动可以改善学习，因为它增加了功能性海马区-大脑皮层的交流， 否则就会随着年龄的增长而下降。我们将在健康的老年人样本中测试这一点，方法是确定 中等强度运动增加功能性海马区-皮质连接改善 学习一系列需要海马体才能获得新的关系记忆的任务，但 而不是在不需要海马体学习的任务中，比如运动或反应学习。我们进一步 通过确定个体在运动中的差异来追求对运动的直接影响的机械论洞察 中等强度运动对海马区-皮质连接性的快速影响预测训练相关 连通性和学习的变化，并通过确定训练相关的心肺功能变化 健康是一个关键因素。我们的结果将是重要的，因为早期预防具有最大的影响 并确定运动如何抵消认知老化的机制，从而理解 这种可塑性是可能的，并为预防策略提供了信息。拟议的工作具有创新性，因为 我们通过收集概念上先进的测量方法来测试运动对认知的影响 海马体依赖的学习和记忆过程及其新的概念化 捕捉运动引起的改变海马区-皮质连接性的生理变化。 由于阿尔茨海默氏症患者的海马区连接性恶化，其结果也可能导致 了解锻炼降低这种毁灭性且代价高昂的疾病的风险的机制。

Project Summary Given the rising proportion of older adults and the progressive cognitive decline with aging, there is a pressing need for therapeutics that remediate age-related cognitive decline. Animal models robustly support that endurance exercise protects brain areas vulnerable to aging such as the hippocampus and that these benefits lead to better learning. In contrast, there are mixed findings from human studies on the cognitive benefits of exercise with healthy older adults. This contrast indicates we still do not understand how exercise could change the course of cognitive decline in aging adults. However, no human studies have comprehensively tested exercise effects on cognition in older adults with learning tasks inspired from basic exercise neuroscience. Our objective in the proposed research is to fill this translational gap by determining if exercise improves the same kinds of learning in older adults that have been shown to improve in animal models by improving hippocampal function. This will bring us closer to our long-term goal of determining how exercise protects the brain from adverse effects of aging in order to develop interventions that minimize age-related cognitive decline. Our overall hypothesis is that exercise improves learning when it increases functional hippocampal-cortical communication that otherwise declines with aging. We will test this in a sample of healthy older adults by determining if increases in functional hippocampal-cortical connectivity from moderate intensity exercise improve learning on an array of tasks that require the hippocampus for acquisition of new relational memories but not in tasks that do not require the hippocampus to learn such as motor or response learning. We further pursue mechanistic insight on the direct effects of exercise by determining if individual differences in the rapid effects of moderate intensity exercise on hippocampal-cortical connectivity predict training-related change in connectivity and learning, and by determining if training-related changes in cardiorespiratory fitness are a critical factor. Our results will be significant because early prevention has the biggest impact and determining how exercise counteracts mechanisms of cognitive aging leads to understanding how such plasticity is possible and informs prevention strategies. The proposed work is innovative because we test how exercise affects cognition by bringing together conceptually advanced measures of hippocampal-dependent learning and memory processes with novel conceptualizations for how to capture the physiological changes induced by exercise that change hippocampal-cortical connectivity. Because hippocampal connectivity deteriorates with Alzheimer's, results could also lead to an understanding of the mechanisms by which exercise reduces risk of this devastating and costly disease.