Exercise to improve hippocampal connectivity and learning in older adults

锻炼可改善老年人的海马连接和学习能力

• 批准号: 9902292
• 负责人: MICHELLE WEBB VOSS
• 金额: $ 70.7万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9902292
• 关键词: Acute; Adult; Adverse effects; Affect; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Animal Model; Animals; Area; Automobile Driving; Blood Vessels; Brain; Brain region; Cardiac; Cognition; Cognitive; Cognitive aging; Communication; Complex; Cost of Illness; Data; Detection; Deterioration; Elderly; Exercise; Exercise Test; Functional Magnetic Resonance Imaging; Goals; Growth; Health; Hippocampus (Brain); Hour; Human; Impaired cognition; Individual Differences; Intervention; Lead; Learning; Life; Long-Term Effects; Measures; Memory; Metabolic; Modality; Motor; Neurosciences; Onset of illness; Pathway interactions; Physical Exercise; Physiological; Physiological Processes; Population; Prefrontal Cortex; Prevention; Prevention strategy; Process; Randomized Controlled Trials; Research; Risk; Sampling; Testing; Therapeutic; Time; Training; Translating; Work; age effect; base; cardiorespiratory fitness; cognitive benefits; cognitive function; cost; endurance exercise; exercise intensity; exercise training; healthy aging; improved; innovation; insight; light intensity; memory process; novel; predicting response; relating to nervous system; relational memory; response; success; trial comparing

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.

项目摘要 鉴于老年人比例增加，并且随着衰老的逐渐认知能力下降，有一个 迫切需要治疗与年龄有关的认知能力下降的需求。动物模型坚固 支持耐力运动可以保护容易衰老的大脑区域，例如海马和 这些好处会带来更好的学习。相比之下，人类研究的发现混合了 健康老年人运动的认知益处。这种对比表明我们仍然没有 了解运动如何改变成年人衰老的认知能力下降。但是，不 人类研究对学习老年人的认知对运动影响进行了全面测试 基本运动神经科学启发的任务。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具有相同类型的学习的老年人，转化差距 显示通过改善海马功能来改善动物模型。这将使我们更接近 我们确定运动如何保护大脑免受衰老的不利影响的长期目标 开发干预措施，以最大程度地减少与年龄相关的认知能力下降。我们的总体假设是 锻炼会在增加功能性海马体沟通时改善学习 否则随着衰老而下降。我们将通过确定是否是否 中等强度运动的功能性海马皮质连通性提高 学习一系列需要海马来获得新的关系记忆的任务 不在不需要海马学习的任务中学习，例如运动或响应学习。我们进一步 通过确定个人差异是否在 中等强度锻炼对海马体皮层连通性的快速影响预测训练相关 连通性和学习的变化，以及确定与训练相关的心肺变化 健身是关键因素。我们的结果将是重要的，因为早期预防的影响最大 并确定运动如何抵消认知衰老的机制导致理解如何 这种可塑性是可能的，并为预防策略提供了信息。拟议的工作是创新的，因为 我们通过将概念上的高级度量汇总在一起来测试运动如何影响认知 海马依赖于学习和记忆过程，具有新颖的概念化 捕获改变海马皮层连通性的运动引起的生理变化。 由于海马连通性随着阿尔茨海默氏症而恶化，因此结果也可能导致 了解运动可以减少这种毁灭性和昂贵疾病的风险的机制。