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 考虑到老年人比例的上升和随着年龄的增长认知能力的逐渐下降， 迫切需要治疗与年龄相关的认知能力下降。动物模型稳健 支持耐力运动可以保护大脑中易受衰老影响的区域，如海马体， 这些好处会带来更好的学习效果。相比之下，人类研究的结果喜忧参半， 锻炼对健康老年人的认知益处。这种对比表明，我们仍然没有 了解运动如何改变老年人认知能力下降的过程。但没有 人类研究已经全面测试了运动对老年人认知能力的影响， 从基本的运动神经科学中获得灵感。我们的研究目标是填补这一空白。 通过确定运动是否能改善老年人相同类型的学习， 在动物模型中通过改善海马功能而得到改善。这将使我们更接近 我们的长期目标是确定运动如何保护大脑免受衰老的不利影响， 开发干预措施，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 当运动增加了功能性的大脑皮层交流时， 否则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， 中等强度运动增加的功能性大脑皮层-皮层连接 学习一系列需要海马体获取新的关系记忆的任务， 而不是在不需要海马体学习的任务中，如运动或反应学习。我们进一步 通过确定是否存在个体差异， 中等强度运动对大脑皮层连接的快速影响预测训练相关 连接和学习的变化，并通过确定训练相关的心肺变化 健身是一个关键因素。我们的成果将是重大的，因为早期预防的影响最大 确定运动如何抵消认知老化的机制， 这种可塑性是可能的，并为预防战略提供信息。这项工作具有创新性，因为 我们通过将概念上先进的测量方法结合在一起， 依赖于大脑的学习和记忆过程，以及如何 捕捉运动引起的改变大脑皮层连接的生理变化。 由于海马体的连通性随着阿尔茨海默氏症而恶化，因此结果也可能导致 了解运动降低这种毁灭性和昂贵疾病风险的机制。