Modulatory Effects of Fitness on Hippocampal Dependent Memory Across the Lifespan

一生中健身对海马依赖性记忆的调节作用

• 批准号: 9377478
• 负责人: Rachel K Nauer
• 金额: $ 3.24万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2019-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9377478
• 关键词: Address; Adult; Aerobic; Aerobic Exercise; Age; Aging; Alzheimer' s Disease; Animal Model; Attenuated; Behavioral; Brain; Brain region; Cognitive; Data; Elderly; Episodic memory; Exercise; Exercise Physiology; Experimental Designs; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Hippocampus (Brain); Human; Impaired cognition; Individual; Intervention; Knowledge; Learning; Link; Longevity; Memory; Methods; Neurobehavioral Manifestations; Neurodegenerative Disorders; Neurons; Older Population; Outcomes Research; Pathologic; Pathology; Pattern; Performance; Physical Fitness; Prevalence; Preventive Intervention; Process; Research; Research Project Grants; Resolution; Role; Signal Transduction; Specific qualifier value; Stimulus; System; Task Performances; Time; Training; Variant; adult neurogenesis; age effect; age group; age related; aging brain; aging population; cardiorespiratory fitness; cognitive neuroscience; cost; dentate gyrus; entorhinal cortex; exercise intervention; experimental study; fitness; hippocampal subregions; improved; inter-individual variation; middle age; negative affect; neurobiological mechanism; neuroimaging; neuromechanism; newborn neuron; novel; pre-clinical; predictive marker; rapid growth; skills; young adult

PROJECT SUMMARY/ABSTRACT Aerobic exercise is thought to promote healthy brain aging and to attenuate cognitive decline in seniors, and may protect from neurodegenerative disorders like Alzheimer's dementia (AD). AD is characterized by a profound pathology of the hippocampus (HC) and entorhinal cortex, two brain regions that are critical for episodic memory formation. In animal models, aerobic exercise has been shown to increase the number of adult-born hippocampal neurons. In turn, newborn neurons have been shown to improve learning and memory. Studies in humans have shown that better aerobic fitness is associated with greater performance on memory tasks in both young and older adults, but this has yet to be studied in middle-aged adults. Given the increasing prevalence of AD, research has focused on preclinical stages, prior to emergence of cognitive symptoms. In this context, examining the middle-age range is crucial, because it may be the beginning of subtle cognitive or brain changes predictive of future AD. Additionally, neuroprotective interventions may be most successful the earlier they are implemented. The goal of the proposed project is to determine the neurobiological mechanisms of hippocampal-related plasticity from a cognitive neuroscience perspective by focusing on the hippocampal subfields, which are known to be negatively affected by aging, and elucidate how fitness may modulate these mechanisms across adulthood. Aim 1 of this proposal focuses on determining the effects of aging on the behavioral capacity to disambiguate overlapping stimuli during memory formation cross-sectionally throughout adulthood. The goal of Aim 2 is to elucidate how the relationship between task performance and age may be modulated by objectively assessed aerobic fitness. Aim 3 focuses on hippocampal subfield function associated with memory formation. Aim 3 will utilize high-resolution fMRI and data-driven analytic approaches uniquely suited for detecting subtle functional changes within hippocampal subfields. Training goals include gaining expertise in 1) state-of-the-art exercise physiology methods, and developing skills in 2) experimental design for behavioral and fMRI experiments, and 3) novel data-driven approaches to analysis. The central research hypotheses are that age will be positively associated with increased performance variability during the middle age range (Aim #1), that this performance variability will interact with fitness (Aim #2), and that aerobic fitness will also modulate hippocampal activation patterns underlying memory formation (Aim #3). This research project will enhance the knowledge of the effects of early aging on hippocampal plasticity and will set a foundation from which to identify individuals who may benefit from early neuroprotective interventions.

项目总结/摘要 有氧运动被认为可以促进健康的大脑老化，减轻老年人的认知能力下降， 可以防止神经退行性疾病，如阿尔茨海默氏痴呆症（AD）。AD的特征在于 海马体（HC）和内嗅皮层的深刻病理学，这两个大脑区域对于 情景记忆的形成在动物模型中，有氧运动已被证明可以增加 成年海马神经元反过来，新生神经元已被证明可以改善学习和记忆。 对人类的研究表明，更好的有氧健身与更好的记忆力有关 在年轻人和老年人的任务，但这还有待研究在中年人。鉴于越来越 在AD的流行中，研究集中在认知症状出现之前的临床前阶段。在 在这种情况下，检查中年范围是至关重要的，因为它可能是微妙的认知或 大脑变化预测未来AD。此外，神经保护干预可能是最成功的， 他们早些时候就实施了。 该项目的目标是确定与脑缺血相关的神经生物学机制。 可塑性从认知神经科学的角度，通过集中在海马子领域，这是 已知是由老化的负面影响，并阐明如何健身可以调节这些机制， 成年该提案的目标1侧重于确定衰老对行为能力的影响， 在整个成年期的记忆形成过程中消除重叠的刺激。的目标 目的2是阐明任务绩效与年龄的关系如何受到客观因素的调节 评估有氧健身。目的3：研究海马亚区与记忆形成的关系。 Aim 3将利用高分辨率fMRI和数据驱动的分析方法， 海马亚区的功能变化。培训目标包括获得1）最先进技术的专业知识 运动生理学方法，并在2）行为和功能磁共振成像实验设计中发展技能 实验，和3）新的数据驱动的分析方法。主要的研究假设是， 将与中年期间性能变异性增加呈正相关（目标1）， 这种性能变化将与健身（目标#2）相互作用，有氧健身也将调节 海马激活模式是记忆形成的基础（目标#3）。该研究项目将提高 了解早期衰老对海马可塑性的影响，并将为 识别可能受益于早期神经保护干预的个体。