The entorhinal cortex and aerobic exercise in aging

衰老过程中的内嗅皮层和有氧运动

• 批准号: 9111578
• 负责人: Karin Schon
• 金额: $ 27.32万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9111578
• 关键词: Adult; Aerobic; Aerobic Exercise; Affect; Age; Aging; Aging-Related Process; Alzheimer' s Disease; Anatomy; Animal Experimentation; Animal Model; Area; Atrophic; Attention; Attenuated; Behavior assessment; Brain; Clinical Trials; Cognition; Cognitive; Cognitive aging; Communication; Control Groups; Cross-Sectional Studies; Elderly; Employee Strikes; Environment; Exercise; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Hippocampus (Brain); Human; Impaired cognition; Individual; Knowledge; Laboratories; Life Style; Magnetic Resonance Imaging; Measures; Medial; Mediating; Memory; Methods; Mission; National Institute on Aging; Neurobiology; Participant; Pathology; Patients; Performance; Physical Exercise; Quality of life; Randomized; Randomized Controlled Clinical Trials; Research; Resolution; Risk; Rodent; Signal Transduction; System; Task Performances; Techniques; Temporal Lobe; Testing; Thick; Vertebral column; Visual; Visuospatial; active control; aging brain; base; behavior test; brain size; cognitive task; cognitive testing; dentate gyrus; effective intervention; entorhinal cortex; environmental enrichment for laboratory animals; executive function; exercise training; fitness; flexibility; follow-up; functional disability; hippocampal atrophy; improved; loss of function; mild cognitive impairment; neuroimaging; neurophysiology; post intervention; public health relevance; response; skills; spatial memory; virtual reality; volunteer; way finding

 DESCRIPTION (provided by applicant): The overall goal of this project is to investigate the response of the entorhinal-hippocampal memory system to aerobic exercise training in initially physically inactive, healthy seniors. Entorhinal-hippocampal communication is critical for successful navigation and context-dependent memory formation. This region shows profound pathology in Alzheimer's disease. Entorhinal and hippocampal atrophy rates accelerate with age in cognitively intact seniors, who also show impaired navigation and reduced activity in hippocampal and parahippocampal areas during allocentric navigation. Allocentric navigation is a form of flexible navigation that depends on successful encoding of relationships between landmarks in the environment. Physical exercise consistently appears as one of the most effective interventions to attenuate cognitive decline in Alzheimer's disease, and promotes healthy cognitive and brain aging, including the hippocampus. The entorhinal cortex has direct projections to the dentate gyrus, the neurogenic zone of the hippocampus, which is known to respond strongly to exercise in animal models. Environmental enrichment promotes not only hippocampal integrity, but also in- creases cortical thickness in the entorhinal cortex in rodents. Animal research has demonstrated that physical exercise is one of the critical variables for environmental enrichment induced brain changes. In humans, it is currently unknown what mechanisms underlie these changes, and if aerobic exercise has an impact on entorhinal integrity and entorhinal-hippocampal communication. It is fundamentally important to fill this knowledge gap, because the entorhinal cortex sits at the epicenter of inputs to the hippocampus, serving as a gateway for cortical-hippocampal communications. We hypothesize that the entorhinal cortex and entorhinal-hippocampal communication are primary functional/anatomic targets of aerobic exercise. In two Specific Aims we seek to test the hypothesis that entorhinal functional integrity and entorhinal-hippocampal functional connectivity during memory task performance (Specific Aim #1) and during allocentric navigation in a virtual environment (Specific Aim #2) are enhanced following exercise training in initially physically inactive seniors and that this enhancement is positively related to changes in cognition. We will also investigate whether particular subsets of participants, such as those with poor performance on spatial reasoning tests or those with greater entorhinal atrophy, might be more responsive to aerobic exercise. To investigate these aims, we will use a randomized, controlled clinical trial of exercise training with baseline and follow-up assessments of behavioral performance on cognitive tasks of entorhinal and hippocampal integrity, aerobic fitness, and brain function using high-resolution functional and structural MRI techniques optimized for examining the entorhinal-hippocampal memory system. The proposed project is directly relevant to the mission of the National Institute on Aging through its focus on understanding the neurobiological underpinnings of the aging process with the goal to promote healthy cognitive and brain aging through lifestyle changes.

 描述（由适用提供）：该项目的总体目标是调查最初身体不活跃，健康的老年人对有氧运动训练的内嗅 - 海马记忆系统的反应。内河海马沟通对于成功导航和上下文依赖性内存形成至关重要。该地区在阿尔茨海默氏病中显示出深刻的病理。在认知完整的老年人中，内hinal和海马萎缩率随着年龄的增长而加速，他们在中心航行期间还表现出海马和帕拉希帕帕省地区的活动受损和减少的活动。同类导航是一种灵活导航的一种形式，取决于在环境中的地标之间的关系成功编码。体育锻炼始终是减弱阿尔茨海默氏病认知能力下降的最有效干预措施之一，并促进包括海马在内的健康认知和脑老化。内嗅皮层的直接项目是向海马的神经源性带齿状回，众所周知，在动物模型中对运动的反应强烈。环境富集不仅促进了海马完整性，而且还促进了啮齿动物内嗅皮层的皮质厚度。 动物研究表明，体育锻炼是环境富集引起的大脑变化的关键变量之一。在人类中，目前尚不清楚这些变化是哪些机制以及有氧运动对内hinal的完整性和肠胃 - 海马交流的影响。填补这一知识差距至关重要，因为内嗅皮层位于海马的投入中心，是皮质 - 海马通信的门户。我们假设内嗅皮层和内嗅 - 海马通信是有氧运动的主要功能/解剖靶标。在两个具体的目标中，我们试图检验以下假设：在记忆任务性能（特定目标＃1）和在虚拟环境中的同类导航期间（特定的AIM＃2）在最初不活跃的老年人和这种增强与Cognition的更改相关的最初相关的锻炼之后，增强了在虚拟环境中（特定的AIM＃2）在虚拟环境中增强运动训练后，在记忆任务执行过程中（特定的目标＃2）在中心导航期间得到了增强。我们还将调查特定的参与者子集，例如在空间推理测试中表现较差的参与者或赤道萎缩较高的参与者是否可能对有氧运动更敏感。为了调查这些目标，我们将使用一项随机对照的临床试验 使用基线和海马完整性，有氧健身和大脑功能的锻炼训练和随访评估，并使用高分辨率功能和结构MRI技术优化了用于检查肠hin鼻 - 洪门场记忆系统的高分辨率功能和结构MRI技术。拟议的项目与美国国立衰老研究所的使命直接相关，因为它专注于了解衰老过程的神经生物学基础，目的是通过改变生活方式的改变来促进健康的认知和大脑衰老。