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（由申请人提供）：该项目的总体目标是调查最初身体不活动的健康老年人的内嗅海马记忆系统对有氧运动训练的反应，内嗅海马沟通对于成功导航和环境依赖性至关重要。在认知能力完好的老年人中，该区域显示出阿尔茨海默氏症的深刻病理学特征，其萎缩率随着年龄的增长而加快，他们还表现出导航受损和活动减少。在异中心导航过程中，海马和海马旁区域的异中心导航是一种灵活的导航形式，它依赖于对环境中地标之间关系的成功编码，体育锻炼一直被认为是减轻阿尔茨海默病认知能力下降的最有效干预措施之一。促进健康的认知和大脑老化，包括海马体 内嗅皮层对齿状回（海马体的神经源区）有强烈的直接投射，众所周知，齿状回会做出反应。在动物模型中进行锻炼，丰富的环境不仅可以促进海马体的完整性，还可以增加啮齿类动物内嗅皮层的皮质厚度。 动物研究表明，体育锻炼是环境丰富引起人类大脑变化的关键变量之一，目前尚不清楚这些变化背后的机制是什么，以及有氧运动是否对内嗅完整性和内嗅-海马通讯有影响。对于填补这一知识空白至关重要，因为内嗅皮层位于海马体输入的中心，是皮层-海马体交流的门户。皮层和内嗅-海马通讯是有氧运动的主要功能/解剖目标，在两个具体目标中，我们试图检验这样的假设：在记忆任务执行期间（具体目标#1）和异向导航期间，内嗅功能完整性和内嗅-海马功能连接。在虚拟环境中（具体目标#2），在最初身体不活动的老年人中进行运动训练后，这种增强与认知变化呈正相关，我们还将调查是否有特定的变化。参与者的子集，例如空间推理测试表现不佳的参与者或内嗅萎缩较严重的参与者，可能对有氧运动更敏感。为了研究这些目标，我们将使用一项随机对照临床试验。 使用高分辨率功能和结构 MRI 技术对内嗅和海马完整性、有氧健身和大脑功能的认知任务进行基线和后续行为表现评估的运动训练，该技术针对检查内嗅-海马记忆系统进行了优化。与国家老龄化研究所的使命直接相关，该研究所专注于了解衰老过程的神经生物学基础，目标是通过生活方式的改变促进认知健康和大脑衰老。