Exercise, Age-Related Memory Decline, and Hippocampal Function.

运动、与年龄相关的记忆衰退和海马功能。

• 批准号: 7986086
• 负责人: Richard P SLOAN
• 金额: $ 57.69万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7986086
• 关键词: Address; Adult; Aerobic; Aerobic Exercise; Affect; Age; Age-associated memory impairment; Aging; Aging-Related Process; Animals; Area; Attenuated; Behavior Therapy; Blood Volume; Brain; Brain region; Censuses; Cerebrovascular Circulation; Cerebrum; Cognitive; Cognitive aging; Control Groups; Data; Development; Diffuse; Elderly; Enrollment; Epidemic; Evaluation; Exercise; Family; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Healthcare Systems; Hippocampal Formation; Hippocampus (Brain); Housing; Human; Impaired cognition; Individual; Intervention; Learning; Length; Life; Literature; Longevity; Mediating; Mediation; Mediator of activation protein; Memory; Molecular; Morbidity - disease rate; Mus; Neurons; Neuropsychological Tests; Performance; Population; Process; Public Policy; Randomized; Regimen; Research; Resolution; Sampling; Slide; Societies; Spin Labels; Staging; Testing; Time; Training; United States; Variant; Waiting Lists; age related; aging population; cognitive function; dentate gyrus; frontal lobe; healthy aging; hippocampal subregions; improved; improved functioning; in vivo; intervention effect; mortality; normal aging; programs; public health relevance

DESCRIPTION (provided by applicant): In the US, increased length of life and reduced morbidity and mortality have resulted in a growing number of older adults, the demographic "time bomb" often referred to in discussions of public policy. According to the Census Bureau, the population aged 65 and over will double in size within the next 25 years. Moreover, these older adults will live healthier lives than their predecessors. While this increased length of a healthy life is an undeniable societal benefit, it brings with it a major societal problem: an epidemic of aging-related cognitive decline. The need to develop interventions to address this growing problem is urgent. Aging-related cognitive dysfunction is not diffuse; rather it targets selected brain areas, in particular the frontal lobes and the hippocampal formation. The separate but interconnected subregions of the hippocampus are differentially vulnerable to pathogenic mechanisms, including the normal aging process. A range of in vivo and post-mortem studies have converged on the dentate gyrus (DG) as the hippocampal subregion differentially targeted by the aging process. As with pathogenic processes, any intervention that improves brain function does so with regional selectivity. One such intervention is physical exercise, which has been shown to improve both frontal lobe and hippocampal function. Using a high-resolution variant of functional magnetic resonance imaging (fMRI), we have demonstrated that aerobic training selectively benefitted DG function both humans and mice. In addition, improvement in DG function was associated with improved performance on a word list learning task but not in tasks conventionally thought to be frontal lobe dependent. The human part of the study had significant shortcomings, however: it was small (N = 11), lacked a control group, enrolled only young subjects (age 20-45 years), and employed only a limited neuropsychological testing battery. The overall goal of this proposal is to use the high-resolution variant of fMRI to test the hypothesis that aerobic training will induce improvements in DG function in a sample of younger (age 20-35) and older (50-65) adults, assigned randomly to an active training condition or wait list control group. We will use more comprehensive neuropsychological testing to examine the relationship between changes in DG function and selected cognitive capacities. Taken together with the observation that normal aging differentially targets the DG, this research program will establish that physical exercise is an effective approach for ameliorating the insidious cognitive slide that occurs in all of us as we age. Thus, the potential significance of this application is substantial. PUBLIC HEALTH RELEVANCE: According to the US Census Bureau, the United States population aged 65 and over is expected to double in size within the next 25 years, and this "demographic time bomb" will bring with it an epidemic of aging-related cognitive decline, imposing burdens on individuals and their families and on the healthcare system and society as a whole. The need to understand the pathophysiology of cognitive decline and then develop interventions to address this growing problem is urgent and in this application, we propose to test the impact of aerobic exercise training on cognitive function in a sample of young and older adults. In addition, because recent evidence suggests that 1) the dentate gyrus (DG) of the hippocampal formation is differentially targeted by cognitive aging and 2) that exercise improves DG function, we also use fMRI to test whether exercise-induced improvement in cognitive function is mediated by increased cerebral blood volume to the DG.

描述（由申请人提供）：在美国，寿命的增加，发病率和死亡率降低导致越来越多的老年人，在公共政策讨论中经常提到的人口“定时炸弹”。根据人口普查局的说法，在未来25年内，年龄在65岁及以上的人口将翻一番。此外，这些老年人将比前任更健康。 尽管健康生活的长度增加是不可否认的社会利益，但它带来了一个主要的社会问题：与衰老有关的认知能力下降的流行。迫切需要制定干预措施来解决这一日益严重的问题。 与衰老相关的认知功能障碍不是分散的。相反，它针对选定的大脑区域，尤其是额叶和海马形成。海马的独立但相互联系的子区域在差异上容易受到致病机制的影响，包括正常的衰老过程。一系列的体内和验尸研究已在齿状回（DG）上汇总，因为海马子区域由衰老过程差异化。 与致病过程一样，任何改善大脑功能的干预措施都可以通过区域选择性。一种这样的干预是体育锻炼，已证明可以改善额叶和海马功能。使用功能性磁共振成像（fMRI）的高分辨率变体，我们证明有氧训练有选择地使DG功能受益于人类和小鼠。此外，DG功能的改善与单词列表学习任务上的性能提高有关，但在常规上被认为是额叶依赖性的任务中没有相关的。但是，该研究的人类部分存在很大的缺点：它很小（n = 11），缺乏对照组，仅招募了年轻受试者（20-45岁），并且仅采用有限的神经心理测试电池。 该提案的总体目标是使用fMRI的高分辨率变体来检验以下假设：有氧训练将在年轻（20-35岁）及以上（50-65岁）成年人的样本中诱导DG功能的改善，并随机分配为主动训练条件或等待列表对照组。我们将使用更全面的神经心理学测试来检查DG功能变化与选定的认知能力之间的关系。 通过观察到正常老化针对DG的观察结果，该研究计划将确定体育锻炼是改善我们所有人随着年龄的所有人而发生的阴险认知幻灯片的有效方法。因此，该应用的潜在意义是很大的。 公共卫生相关性：根据美国人口普查局的说法，美国65岁及65岁以上的美国人口预计在未来25年内将增加一倍，而这种“人口统计计时炸弹”将带来与衰老相关的认知能力下降的流行，对个人及其家人以及医疗保健系统和整个社会施加痛苦。紧迫地了解认知能力下降的病理生理，然后制定干预措施以解决这一增长问题，在这种应用中，我们建议在年轻和老年人样本中测试有氧运动训练对认知功能的影响。此外，由于最近的证据表明1）海马形成的齿状回（DG）是通过认知衰老差异地靶向的，而2）锻炼可以改善DG功能，我们还使用fMRI来测试运动诱导的认知功能的改善是否介导了认知功能的改善，这是由增加的脑血容量介导的DG。