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: 8325547
• 负责人: Richard P SLOAN
• 金额: $ 59.97万
• 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/8325547
• 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; young adult

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.

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.