Physical Activity and Dementia: Mechanisms of Action

体力活动和痴呆：作用机制

• 批准号: 10625333
• 负责人: Kirk I Erickson
• 金额: $ 61.22万
• 依托单位: ADVENTHEALTH ORLANDO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625333
• 关键词: Address; Adoption; Adult; Alzheimer' s Disease; Alzheimer' s disease related dementia; Behavior; Brain; Cognitive; Cognitive aging; Dedications; Dementia; Emotional; Exercise; Genetic; Genotype; Impaired cognition; Incentives; Incidence; Individual; Individual Differences; Knowledge; Leadership; Measurement; Measures; Mediating; Mentorship; Methods; Neurocognitive; Ocular orbit; Outcome; Participant; Persons; Physical activity; Physiological; Positioning Attribute; Predictive Factor; Prevention; Public Health; Recommendation; Research Proposals; Role; Scientist; Series; Sleep; United States National Institutes of Health; Work; active lifestyle; brain health; cardiometabolism; cardiorespiratory fitness; cognitive function; data repository; exercise prescription; experience; follow-up; individual variation; innovation; predictive modeling; prevent; racial disparity; randomized, clinical trials; response; secondary analysis; Address; Adoption; Adult; Alzheimer' s Disease; Alzheimer' s disease related dementia; Behavior; Brain; Cognitive; Cognitive aging; Dedications; Dementia; Emotional; Exercise; Genetic; Genotype; Impaired cognition; Incentives; Incidence; Individual; Individual Differences; Knowledge; Leadership; Measurement; Measures; Mediating; Mentorship; Methods; Neurocognitive; Ocular orbit; Outcome; Participant; Persons; Physical activity; Physiological; Positioning Attribute; Predictive Factor; Prevention; Public Health; Recommendation; Research Proposals; Role; Scientist; Series; Sleep; United States National Institutes of Health; Work; active lifestyle; brain health; cardiometabolism; cardiorespiratory fitness; cognitive function; data repository; exercise prescription; experience; follow-up; individual variation; innovation; predictive modeling; prevent; racial disparity; randomized, clinical trials; response; secondary analysis

Abstract Exercise is one of the most promising methods for positively influencing neurocognitive function in late adulthood. Yet, despite this recognition, several major knowledge gaps preclude the ability to broadly prescribe exercise to prevent or treat cognitive impairment. This R35 proposal includes a series of innovative and potentially groundbreaking studies that will contribute to major advancements in the field of exercise and brain health. The studies that we describe in this proposal would be led by several highly promising junior scientists with the support of an experienced and dedicated mentorship team. The conceptual and scientific framework for the hypotheses described in this proposal orbit around three major challenges facing the field of exercise and cognitive aging: (1) We have a poor understanding of the mechanisms by which exercise influences cognitive function in late adulthood, (2) We have a poor understanding of the factors that moderate, or explain individual variation in, the response to exercise, and (3) We do not understand the factors that predict long- term adoption of exercise behavior and how to reduce barriers and enhance incentives for individuals who find it challenging to continue to exercise. Despite the clear benefits of an active lifestyle, most people fail to meet public health recommendations for exercise. The more we know about the factors that predict and enhance long-term adoption of exercise, the more we will know about whether exercise influences incidence of Alzheimer’s Disease and best practices for prescribing and maintaining exercise for the prevention and treatment of cognitive impairment. We propose to conduct secondary analysis of banked data from two rigorous and well-controlled supervised exercise randomized clinical trials (RCTs) and to conduct a 3-year follow-up of >570 participants from both of these RCTs of exercise to assess cognitive, cardiorespiratory fitness, and physical activity levels. In particular, we propose to examine whether exercise-induced changes in cardiometabolic and sleep measures mediate exercise-derived benefits to cognitive and brain outcomes. We will also target moderators of exercise including APOE genotype and racial disparities to better characterize which individual difference variables influence the magnitude of effects of exercise on brain health. Finally, we propose a discovery aim that would leverage our rich measurement of participants at the genetic, physiological, brain, cognitive, and socioemotional levels to perform predictive modeling to forecast long-term adoption of exercise (or barriers prohibiting long-term adoption). In short, this research proposal describes a broad and ambitious line of work that will produce groundbreaking and innovative studies to address significant gaps in our understanding of exercise and brain health in late adulthood. The aims target several major AD/ADRD milestones identified by NIH and will position junior scientists in leadership roles to advance the field forward in significant and pioneering ways.

抽象的 锻炼是最近影响神经认知功能的最有前途的方法之一 成年。但是，目的地这个认可，几个主要的知识差距排除了开处方的能力 锻炼以防止或治疗认知障碍。该R35提案包括一系列创新和 潜在的开创性研究将有助于运动和大脑领域的重大进步 健康。我们在该提案中描述的研究将由几位高度有前途的初级科学家领导 在经验丰富且敬业的精通团队的支持下。概念和科学框架 对于本提案中描述的假设，围绕着锻炼领域面临的三个主要挑战 和认知衰老：（1）我们对运动影响的机制的理解很差 认知功能在成年后期，（2）我们对中等因素或解释的因素的理解很差 个人变化，对运动的反应以及（3）我们不了解预测长期的因素 运动行为的期限采用以及如何减少障碍并增强发现的个人的激励措施 继续锻炼面临挑战。尽管积极的生活方式有明显的好处，但大多数人都无法见面 公共卫生锻炼建议。我们对预测和增强的因素的了解越多 长期采用锻炼，我们对运动是否影响事件的越多 阿尔茨海默氏病和开处方和维护预防运动的最佳实践 认知障碍的治疗。我们建议对两个来自两个的银行数据进行次要分析 严格且控制良好的监督运动随机临床试验（RCT），并进行3年 从这两个练习中的两种RCT中的570名参与者进行随访，以评估认知，心肺 健身和体育锻炼水平。特别是，我们建议检查运动引起的变化 心脏代谢和睡眠测量介导对认知和大脑结果的运动衍生的益处。我们 还将针对运动的主持人，包括APOE基因型和种族差异，以更好地表征 哪些个体差异变量会影响运动对大脑健康的影响的幅度。最后，我们 提案一个发现目标，它将利用我们在遗传上对参与者的丰富度量， 身体，大脑，认知和社会情感水平进行预测建模以预测长期 采用运动（或禁止长期采用障碍）。简而言之，该研究提案描述了 广泛而雄心勃勃的工作将产生开创性和创新研究，以解决重大 我们对成年后期运动和大脑健康的理解的差距。目标针对几个主要 NIH确定的AD/ADRD里程碑，并将初级科学家担任领导角色，以推进该领域 以重要而开创性的方式向前发展。