Physical Activity and Dementia: Mechanisms of Action

体力活动和痴呆：作用机制

• 批准号: 10208017
• 负责人: Kirk I Erickson
• 金额: $ 88.26万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 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/10208017
• 关键词: Address; Adoption; Adult; Alzheimer' s Disease; Alzheimer' s disease related dementia; Behavior; Brain; Cognitive; Cognitive aging; Dementia; Exercise; Genetic; Genotype; Impaired cognition; Incentives; Incidence; Individual; Individual Differences; Knowledge; Leadership; Measurement; Measures; Mediating; Mentorship; Methods; Neurocognitive; Ocular orbit; Outcome; Participant; Physical activity; Physiological; Positioning Attribute; Predictive Factor; Prevention; Public Health; Randomized Clinical Trials; Recommendation; Research Proposals; Role; Scientist; Series; Sleep; Supervision; United States National Institutes of Health; Work; active lifestyle; brain health; cardiometabolism; cardiorespiratory fitness; cognitive function; data repository; experience; follow-up; individual variation; innovation; predictive modeling; prevent; racial disparity; 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 运动是影响晚期神经认知功能最有前途的方法之一 然而，尽管有这样的认识，但一些主要的知识差距阻碍了广泛开处方的能力。 该 R35 提案包括一系列创新和治疗认知障碍的运动。 潜在的突破性研究将有助于运动和大脑领域的重大进步 我们在本提案中描述的研究将由几位非常有前途的年轻科学家领导。 在经验丰富且专注的指导团队的支持下，概念和科学框架。 本提案中描述的假设围绕运动领域面临的三大挑战 和认知衰老：（1）我们对运动影响的机制了解甚少 成年晚期的认知功能，（2）我们对调节或解释的因素了解甚少 运动反应的个体差异，以及（3）我们不了解预测长期运动的因素。 锻炼行为的采用以及如何减少障碍并增强对发现的个人的激励 尽管积极的生活方式有明显的好处，但大多数人都无法做到继续锻炼。 我们对预测和增强运动的因素了解得越多。 长期坚持运动，我们就会更加了解运动是否影响发病率 阿尔茨海默病以及为预防和维持运动而制定和维持运动的最佳实践 我们建议对两个存储数据进行二次分析。 严格且控制良好的运动监督随机临床试验（RCT），并进行为期 3 年的研究 对这两项运动随机对照试验中超过 570 名参与者进行随访，以评估认知、心肺功能 特别是，我们建议检查运动是否引起的变化。 心脏代谢和睡眠测量可以调节运动对认知和大脑结果的益处。 还将针对运动调节因素，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程度。 提出一个发现目标，该目标将利用我们对遗传参与者的丰富测量， 生理、大脑、认知和社会情感水平来执行预测建模以预测长期 简而言之，本研究提案描述了一项运动的采用（或阻碍长期采用的障碍）。 广泛而雄心勃勃的工作范围将产生突破性和创新性的研究，以解决重大问题 我们对成年后期运动和大脑健康的理解存在差距，这些目标针对几个主要目标。 NIH 确定了 AD/ADRD 里程碑，并将让年轻科学家担任领导角色，以推动该领域的发展 以重大和开创性的方式向前发展。