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

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.

摘要 运动是最有前途的积极影响神经认知功能的方法之一， 成年然而，尽管认识到这一点，一些主要的知识差距妨碍了广泛规定的能力， 运动以预防或治疗认知障碍。这一R35提案包括一系列创新和 潜在的突破性研究，将有助于在运动和大脑领域的重大进展 健康我们在本提案中描述的研究将由几位非常有前途的初级科学家领导 在一个经验丰富和敬业的导师团队的支持下。概念和科学框架 因为本建议中所描述的假设围绕着演习领域面临的三个主要挑战 和认知老化：（1）我们对运动影响认知老化的机制缺乏了解， 成年后期的认知功能，（2）我们对调节或解释这些因素的因素缺乏了解， 个体差异，对运动的反应，和（3）我们不知道预测长期- 长期采用的锻炼行为，以及如何减少障碍，提高激励个人谁发现 继续锻炼很有挑战性。尽管积极的生活方式有明显的好处，但大多数人都没有达到 公共健康建议运动。我们对预测和增强的因素了解得越多 长期接受锻炼，我们就越了解锻炼是否会影响 阿尔茨海默病和处方和维持运动的预防和治疗的最佳实践 认知障碍的治疗。我们建议对来自两个国家的银行数据进行二次分析。 严格和良好控制的监督运动随机临床试验（RCT），并进行为期3年的 对来自这两项运动随机对照试验的>570名参与者进行随访，以评估认知、心肺功能、 健康和身体活动水平。特别是，我们建议检查运动引起的变化是否 心脏代谢和睡眠测量介导运动对认知和大脑结果的益处。我们 还将针对包括APOE基因型和种族差异在内的运动调节因素，以更好地表征 哪些个体差异变量影响运动对大脑健康影响的大小。最后我们 提出一个发现的目标，将利用我们丰富的测量参与者在遗传， 生理、大脑、认知和社会情感水平，以执行预测建模， （3）采用运动（或阻碍长期采用的障碍）。简而言之，这项研究提案描述了一个 广泛而雄心勃勃的工作路线，将产生开创性和创新性的研究，以解决重大 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的 由NIH确定的AD/ADRD里程碑，并将使初级科学家担任领导角色，以推动该领域的发展 以重要和开拓性的方式前进。

项目成果

Physical Performance and Amyloid-β in Humans: A Systematic Review and Meta-Analysis of Observational Studies.

人类的身体表现和淀粉样蛋白-β：观察研究的系统回顾和荟萃分析。

• DOI: 10.3233/jad-230586
• 发表时间: 2023
• 期刊: Journal of Alzheimer's disease : JAD
• 作者: Solis-Urra,Patricio;Rodriguez-Ayllon,María;Álvarez-Ortega,Miriam;Molina-Hidalgo,Cristina;Molina-Garcia,Pablo;Arroyo-Ávila,Cristina;García-Hermoso,Antonio;Collins,AudreyM;Jain,Shivangi;Gispert,JuanDomingo;Liu-Ambrose,Teresa;Ortega,
• 通讯作者: Ortega,