Physical activity over the adult life course and cognitive resilience to Alzheimer's disease and related dementias

项目摘要/摘要 由Phillip Hwang博士、公共卫生硕士Phillip Hwang博士领导的这项K01提案考察了体力活动作为贡献者的作用 在成年后的整个生命过程中的认知韧性。体力活动越多，认知能力越好。 功能，降低阿尔茨海默病和相关痴呆(ADRD)的风险。体力活动被认为是 通过促进神经补偿来发挥其对大脑的潜在有益影响，包括改变 支持更大的大脑效能和能力的结构和功能大脑特征。因此，物理上 刺激可能是认知韧性的关键因素，认知韧性被认为是承受能力 更大的ADRD风险水平，避免认知障碍或具有好于预期的认知功能。 关于体力活动作为潜在复原力因素的知识的一个主要差距是， 在整个生命过程中，身体活动对韧性的影响是不同的。证据也缺乏具体的方面 体力活动与认知韧性相关的体力活动，如频率或活动类型致信地址 这些知识差距，这项建议将重点放在成年早期、中年和晚年的体力活动和 使用复杂的基于统计和机器学习的方法评估他们与认知韧性之间的关联 方法：研究方法。体力活动数据收集自弗雷明翰心脏研究(FHS)，该研究有参与者 在一生中登记并进行痴呆症监测，包括神经心理检查， 会支持这项调查。来自可穿戴设备的额外多维身体活动数据将 来自于精准脑健康优化综合数字技术平台项目。 研究计划得到了波士顿大学卓越的指导团队和培训计划的补充 大学医学院，将提供丰富的培训环境，将培养黄博士的 发展成为独立的研究人员。该计划建立在黄博士在 神经流行病学和ADRD预防研究，并包括新的体能测量培训 与ADRD有关的活动、神经成像和认知评估，以及机器学习方法。这个 联合研究和培训计划将为黄博士成功的独立研究生涯做好准备 专注于确定生命过程中可更改的生活方式因素，并设计多领域的生活方式 促进大脑健康老化和延缓或可能预防ADRD发病的干预措施。 这项研究与NIA 2020-2025年的战略研究方向保持一致，以确定 行为、心理和神经机制和过程赋予成功的衰老和韧性 与认知障碍有关。随着老年人数量的增长，这项研究是迫切需要的 这意味着ADRD的新病例数量也将增加，因为老龄化本身仍然是最严重的 ADRD的重要风险因素。这项研究的发现将有助于提供可以作为 为ADRD制定与体力活动有关的预防性干预措施的基础。

PROJECT SUMMARY/ABSTRACT This K01 proposal, led by Dr. Phillip Hwang, PhD, MPH, examines the role of physical activity as a contributor to cognitive resilience across the adult life course. Greater physical activity is associated with better cognitive function and reduced risk for Alzheimer’s disease and related dementias (ADRD). Physical activity is thought to exert its potential beneficial effects on the brain by promoting neural compensation, including changes to structural and functional brain characteristics that support greater brain efficacy and capacity. Thus, physical stimulation may be a key contributor to cognitive resilience, which is considered as the ability to withstand greater ADRD risk levels and avoid cognitive impairment or have better-than-expected cognitive function. A major gap in knowledge regarding physical activity as a potential resilience factor is whether the impact of physical activity on resilience differs across the life course. Evidence is also lacking on specific aspects of physical activity, such as frequency or type of activity, that correlate with cognitive resilience. To address these knowledge gaps, this proposal will focus on physical activity in early adult life, midlife, and late-life and evaluate their associations with cognitive resilience using sophisticated statistical- and machine learning-based methods. Physical activity data collected from the Framingham Heart Study (FHS), which has participants enrolled across the lifespan and conducts dementia surveillance, including neuropsychological examinations, will support this investigation. Additional multi-dimensional physical activity data from wearable devices will come from the Integrated Digital Technology Platform for Optimization of Precision Brain Health project. The research plan is complemented by an exceptional mentorship team and training plan at the Boston University School of Medicine, which will provide a rich training environment that will foster Dr. Hwang’s development into an independent researcher. The plan builds on the Dr. Hwang’s background in neuroepidemiology and ADRD prevention research, and includes new training in the measurement of physical activity, neuroimaging and cognitive assessments in relation to ADRD, and machine learning methods. The combined research and training plans will prepare Dr. Hwang for a successful independent research career focused on identifying modifiable lifestyle factors over the life course and designing multi-domain lifestyle interventions to promote healthy brain aging and delay or possibly prevent the onset of ADRD. This research aligns with the NIA’s Strategic Directions for Research, 2020-2025 key goals to identify the behavioral, psychological, and neural mechanisms and processes that confer successful aging and resilience to cognitive impairment. This research is urgently needed as the number of older adults is growing, which means that the number of new cases of ADRD will increase as well, given that aging itself remains the most significant risk factor for ADRD. Findings from this research will help provide knowledge that can serve as the basis for the development of preventive interventions related to physical activity for ADRD.