Energy expenditure, cognitive function, and biomarker features of Alzheimer's disease

项目总结/摘要 这是一个指导病人为导向的研究职业发展奖（K 01）的应用程序。的目标 拟议的项目是为候选人提供必要的先进技能，以发展一个独立的 一项研究计划集中在身体活动与认知能力下降和痴呆症之间的联系， 特别是涉及阿尔茨海默病相关痴呆（ADRD）时。为了促进这一长期的职业生涯 目标候选人将：专注于两个与体力活动相关的能量消耗指标（“能量学”）（1） 心肺适应性和（2）步行的能量消耗，作为生理指标的客观标志。 习惯性体力活动的后果。候选人最近发表的工作表明， 能量学可以最佳地捕获物理的有益效果的生理机制， 活动对认知能力下降的风险。这项研究表明，较低水平的心肺健康- 在持续活动期间向肌肉骨骼系统输送氧气的综合能力-与 认知能力下降，脑萎缩率增加，静息脑血流量减少， 步行的能量消耗--习惯步速步行所需的氧气--与增加的几率有关 淀粉样蛋白阳性加速海马和脑萎缩本申请提出了一种纵向 研究i）调查能量学变化与认知和AD变化的跟踪程度 生物标志物，ii）评估哪一种可修改的能量测量可以对以下方面保持最大的预测值： 上述结果;和iii）研究线粒体功能作为潜在的潜在生物学基础 能量-大脑关联的机制。通过跨学科的导师团队，申请人的职业生涯 发展计划建立在他以前的研究培训，以获得熟练程度：1）先进的神经成像 技术，使用PET和MRS，2）能量消耗和运动后的身体活动相关措施 氧化能力的MRS评估（线粒体功能的相关性），3）相关的认知变化 与老龄化和ADRD，4）纵向统计分析，5）专业发展，6）负责 进行研究。本次K 01奖的研究目标和培训目标将提供一个学习 环境，以提高申请人在认知老化和ADRD方面的知识，并促进他向 独立调查员检查可改变的生活方式活动对老年人认知能力下降的影响 人士

PROJECT SUMMARY / ABSTRACT This is an application for a Mentored Patient-Oriented Research Career Development Award (K01). The goal of the proposed project is to provide the candidate with advanced skills necessary to develop an independent research program focused on the association between physical activity and cognitive decline and dementia, particularly as it pertains to Alzheimer disease-related dementias (ADRDs). To facilitate this long-term career goal the candidate will: focus on two physical activity-related measures of energy expenditure (“energetics”) (1) cardiorespiratory fitness and (2) the energetic cost of walking, as objective markers of the physiological consequences of habitual physical activity. Recent published work by the candidate suggests that measures of energetics may optimally capture the physiological mechanisms underlying the beneficial effects of physical activity on risk for cognitive decline. This research indicates that lower levels of cardiorespiratory fitness –the integrated ability to deliver oxygen to the musculoskeletal system during sustained activity– is associated with cognitive decline, increased rate of brain atrophy, and decreased resting cerebral blood flow and that a higher energetic cost of walking –the oxygen needed for customary paced walking– is associated with increased odds of amyloid positivity and accelerated hippocampal and brain atrophy. This application proposes a longitudinal study to i) investigate the extent to which changes in energetics track with changes in cognition and AD biomarkers, ii) assess which modifiable energetic measure may hold the greatest predictive value with respect to the forgoing outcomes; and iii) investigate mitochondrial function as a potential underlying biological mechanism of energetics-brain associations. With a transdisciplinary mentorship team, the applicants career development plan builds on his previous research training to gain proficiency in: 1) advanced neuroimaging techniques, using PET and MRS, 2) physical activity-related measures of energy expenditure and post-exercise MRS assessment of oxidative capacity (a correlate of mitochondrial function), 3) cognitive changes associated with aging and ADRD, 4) longitudinal statistical analysis, 5) professional development, and 6) responsible conduct of research. The research objectives and training goals of this K01 award will provide a learning environment to advance the applicants knowledge in cognitive aging and ADRD and facilitate his transition to an independent investigator examining the impact of modifiable lifestyle activities on cognitive decline in older persons.