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

项目摘要/摘要 这是一份申请以患者为导向的导师研究事业发展奖(K01)的申请书。的目标是 拟议的项目是为候选人提供必要的高级技能，以发展独立的 研究项目的重点是体育活动与认知能力下降和痴呆症之间的联系， 特别是因为它与阿尔茨海默病相关痴呆(ADRD)有关。为了促进这一长期的职业生涯 候选人的目标：专注于两项与体力活动相关的能量消耗指标(“能量学”)(1) 心肺适能和(2)步行的能量成本，作为生理学的客观标志 习惯性体力活动的后果。候选人最近发表的研究表明，衡量 能量学可能最好地捕捉到生理机制潜在的物理有益的影响 认知功能减退风险的活动。这项研究表明，较低的心肺健康水平-- 在持续活动期间向肌肉骨骼系统输送氧气的综合能力-与 认知功能减退，脑萎缩率增加，静息脑血流量下降，说明较高 步行的能量成本--习惯步调步行所需的氧气--与增加几率有关 淀粉样蛋白阳性和加速的海马区和脑萎缩。这个应用程序提出了一个纵向的 研究I)调查能量学变化与认知和阿尔茨海默病的变化的程度 生物标志物，二)评估哪种可修改的能量测量可能具有最大的预测价值 以及iii)研究线粒体作为潜在的潜在生物学基础的功能 能量学-脑联想的机制。有了一个跨学科的指导团队，申请者的职业生涯 发展计划建立在他之前的研究培训的基础上，以熟练掌握以下方面：1)高级神经成像 技术，使用PET和MRS，2)与体力活动相关的能量消耗和运动后测量 MRS评估氧化能力(线粒体功能的相关性)，3)认知变化 老龄化和ADRD，4)纵向统计分析，5)职业发展，6)负责任 进行研究。本次K01奖项的研究目标和培训目标将提供一个学习 促进申请者认知老化和ADRD知识的环境，并促进其过渡到 独立调查人员研究可改变的生活方式活动对老年人认知能力下降的影响 人。

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.