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

阿尔茨海默病的能量消耗、认知功能和生物标志物特征

• 批准号: 10572262
• 负责人: Ryan James Dougherty
• 金额: $ 12.61万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-15 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10572262
• 关键词: Acceleration; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid; Baltimore; Biological; Biological Markers; Brain; Cerebrovascular Circulation; Clinical Research; Cognition; Cognitive; Cognitive aging; Data; Dementia; Development; Development Plans; Diagnostic; Dimensions; Disease; Disease Progression; Elderly; Energy Metabolism; Exercise; Genetic; Genotype; Goals; Impaired cognition; Individual; Intervention; Knowledge; Life Style; Link; Literature; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentored Research Scientist Development Award; Mentorship; Mitochondria; Muscle Mitochondria; Musculoskeletal System; Outcome; Oxygen; Pharmaceutical Preparations; Physical activity; Physiological; Positron-Emission Tomography; Predictive Value; Publishing; Research; Research Personnel; Research Proposals; Research Training; Rest; Risk; Risk Assessment; Risk Reduction; Role; Skeletal Muscle; Specificity; Statistical Data Interpretation; Techniques; Therapeutic; Time; Training; Translational Research; Walking; Work; apolipoprotein E-4; brain volume; cardiorespiratory fitness; career; career development; cerebral atrophy; cognitive change; cognitive function; cognitive performance; cohort; cost; educational atmosphere; hippocampal atrophy; insight; lifestyle factors; mild cognitive impairment; neuroimaging; novel; programs; prospective; research study; responsible research conduct; sex; skills; specific biomarkers; tau Proteins; tau aggregation; walking speed

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.

项目概要/摘要 这是指导患者导向研究职业发展奖 (K01) 的申请。目标是 拟议的项目旨在为候选人提供发展独立能力所需的高级技能 研究计划的重点是体力活动与认知能力下降和痴呆症之间的关联， 特别是与阿尔茨海默病相关的痴呆症 (ADRD) 相关。为了促进这一长期职业生涯 候选人将实现的目标： 重点关注两种与身体活动相关的能量消耗指标（“能量学”）(1) 心肺健康和（2）步行的能量消耗，作为生理指标的客观指标 习惯性体力活动的后果。候选人最近发表的作品表明， 能量学可以最佳地捕捉物理有益影响背后的生理机制 认知能力下降风险的活动。这项研究表明，心肺健康水平较低 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（习惯节奏步行所需的氧气）与增加的几率相关 淀粉样蛋白阳性并加速海马和脑萎缩。本申请提出了纵向 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) 评估哪种可修改的能量测量可能具有最大的预测价值 对于上述结果； iii) 研究线粒体功能作为潜在的生物学基础 能量-大脑关联的机制。拥有跨学科的导师团队，申请人的职业生涯 发展计划建立在他之前的研究培训的基础上，以熟练掌握：1）高级神经影像学 技术，使用 PET 和 MRS，2) 与身体活动相关的能量消耗和运动后测量 MRS 氧化能力评估（与线粒体功能相关），3) 相关认知变化 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K01奖的研究目标和培养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，并促进他过渡到 独立调查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。