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.

项目摘要/摘要