The role of 24-hour activity in Alzheimer's Disease

24 小时活动在阿尔茨海默病中的作用

基本信息

批准号：
10723684
负责人：
Kelsie Marie Full
金额：
$ 12.02万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-15 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10723684
关键词：
Academic Medical Centers Adult Age Aging Alzheimer associated neurodegeneration Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease pathology Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Alzheimer’s disease biomarker Amyloid beta-Protein Award Behavior Behavioral Biological Markers Blood - brain barrier anatomy Cerebrospinal Fluid Clinical Cognition Cognitive Cross-Sectional Studies Data Dementia Development Elderly Environment Epidemiology Functional disorder Goals Growth Hippocampus Hour Impaired cognition Injury Life Style Light Link Liquid substance Magnetic Resonance Imaging Measurement Measures Memory Mentored Research Scientist Development Award Mentorship Microvascular Dysfunction Modeling Nature Nerve Degeneration Pathologic Pathology Pathway interactions Phase Phenotype Physical activity Plasma Platelet-Derived Growth Factor beta Receptor Positioning Attribute Prevention Prevention strategy Public Health Research Research Activity Research Design Research Personnel Risk Factors Role Series Sleep Statistical Methods Structural Models Sum Symptoms Synapses Theoretical model Therapeutic Time Training Training Activity White Matter Hyperintensity Work actigraphy axon injury brain magnetic resonance imaging cohort dementia risk imaging biomarker improved in vivo magnetic resonance imaging biomarker modifiable risk neurofilament neurogranin neuroimaging neuroimaging marker neuroinflammation neuropathology poor sleep programs sedentary structural imaging tau Proteins tau-1 treatment strategy

项目摘要

PROJECT SUMMARY. Alzheimer’s disease and related dementias (ADRD) has become a major public health crisis. To date, therapeutic strategies for Alzheimer’s disease have been largely ineffective resulting in an increased focus on identifying effective prevention strategies. Daily 24-hour activity behaviors (sleep, physical activity, and sedentary time) may be modifiable risk factors for ADRD. A better understanding of these risk factors may provide an opportunity for early prevention, particularly in the asymptomatic phase prior to the development of ADRD-related pathology. The availability of longitudinal actigraphy data to objectively-measure 24-hour activity in a strongly ADRD-phenotyped cohort has created the ideal opportunity to investigate potential pathways linking 24-hour activity behaviors with ADRD. The objective of this K01 is to longitudinally investigate changes in 24-hour activity with changes in cognition, structural neuroimaging, and fluid biomarkers of Alzheimer’s disease and concomitant pathological pathways prior to the onset of clinical dementia. I will leverage data from the Vanderbilt Memory and Aging Project (VMAP) cohort with repeated measures of actigraphy, brain MRI, and fluid biomarkers of Alzheimer’s disease neuropathology and concomitant injury. The central hypothesis of this proposal is changes in 24-hour activity will be associated with cognitive decline, structural neuroimaging changes, and Alzheimer’s disease and concomitant pathway changes, preceding symptom onset. Based on this hypothesis, the proposal aims to 1) characterize associations between changes in 24-hour activity and cognitive decline, 2) examine changes in 24-hour activity in relation to MRI markers of neurodegeneration and small vessel disease, and 3) evaluate changes in 24-hour activity behaviors with fluid biomarkers of Alzheimer’s disease neuropathology and concomitant pathways. Taken together, these aims will combine objective measurement of 24-hour activity with cognitive, neuroimaging, and state of the art fluid biomarker data to fill existing gaps in the research. Simultaneously, throughout the award, the candidate will gain advanced training in 1) Alzheimer’s disease pathophysiology and epidemiology; 2) measurement and modeling of structural imaging and fluid biomarkers of Alzheimer’s neuropathology and concomitant pathways of injury; and 3) advanced statistical methods, positioning the candidate to become a leader in the fields of aging and Alzheimer’s disease epidemiology. Vanderbilt University Medical Center and the Vanderbilt Memory and Alzheimer’s Center provide the ideal environment to complete the proposed research and training activities. The overall goal of this K01 is to inform a series of R01 awards and independent research program focused on identifying and characterizing behavioral risk factors for ADRD. With the support of this K01 award and expert mentorship, the candidate will achieve this goal and successfully transition to independent investigator status by the conclusion of the training period.

项目摘要。阿尔茨海默氏病和相关痴呆症（ADRD）已成为主要的公共卫生危机。迄今为止，阿尔茨海默氏病的理论策略在很大程度上无效，导致增加专注于确定有效的预防策略。每日24小时的活动行为（睡眠，身体活动和久坐时间）可能是ADRD的可修改风险因素。更好地理解这些风险因素可能为早期预防提供机会，尤其是在无症状阶段与ADRD相关的病理的发展。纵向行为摄影数据的可用性以客观衡量 24小时的活动在强烈的ADRD型人群中，为调查创造了理想的机会将24小时活动行为与ADRD联系起来的潜在途径。该K01的目的是纵向研究24小时活动的变化，认知，结构神经影像和流体生物标志物的变化临床痴呆发作之前，阿尔茨海默氏病和伴随的病理途径。我会利用范德比尔特记忆和老化项目（VMAP）队列的数据，并重复衡量阿尔茨海默氏病神经病理学和伴随损伤的动作学，大脑MRI和液体生物标志物。该建议的中心假设是24小时活动的变化将与认知能力下降有关，结构性神经成像变化，阿尔茨海默氏病和伴随途径变化，此前症状发作。基于此假设，该提案的目的是1）表征变化之间的关联在24小时的活动和认知下降中，2）检查与24小时活动的变化相对于MRI标记神经变性和小血管疾病，3）评估流体24小时活动行为的变化阿尔茨海默氏病神经病理学和伴随途径的生物标志物。两者一起，这些目标将将24小时活性的客观测量与认知，神经影像和最先进的状态相结合生物标志物数据以填补研究中的现有空白。同时，在整个奖项中，候选人将在1）阿尔茨海默氏病的病理生理学和流行病学中获得高级培训； 2）测量和阿尔茨海默氏神经病理学和伴随途径的结构成像和流体生物标志物的建模受伤； 3）高级统计方法，将候选人定位为成为领域的领导者衰老和阿尔茨海默氏病流行病学。范德比尔特大学医学中心和范德比尔特的记忆阿尔茨海默氏症中心提供了理想的环境，以完成拟议的研究和培训活动。该K01的总体目标是为一系列R01奖和独立研究计划提供信息专注于识别和表征ADRD的行为风险因素。在该K01奖的支持下和专家精神制，候选人将实现这一目标，并成功过渡到独立调查人员的状态通过培训期的结论。