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

项目摘要。阿尔茨海默病及相关痴呆（ADRD）已成为一种主要的公共卫生 危机迄今为止，阿尔茨海默氏病的治疗策略在很大程度上是无效的， 更加注重确定有效的预防战略。每日24小时活动行为（睡眠、身体 活动和久坐时间）可能是ADRD的可改变风险因素。更好地了解这些风险 这些因素可能为早期预防提供了机会，特别是在发病前的无症状阶段。 ADRD相关病理学的发展。纵向腕动计数据客观测量的可用性 24-在一个强ADRD表型的队列中，24小时的活动为研究 24小时活动行为与ADRD之间的潜在途径。本K 01的目标是纵向 研究24小时活动的变化，以及认知、结构神经成像和液体生物标志物的变化 阿尔茨海默病和伴随的病理途径之前，临床痴呆症的发作。我会 利用来自范德比尔特记忆和衰老项目（VMAP）队列的数据， 活动记录仪、脑MRI和阿尔茨海默病神经病理学和伴随损伤的流体生物标志物。的 该提议的中心假设是24小时活动的变化将与认知能力下降相关， 结构神经影像学变化，阿尔茨海默病和伴随的通路变化， 症状发作。基于这一假设，该提案旨在1）描述变化之间的关联 在24小时活动和认知能力下降中，2）检查24小时活动与MRI标记物相关的变化， 神经变性和小血管疾病，和3）评估24小时活动行为的变化与流体 阿尔茨海默病神经病理学和伴随途径的生物标志物。综合起来，这些目标将 联合收割机将24小时活动的客观测量与认知、神经影像学和最新技术水平的流体相结合 生物标志物数据，以填补现有的研究空白。同时，在整个奖项，候选人将 获得1）阿尔茨海默病病理生理学和流行病学的高级培训; 2）测量和 阿尔茨海默病神经病理学和伴随通路的结构成像和流体生物标志物的建模 3）先进的统计方法，使候选人成为以下领域的领导者： 老龄化和阿尔茨海默病流行病学。范德比尔特大学医学中心和范德比尔特记忆 和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 活动本K 01的总体目标是告知一系列R 01奖项和独立研究计划 专注于识别和描述ADRD的行为风险因素。在K 01奖项的支持下， 和专家指导，候选人将实现这一目标，并成功地过渡到独立 培训期结束时的研究者状态。

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.