Assessment of Physical Activity for Alzheimer's Disease Research in Down Syndrome

唐氏综合症阿尔茨海默病研究的体力活动评估

基本信息

批准号：
10722771
负责人：
Brian Helsel
金额：
$ 12.5万
依托单位：
UNIVERSITY OF KANSAS 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：
2023-09-01 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10722771
关键词：
Accelerometer Address Adult Alzheimer&apos s Disease Alzheimer&apos s disease risk Alzheimer’s disease biomarker Amyloid beta-Protein Award Biological Markers Biomechanics Cause of Death Cognition Conduct Clinical Trials Data Data Analyses Development Down Syndrome Fostering Funding Future Goals Guidelines Health High Prevalence Hip region structure Indirect Calorimetry Individual Infrastructure International Investments Kansas Knowledge acquisition Lead Learning Life Life Style Light Link Location Measurement Measures Mentored Research Scientist Development Award Mentors Mentorship Metabolic Outcome Outcome Measure Participant Physical activity Physical assessment Physiological Plasma Population Process Receiver Operating Characteristics Research Research Activity Research Personnel Risk Reduction Sampling Scientist Sleep Sleep disturbances Strenuous Exercise Training United States National Institutes of Health Universities Validation Walking Wrist abeta accumulation actigraphy aging brain brain health career cognitive function dementia risk experience improved moderate-to-vigorous physical activity multidisciplinary neuropathology portability prevent secondary analysis sedentary sedentary lifestyle sleep quality tau Proteins treadmill

项目摘要

Project Summary or Abstract: Alzheimer’s disease (AD) is the leading cause of death in adults with Down syndrome (DS) with >90% developing AD in their lifetime. This may be related to the abnormal accumulation of amyloid beta (Aβ) and tau proteins which occur 20-30 years earlier in adults with DS compared with the development of late-onset sporadic AD in typically developed adults. Data from typically developed adults suggest that sedentary behavior (SB) and low moderate-to-vigorous physical activity (MVPA) are associated with ~12% of AD. Current U.S. activity guidelines suggest that regular MVPA benefits brain health by reducing the risk of dementia, improving cognition, and reducing sleep disruptions which may contribute to ~15% of AD cases worldwide. To date, a limited number of trials have evaluated the association between physical activity (PA) intensity and AD in adults with DS due in part to a lack of validated objective measures of these outcomes in the DS population. Cut-points to assess PA intensity using the ActiGraph portable accelerometer worn at the waist, a widely used objective measure of PA in health-related research, have been developed for typically developed adults. However, biomechanical and physiological differences between typically developed adults and adults with DS suggest that ActiGraph intensity cut-points validated for typically developed adults may be inappropriate for use in adults with DS. Our preliminary data suggests that the cut-point for MVPA is ~50% lower than the MVPA cut-point for typically developed adults. Thus, we may be vastly underestimating PA levels in adults with DS. This K01 award consists of 2 aims and a training plan to begin to address the assessment of activity intensity during daily life and the impact of PA intensity and duration on plasma biomarkers associated with AD, cognitive function, and sleep quality in adults with DS. My short-term goals and the focus of my research and training plan are to: 1) develop valid ActiGraph cut-points for the assessment of daily PA in adults with DS; 2) acquire knowledge related to the neuropathology of AD including the assessment of plasma biomarkers; and 3) develop proficiency in the measurement of free-living sleep and cognition and the conduct of clinical trials relative to PA and AD in adults with DS. My long-term goal is to become a funded investigator who is an internationally recognized expert in understanding the impact of PA on brain aging and AD development in adults with DS. The first aim of this K01 is to develop and validate free- living ActiGraph GT9X Link triaxial accelerometer activity intensity cut-points for sedentary, light, moderate, and vigorous activity. The second aim is to explore the impact of SB, light PA, and MVPA on plasma biomarkers associated with AD, cognitive function, and sleep quality in adults with DS participating in the NIH- funded Alzheimer’s Biomarker Consortium - Down Syndrome (ABC-DS; U19 AG070043) study and Lifestyle and AD risk in DS project (R01 AG070028).

项目摘要或摘要：阿尔茨海默病 (AD) 是成人唐氏病患者死亡的主要原因超过 90% 的人在一生中患有 AD 综合征（DS），这可能与 AD 的异常积累有关。与普通 DS 患者相比，β 淀粉样蛋白 (Aβ) 和 tau 蛋白的出现早 20-30 年典型发育成人迟发性散发性 AD 的发展数据来自典型发育成人。表明久坐行为（SB）和低中度至剧烈体力活动（MVPA）相关约 12% 的 AD 活动指南表明，定期 MVPA 通过减少降低患痴呆症的风险、改善认知能力并减少睡眠中断（这些因素可能导致约 15% 的 AD）迄今为止，只有少数试验评估了身体活动之间的关联。成人 DS 患者的 (PA) 强度和 AD 部分原因是缺乏对这些结果进行有效客观测量使用佩戴在 DS 人群中的 ActiGraph 便携式加速度计评估 PA 强度的切点。腰围是健康相关研究中广泛使用的 PA 客观测量指标，已被开发用于典型的然而，典型发育的成年人之间存在生物力学和生理差异。患有 DS 的成人表明，针对典型发育成人验证的 ActiGraph 强度切点可能是不适合用于患有 DS 的成人。我们的初步数据表明 MVPA 的切点约为 50%。低于正常发育成人的 MVPA 切点因此，我们可能大大低估了 PA。该 K01 奖项由 2 个目标和一个开始解决 DS 的培训计划组成。评估日常生活中的活动强度以及PA强度和持续时间对血浆的影响与 AD、认知功能和 DS 成人睡眠质量相关的生物标志物。我的研究和培训计划的重点是：1）开发有效的 ActiGraph 评估切点 DS 成人每日 PA 的频率；2) 获取与 AD 神经病理学相关的知识，包括评估血浆生物标志物；3) 提高测量自由生活睡眠和我的长期目标是对患有 DS 的成人进行与 PA 和 AD 相关的认知和临床试验。成为一名受资助的调查员，他是国际公认的专家，了解 PA 对人的影响患有 DS 的成人的大脑老化和 AD 发展该 K01 的首要目标是开发和验证自由- 生活 ActiGraph GT9X Link 三轴加速度计活动强度切点，适用于久坐、轻度、中度、第二个目的是探讨 SB、轻 PA 和 MVPA 对血浆的影响。参与 NIH 的 DS 成人患者与 AD、认知功能和睡眠质量相关的生物标志物资助阿尔茨海默病生物标志物联盟 - 唐氏综合症（ABC-DS；U19 AG070043）研究和生活方式 DS 项目（R01 AG070028）中的 AD 风险。