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

• 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
• 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' s Disease; Alzheimer' 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

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).

项目概要或摘要：阿尔茨海默病（AD）是导致唐氏症成人死亡的主要原因。 在他们的一生中，>90%发展为AD的DS综合征。这可能与异常积累的 淀粉样β蛋白（Aβ）和tau蛋白，与成人DS相比， 在典型发育的成人中发生迟发性散发性AD。典型发育成人的数据 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。目前的美国活动指南表明，定期MVPA通过减少 痴呆症的风险，改善认知，减少睡眠中断，这可能导致约15%的AD 全世界的案例。到目前为止，有限数量的试验已经评估了身体活动与 (PA)部分原因是缺乏这些结果的有效客观指标 在DS人群中。使用ActiGraph便携式加速度计评估PA强度的临界点 腰围是健康相关研究中广泛使用的PA客观指标， 成熟的成年人。然而，典型发育的成年人之间的生物力学和生理差异 和DS成人患者表明，对于典型发育成人验证的ActiGraph强度临界点可能 不适合用于患有DS的成人。我们的初步数据表明，MVPA的临界点约为50% 低于典型发育成人的MVPA临界点。因此，我们可能大大低估了PA 成年人中的DS。该K 01奖项包括2个目标和一个培训计划，以开始解决 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、认知功能和睡眠质量相关的生物标志物。我的短期目标 我的研究和培训计划的重点是：1）为评估开发有效的ActiGraph切割点 2）获得与AD神经病理学相关的知识，包括 血浆生物标志物的评估;和3）发展自由生活睡眠测量的熟练程度， 认知和临床试验的进行相关的PA和AD的成人DS。我的长期目标是 成为一名受资助的研究人员，他是国际公认的了解PA对 成年DS患者的脑老化和AD发展。本K 01的第一个目标是开发和验证免费- 活动ActiGraph GT 9 X Link三轴加速度计活动强度截点，用于久坐、轻度、中度 积极的活动。第二个目的是探讨SB、light PA和MVPA对血浆的影响， 参与NIH的DS成人中与AD、认知功能和睡眠质量相关的生物标志物- 阿尔茨海默氏症生物标志物联盟-唐氏综合征（ABC-DS; U19 AG 070043）研究和生活方式 DS项目中的AD风险（R 01 AG 070028）。