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

项目摘要或摘要：阿尔茨海默病(AD)是成人唐氏综合症患者的主要死亡原因 综合征(DS)，90%的人在其一生中发展为阿尔茨海默病。这可能与非正常堆积有关。 淀粉样β蛋白(Aβ)和tau蛋白在成人DS患者中出现的时间比 在典型发育的成人中发生迟发性散发性阿尔茨海默病。来自典型成年人的数据 建议久坐行为(SB)和低强度到中等强度的体力活动(MVPA)有关 约占AD的12%。目前美国的活动指南表明，定期的MVPA通过减少 患痴呆症的风险、改善认知和减少睡眠中断可能导致约15%的阿尔茨海默病 世界各地的病例。到目前为止，只有有限数量的试验评估了体力活动之间的联系 (PA)成人DS患者的强度和AD，部分原因是缺乏对这些结果的有效客观测量 在DS人群中。使用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的客观测量标准，已被开发用于典型的 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 患有DS的成年人建议，对于典型的发育成熟的成年人来说，活动强度的临界点可能是 不适合成人DS患者使用。我们的初步数据显示，MVPA的临界点为~50% 低于正常成人的MVPA临界点。因此，我们可能大大低估了PA 成人DS患者的血药浓度。这一K01奖项包括两个目标和一个培训计划，以开始解决 日常生活活动强度的评估及PA强度和持续时间对血浆的影响 与阿尔茨海默病、认知功能和睡眠质量相关的生物标记物。我的短期目标 我的研究和培训计划的重点是：1)为评估制定有效的活动图切入点 对患有DS的成人进行日常PA的评估；2)获取与AD的神经病理相关的知识，包括 评估血浆生物标记物；以及3)熟练测量自由生活睡眠和 成人DS患者与PA和AD相关的认知和临床试验的进行。我的长期目标是 成为一名获得资助的调查员，他是国际公认的了解PA对以下方面影响的专家 成年DS患者的脑老化与阿尔茨海默病的发展此K01的第一个目标是开发和验证免费- Living Actigraph GT9X Link三轴加速度计活动强度分界点：久坐、轻度、中度、 精力充沛的运动。第二个目的是探讨SB、LIGHT PA和MVPA对血浆的影响 与AD、认知功能和睡眠质量相关的生物标记物在患有DS的成年人中参与NIH- 资助的阿尔茨海默病生物标记物联合唐氏综合症(ABC-DS；U19 AG070043)研究和生活方式 DS项目中的AD风险(R01 AG070028)。

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).