Lifestyle Risk and Resiliency Factors and Alzheimer’s Disease in Down syndrome

项目摘要 本行政副刊是根据国家卫生研究院资助项目的国家卫生监督管理局的要求提交的 综合征(DS)研究目标与美国国立卫生研究院在全国范围内的共生疾病调查相关 了解唐氏综合症的寿命(包括)项目(非-OD-20-024)。患有DS的成年人处于高危状态 治疗由21三体引起的阿尔茨海默病。然而，早发症的发病年龄有明显的差异。 阿尔茨海默病病理与DS临床痴呆发病年龄的关系。父R01的目标是 考察四种生活方式因素的影响--身体活动、睡眠、认知刺激和社交 介入-AD的影像和生物流体生物标记物、认知功能减退和临床AD状态 DS.家长R01包括三个研究站点，并登记了140名患有DS的成年人，他们也参加了NIH- 资助DS中的阿尔茨海默氏症生物标记物联盟(ABC-DS；U19 AG070043)。行政管理的目标 补充是通过增加样本数量来加强亲本R01，同时也通过增加样本社会- 人口多样性。这个更大、更多样化的样本将被用来进行新的调解 分析以阐明生活方式因素与DS中AD之间的路径。这份补充文件还旨在 测试先进的加速度计数据分析方法作为睡眠和生理的非侵入性生物标记物 DS中的活动。为了实现这些目标，补充方案包括招募另外40名患有DS的成年人加入 家长R01包括一个新的研究地点(加州大学欧文分校)。生活方式数据将在以下时间收集 这一新的群体在某个时间点。关于身体健康、睡眠、认知刺激和社交的信息 参与度将使用自我/信息报告和客观测量(Actigraph和WatchPAT)收集。 生活方式因素的数据收集将与AD生物标志物的ABC-DS数据收集(PET)及时对应 β，PET tau，PET FDG，结构和功能磁共振，脑脊液Aβ和tau，和血液)，认知功能， 以及痴呆症的症状和状态。行政副刊的具体目的是：1)增加 ABC-DS参与者的数量和社会人口多样性(地理位置、种族和年龄) 加入父母R01；2)测试生活方式因素影响路径的中介模型 DS患者的AD病理、认知功能减退和向MCI和AD痴呆转变的时间； 比较作为体力活动生物标志物的加速度计数据的处理和分析策略 患有DS的成年人的睡眠障碍。附录中的信息将有助于确定生活方式是否是一种 延缓成年DS患者阿尔茨海默病的重要可修改的弹性机制。

Project Summary This administrative supplement is submitted in response to the NOSI for funded projects to meet NIH Down Syndrome (DS) research objectives related to NIH’s Investigation of Co-occurring conditions across the Lifespan to Understand Down syndrome (INCLUDE) project (NOT-OD-20-024). Adults with DS are at high risk for Alzheimer’s disease (AD) due to trisomy 21. However, there is marked variability in the age of onset of early Alzheimer’s disease pathology and age of onset of clinical dementia in DS. The goal of the parent R01 is to examine the effect of four lifestyle factors – physical activity, sleep, cognitive stimulation, and social engagement – on imaging and biofluid biomarkers of AD, cognitive decline, and clinical AD status in adults with DS. The parent R01 includes three study sites and enrolls 140 adults with DS who are also enrolled in the NIH- funded Alzheimer’s Biomarker Consortium in DS (ABC-DS; U19 AG070043). The goal of the administrative supplement is to strengthen the parent R01 by increase sample number but also by increasing sample socio- demographic diversity. This larger and more diverse sample will then be leveraged to conduct new mediational analyses to elucidate pathways between lifestyle factors and AD in DS. The supplement is also aimed at testing advanced analytic methods for accelerometer data as a non-invasive biomarker of sleep and physical activity in DS. To accomplish these goals, the supplement involves enrolling 40 additional adults with DS into the parent R01 by including a new study site (University of California-Irvine). Lifestyle data will be collected on this new cohort at one time point. Information on physical health, sleep, cognitive stimulation, and social engagement will be collected using self/informant report and objective measures (actigraph and WatchPAT). Data collection of lifestyle factors will correspond in time with ABC-DS data collection of AD biomarkers (PET Aβ, PET tau, PET FDG, structural and functional MRI, and CSF Aβ and tau, and blood), cognitive functioning, and dementia symptoms and status. The specific aims of the administrative supplement are to: 1) Increase the number and sociodemographic diversity (geographical location, race, and age) of participants from ABC-DS enrolled in the parent R01; 2) Test mediational models of the pathways through which lifestyle factors influence AD pathology, cognitive decline and the timing of the transition to MCI and AD dementia in DS; and 3) Compare strategies for processing and analyzing accelerometer data as a biomarker of physical activity and sleep disruptions in adults with DS. Information from the supplement will help determine if lifestyle is an important modifiable resiliency mechanism for delaying AD in adults with DS.