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

唐氏综合症中的生活方式风险和弹性因素以及阿尔茨海默病

• 批准号: 10669953
• 负责人: Sigan L Hartley
• 金额: $ 23.47万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669953
• 关键词: Abeta synthesis; Accelerometer; Address; Administrative Supplement; Adult; Age; Age of Onset; Algorithms; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-42; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Area; Award; Biological Markers; Blood; Brain; California; Chromosome 21; Clinical; Cognitive; Computer software; Data; Data Collection; Dementia; Devices; Down Syndrome; Enrollment; Equation; Functional Magnetic Resonance Imaging; Funding; Gene Proteins; Geographic Locations; Goals; Head; Hippocampus; Hispanic; Image; Impaired cognition; Individual; Intervention; Investigation; Laos; Leisures; Life; Life Style; Link; Longevity; Measures; Mediation; Memory Loss; Methods; Modeling; Parents; Participant; Pathology; Pathway Analysis; Pathway interactions; Physical activity; Population; Populations at Risk; Positron-Emission Tomography; Prevention; Public Health; Race; Reporting; Research; Risk Factors; Sample Size; Sampling; Shapes; Site; Sleep; Sleep Apnea Syndromes; Sleep Fragmentations; Sleep disturbances; Social Policies; Structure; Symptoms; Testing; Time; United States National Institutes of Health; Universities; Wrist; abeta accumulation; actigraphy; advanced analytics; aged; analytical method; autosomal dominant Alzheimer' s disease; brain metabolism; cerebrovascular; cognitive function; cohort; cost; extracellular; glucose metabolism; high reward; high risk; hippocampal atrophy; informant; innovation; lifestyle data; lifestyle factors; mild cognitive impairment; modifiable lifestyle factors; neuroinflammation; physical conditioning; pre-clinical; prevent; prodromal Alzheimer' s disease; racial diversity; recruit; resilience; resilience factor; response; social engagement; sociodemographics; stem; tau Proteins; tau aggregation; tau-1; urban setting

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.

项目摘要 本行政补充材料是为了响应NOSI而提交的，用于资助项目，以满足NIH Down 综合征（DS）的研究目标与NIH的调查共发生的条件， 了解唐氏综合征的寿命（INCLUDE）项目（NOT-OD-20-024）。成年DS患者处于高风险状态 阿尔茨海默病（AD）的治疗方法。然而，在早期的发病年龄有明显的变化， 阿尔茨海默病病理学和DS临床痴呆的发病年龄父R 01的目标是 检查四种生活方式因素的影响-体力活动，睡眠，认知刺激和社交 参与-在患有AD的成人中进行AD、认知下降和临床AD状态的成像和生物流体生物标志物 DS.父R 01包括三个研究中心，并招募了140名DS成人，他们也在NIH注册- 阿尔茨海默氏病生物标志物联盟（ABC-DS; U19 AG 070043）。行政目标 补充是通过增加样本数量和增加样本社会性来加强母体R 01， 人口多样性。然后，将利用这一更大、更多样化的样本进行新的中介 分析以阐明DS中生活方式因素与AD之间的途径。该补充还针对 测试加速度计数据的先进分析方法，作为睡眠和身体健康的非侵入性生物标志物 活动在DS。为了实现这些目标，补充包括招募40名额外的成年人与DS进入 通过纳入一个新的研究中心（加州大学欧文分校）来取代母公司R 01。生活方式数据将收集在 这个新的群体在一个时间点。关于身体健康、睡眠、认知刺激和社交的信息 将使用自我/受访者报告和客观测量（活动记录仪和WatchPAT）收集参与度。 生活方式因素的数据收集将与AD生物标志物（PET）的ABC-DS数据收集及时对应 Aβ、PET tau、PET FDG、结构和功能MRI以及CSF Aβ和tau和血液）、认知功能， 和痴呆症的症状和状态。行政补助金的具体目标是：（1）增加 ABC-DS受试者的数量和社会人口统计学多样性（地理位置、种族和年龄） 入组父R 01; 2）测试生活方式因素影响的途径的中介模型 AD病理学、认知下降和DS中向MCI和AD痴呆转变的时间;和3） 比较处理和分析加速度计数据作为身体活动生物标志物的策略， 成年DS患者的睡眠中断。补充的信息将有助于确定生活方式是否是一种 重要的可改变的弹性机制，以延迟成人AD与DS。