Lifestyle and Alzheimer's Disease In Down Syndrome

生活方式与唐氏综合症中的阿尔茨海默病

• 批准号: 10696137
• 负责人: Sigan L Hartley
• 金额: $ 67.61万
• 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/10696137
• 关键词: Abeta synthesis; Address; Adult; Age; Age of Onset; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Attenuated; Automobile Driving; Biological Markers; Blood; Chromosome 21; Chronology; Clinical; Cognition; Cognitive; Data Collection; Dementia; Development; Down Syndrome; Early Onset Alzheimer Disease; Enrollment; Functional Magnetic Resonance Imaging; Funding; Genes; Genetic Risk; Impaired cognition; Investigation; Laos; Life Style; Longevity; Longitudinal Studies; Measures; Modeling; Nerve Degeneration; Pathway interactions; Phenotype; Physical activity; Plasma; Play; Population; Positron-Emission Tomography; Production; Psyche structure; Public Health; Reporting; Research; Research Design; Risk; Role; Science; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep Fragmentations; Symptoms; Time; United States National Institutes of Health; abeta accumulation; actigraphy; clinical risk; cognitive function; cohort; early experience; early onset; environmental agent; experience; indexing; interest; lifestyle factors; mild cognitive impairment; neuropathology; novel; physical conditioning; pre-clinical; prevent; protective factors; recruit; resilience; response; sedentary lifestyle; social engagement; tau Proteins; tau-1

Project Summary This application is being submitted in response to NIH's INCLUDE (OT-OD-20-025) Notice of Special Interest. The purposed R01 provides the first longitudinal investigation of the time-ordered effect of four lifestyle factors - physical activity, sleep, cognitive stimulation, and social engagement - on early Alzheimer's disease (AD) neuropathology and the transition to clinical AD in adults with Down syndrome (DS). These lifestyle factors will be assessed at a total of three time points, each spaced 16 months apart, in 140 adults with DS enrolled in the NIH-funded Alzheimer's Biomarker Consortium in DS (ABC-DS; https://www.nia.nih.gov/ research/abc-ds). Adults with DS are at genetic risk for AD due to the triplication of chromosome 21, which contains the gene for the amyloid precursor protein and thus results in an overproduction of amyloid-bet (Aβ). Despite this genetic risk, there is variability in the age of onset of clinical AD in the DS population. Lifestyle factors may contribute to this variability, as has been found in non-DS populations including adults with early-onset familial forms of AD. Indeed, as a group, adults with DS have been found to engage in a relatively high rate of sedentary behavior, experience a high rate of sleep problems, and to have lifestyles marked by low levels of cognitive stimulation and social engagement. In the proposed study, we will collect information on physical health, sleep, cognitive stimulation, and social engagement across a 7-day/night period at three time points (spaced 16 months apart). Self/information report and objective measures (actigraph and WatchPAT) are used to assess these lifestyle factors. This data collection will correspond in time with ABC-DS data collection of AD biomarkers, cognitive functioning, and dementia symptoms and status. Time-ordered associations between lifestyle factors and AD biomarkers (PET Aβ, PET tau, PET FDG, structural and functional MRI, and CSF Aβ and tau, and blood) and cognitive functioning and dementia will be examined. The specific aims of the study are to: 1) Examine the association between lifestyle factors –physical activity, sleep, cognitive stimulation, and social engagement – and AD biomarkers longitudinally (T1 to T3; each spaced 16-months apart); 2) Determine the association between lifestyle factors and cognitive functioning and dementia symptoms and status longitudinally (T1 to T3); 3) Evaluate the moderating role of lifestyle factors on the relation between early AD neuropathology (indexed by biomarkers) and cognitive functioning and dementia symptoms and status longitudinally (T1 to T3). These lifestyle factors may be important modifiable resiliency mechanisms for delaying clinical AD in adults with DS despite their genetic risk.

项目摘要 该申请是针对NIH提交的，包括（OT-OD-20-025）特别关注通知。 目的R01提供了对四个生活方式因素的定期效应的首次纵向研究 - 体育锻炼，睡眠，认知刺激和社会参与 - 早期阿尔茨海默氏病（AD） 唐氏综合症成年人（DS）的神经病理学和向临床AD的过渡。这些生活方式因素将 在总共三个时间点进行评估，每个时间点间隔16个月，在140名成年人中注册了DS NIH资助的阿尔茨海默氏症的生物标志物联盟（ABC-DS; https：//www.nia.nih.gov/ research/abc-ds）。 DS的成年人由于21染色体的三倍而面临AD的遗传风险，其中包含用于的基因 淀粉样蛋白前体蛋白，因此导致淀粉样蛋白-bet（Aβ）的生产过多。尽管有这种遗传 风险，DS人群的临床AD发作时代存在差异。生活方式因素可能会导致 对于这种变异性，正如非DS人群中发现的，包括具有早发性家庭形式的成年人 广告。确实，作为一个小组，已经发现患有DS的成年人从事久坐的相对高率 行为，经历高度的睡眠问题，并拥有以低水平的认知标志的生活方式 刺激和社会参与。在拟议的研究中，我们将收集有关身体健康，睡眠， 认知刺激和在三个时间点的7天/夜间进行社交参与度（间隔16 相隔几个月）。自我/信息报告和客观测量（Actigraph和WatchPat）用于评估 这些生活方式因素。此数据收集将与ABC-DS数据集合及时对应 生物标志物，认知功能以及痴呆症症状和状态。之间的时间订购的关联 生活方式因素和AD生物标志物（PETAβ，PET TAU，PET FDG，结构和功能性MRI以及CSFAβ 将检查和tau，血液）以及认知功能和痴呆症。研究的具体目的 为：1）检查生活方式因素之间的关联 - 身体活动，睡眠，认知刺激和 社会参与 - 纵向生物标志物（T1至T3；每个间隔16个月）； 2）确定 生活方式因素与认知功能与痴呆症状和状态之间的关联 纵向（T1至T3）； 3）评估生活方式因素在早期AD之间关系中的调节作用 神经病理学（由生物标志物索引）以及认知功能和痴呆症状和状态 纵向（T1至T3）。这些生活方式因素可能是重要的可修改弹性机制 在具有DS任务的成年人中延迟其遗传风险的临床广告。