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: 10098587
• 负责人: Sigan L Hartley
• 金额: $ 79.44万
• 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/10098587
• 关键词: 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; Enrollment; Functional Magnetic Resonance Imaging; Funding; Genes; Genetic Risk; Impaired cognition; Investigation; Laos; Lead; Life Style; Longevity; Longitudinal Studies; Measures; Modeling; Nerve Degeneration; Pathway interactions; Phenotype; Physical activity; Plasma; Play; Population; Positron-Emission Tomography; Presenile Alzheimer Dementia; Production; Psyche structure; Public Health; Reporting; Research; Research Design; Risk; Role; Science; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep Fragmentations; Structure; 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.

项目概要 本申请是为了响应 NIH 的 INCLUDE (OT-OD-20-025) 特别兴趣通知而提交的。 R01 首次对四种生活方式因素的时间顺序影响进行纵向调查 - 体力活动、睡眠、认知刺激和社交参与 - 关于早期阿尔茨海默病 (AD) 唐氏综合症 (DS) 成人的神经病理学和向临床 AD 的转变将取决于这些生活方式因素。 在总共三个时间点对 140 名 DS 成人进行评估，每个时间点间隔 16 个月。 NIH 资助的 DS 阿尔茨海默病生物标志物联盟 (ABC-DS；https://www.nia.nih.gov/research/abc-ds)。 患有 DS 的成年人由于 21 号染色体的三倍体而面临 AD 的遗传风险，该染色体含有 淀粉样蛋白前体蛋白，因此导致淀粉样蛋白 (Aβ) 的过量产生，尽管有这种遗传。 DS 人群中临床 AD 的发病年龄存在差异，生活方式因素可能有所影响。 这种变异性，正如在非 DS 人群（包括患有早发家族性 DS 的成年人）中所发现的那样 事实上，作为一个群体，患有 DS 的成年人久坐的比例相对较高。 行为、睡眠问题发生率较高以及认知水平较低的生活方式 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 7 天/夜期间三个时间点（间隔 16 自我/信息报告和客观测量（actigraph 和 WatchPAT）用于评估。 这些生活方式因素的数据收集将与 AD 的 ABC-DS 数据收集及时对应。 生物标志物、认知功能以及痴呆症状和状态之间的时间顺序关联。 生活方式因素和 AD 生物标志物（PET Aβ、PET tau、PET FDG、结构和功能 MRI 以及 CSF Aβ 并将检查认知功能和痴呆症。 目的是： 1) 检查生活方式因素之间的关联——体力活动、睡眠、认知刺激和 社会参与——纵向和 AD 生物标志物（T1 到 T3；每个间隔 16 个月）；2) 确定 生活方式因素与认知功能以及痴呆症症状和状态之间的关联 纵向（T1至T3）；3）评估生活方式因素对早期AD之间关系的调节作用 神经病理学（由生物标志物索引）和认知功能以及痴呆症状和状态 纵向（T1 到 T3），这些生活方式因素可能是重要的可改变的弹性机制。 尽管存在遗传风险，但仍可延迟患有 DS 的成人的临床 AD。