Lifestyle and Alzheimer's Disease In Down Syndrome

项目摘要 本申请是根据NIH的INCLUDE（OT-OD-20-025）特别关注通知提交的。 目的R 01提供了四种生活方式因素的时间顺序效应的第一次纵向调查 - 身体活动，睡眠，认知刺激和社会参与-早期阿尔茨海默病（AD） 神经病理学和唐氏综合征（DS）成人向临床AD的转变。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DS患者中， NIH资助的阿尔茨海默氏症生物标志物联盟（ABC-DS; https://www.nia.nih.gov/ research/abc-ds）。 患有DS的成年人由于21号染色体的三倍而具有AD的遗传风险，该染色体含有 淀粉样前体蛋白，从而导致淀粉样蛋白-bet（Aβ）的过度产生。尽管这种基因 风险，DS人群中临床AD的发病年龄存在变异性。生活方式因素可能会导致 这种变异性，如在非DS人群中发现的，包括早发性家族性形式的成人， AD.事实上，作为一个群体，患有DS的成年人被发现从事相对较高的久坐不动 行为，经历高比率的睡眠问题，并有低认知水平的生活方式 激励和社会参与。在拟议的研究中，我们将收集有关身体健康，睡眠， 认知刺激和社会参与在三个时间点（间隔16 相隔数月）。自我/信息报告和客观测量（活动记录仪和WatchPAT）用于评估 这些生活方式因素。该数据收集将与AD的ABC-DS数据收集在时间上一致 生物标志物、认知功能和痴呆症状和状态。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 和tau，和血液）和认知功能和痴呆症将被检查。研究的具体目标 1）检查生活方式因素之间的关联-体力活动，睡眠，认知刺激， 社会参与-和AD生物标志物纵向（T1至T3;每个间隔16个月）; 2）确定 生活方式因素与认知功能和痴呆症状和状态之间的关联 纵向（T1至T3）; 3）评估生活方式因素对早期AD与 神经病理学（通过生物标志物索引）和认知功能以及痴呆症状和状态 纵向（T1至T3）。这些生活方式因素可能是重要的可改变的弹性机制， 延缓DS成人的临床AD，尽管他们有遗传风险。

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.