Lifestyle and Alzheimer's Disease In Down Syndrome

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) 神经病理学和成人唐氏综合症 (DS) 向临床 AD 的转变。这些生活方式因素会 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，从而导致淀粉样蛋白 (Aβ) 过量产生。尽管有这种遗传 风险，DS 人群中临床 AD 的发病年龄存在差异。生活方式因素可能会造成影响 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 公元。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 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 7 天/夜期间三个时间点（间隔 16 相隔几个月）。使用自我/信息报告和客观测量（actigraph 和 WatchPAT）来评估 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 以及 tau 蛋白和血液）以及认知功能和痴呆症将得到检查。研究的具体目的 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 至 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。

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.