Lifestyle and Alzheimer's Disease In Down Syndrome

项目摘要 本申请是根据美国国立卫生研究院的INCLUDE(OT-OD-20-025)特殊利益通知提交的。 R01首次对四种生活方式因素的时序效应进行了纵向研究 -身体活动、睡眠、认知刺激和社交--关于早期阿尔茨海默病(AD) 唐氏综合征(DS)成人患者的神经病理学和向临床AD的转变。这些生活方式因素将 在140名患有DS的成年人中，总共在三个时间点进行评估，每个时间点相隔16个月 美国国立卫生研究院资助的阿尔茨海默氏症生物标记物DS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患AD的遗传风险，21号染色体包含 淀粉样前体蛋白，从而导致淀粉样蛋白(Aβ)的过度生产。尽管有这样的基因 风险，在DS人群中，临床AD的发病年龄存在差异。生活方式因素可能起到一定作用 对于这种变异性，在非DS人群中发现，包括具有早发性家族形式的成人 广告。事实上，作为一个群体，人们发现患有DS的成年人久坐的比例相对较高 行为，经历高比例的睡眠问题，生活方式以低水平的认知为标志 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，以及在三个时间点的7个昼夜期间的社交参与(间隔16 相隔数月)。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、痴呆症症状和状态。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、结构和功能磁共振以及脑脊液Aβ 和tau，以及血液)以及认知功能和痴呆症。这项研究的具体目的 是为了：1)检查生活方式因素--体育活动、睡眠、认知刺激和 社会参与度-和AD生物标记物纵向(T1至T3；每个间隔16个月)；2)确定 生活方式因素与认知功能及痴呆症状和状态的关系 纵向(T1至T3)；3)评价生活方式因素对早期AD关系的调节作用 神经病理学(以生物标记物为指标)和认知功能及痴呆症状和状态 纵向(T1至T3)。这些生活方式因素可能是重要的可修改的弹性机制 推迟成年DS患者的临床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.