Lifestyle and Alzheimer’s Disease In Down Syndrome- Life Stressors Supplement

项目摘要 唐氏综合征（DS）患者的证据表明，由于有三个β淀粉样蛋白（Aβ）， 21号染色体的拷贝。随着年龄的增长，Aβ聚集成细胞外脑斑块，这是一个标志， 阿尔茨海默病（AD）的一个特征;然而，这种AD病理开始的年龄存在变异性 以及临床AD病理学如何在DS中展开。压力的生活经历，无论是在童年和 与年龄相关的认知能力下降和DS以外的散发性迟发性AD风险相关。 应激性生活经历可能会加剧AD病理和/或其通过炎症对认知的影响， 和/或通过促成条件（例如，肥胖症、心血管疾病、抑郁症、睡眠障碍）， 已知的AD风险因素。 行政补充的目标，“生活压力和阿尔茨海默氏病的唐氏综合征，”是 扩展R 01 AG 70028“生活方式风险和恢复力因素与阿尔茨海默病在下 综合征”项目，以检查不良儿童事件的影响（例如，父母离婚，虐待/忽视， 贫困）和最近的生活压力（例如，工作终止、新员工、家庭成员死亡）对AD时间的影响 唐氏综合症患者的病理学和病理学。具体而言，该补充将：1）包括 生活方式R 01方案中的新措施，以捕获不良儿童经历（ACE）; 2）使用新的 编码技术，以捕捉成年期的压力生活事件; 3）进行新的分析，以确定 压力性童年和成年生活经历与AD成像和生物流体生物标志物之间的关联 和认知障碍。 父母R 01跟随180名患有DS的成年人，他们共同参加了NIH资助的阿尔茨海默氏症生物标志物 DS联合会（ABC-DS），其中AD生物标志物（例如，PET Aβ和tau、CSF Aβ42和血浆p-tau 217）、认知功能和痴呆状态。父生活方式R 01收集三次 数据点，与ABC-DS周期一致，并侧重于四个可改变的生活方式因素-身体活动， 睡眠、认知刺激和社会参与。生活压力与阿尔茨海默病 综合征”行政补编将在这些目标的基础上， 生活压力对DS中AD的影响，可以推动未来的社会政策和干预措施。

PROJECT SUMMARY People with Down syndrome (DS) evidence an overproduction of amyloid-beta (Aβ), due to having three copies of chromosome 21. With age, Aβ aggregates into extracellular brain plaques, which is a hallmark feature of Alzheimer’s disease (AD); however, there is variability in the age at which this AD pathology begins and how clinical AD symptomology unfolds in DS. Stressful life experiences, both in childhood and in adulthood, are associated with aging-related cognitive decline and risk of sporadic late onset AD outside of DS. Stressful life experiences may exacerbate AD pathology and/or its effects on cognition through inflammation, and/or by contributing to conditions (e.g., obesity, cardiovascular disease, depression, sleep disorders) that are known risk factors for AD. The goal of the Administrative Supplement, “Life Stressors and Alzheimer’s Disease in Down syndrome,” is to expand on the R01AG70028 “Lifestyle Risk and Resiliency Factors and Alzheimer’s Disease in Down syndrome” project to examine the effect of adverse childhood events (e.g., parent divorce, abuse/neglect, poverty) and recent life stressors (e.g., job termination, new staff, death of family member) on the timing of AD pathology and symptomology in people with Down syndrome. Specifically, this supplement will: 1) include a new measure into the Lifestyle R01 protocol to capture adverse childhood experiences (ACEs); 2) use a new coding technique to capture stressful life events in adulthood; and 3) conduct new analyses to determine the association between stressful childhood and adult life experiences and AD imaging and biofluid biomarkers and cognitive impairments. The parent R01 follows 180 adults with DS who are co-enrolled in the NIH-funded Alzheimer’s Biomarker Consortium in DS (ABC-DS), in which AD biomarkers (e.g., PET Aβ, and tau, CSF Aβ42, and plasma p-tau 217), cognitive functioning, and dementia status are collected. The parent Lifestyle R01 collects three time points of data, aligning with ABC-DS cycles, and focuses on four modifiable lifestyle factors – physical activity, sleep, cognitive stimulation, and social engagement. The “Life Stressors and Alzheimer’s Disease in Down syndrome” Administrative Supplement will build on these aims by generating novel and significant information on the effect of life stressors on AD in DS that can drive social policy and interventions in the future.