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

项目总结 唐氏综合征(DS)患者有证据表明淀粉样β蛋白(Aβ)产生过多，原因是有三个 21号染色体的副本。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)的特征；然而，这种AD病理开始的年龄是不同的 以及阿尔茨海默病的临床症状如何在DS中展开。有压力的生活经历，无论是在童年还是在 成年期，与衰老相关的认知能力下降和散发性迟发性AD的风险有关。 紧张的生活经历可能会加剧AD的病理和/或其通过炎症对认知的影响， 和/或通过促进以下情况(例如，肥胖、心血管疾病、抑郁症、睡眠障碍) 阿尔茨海默病的已知风险因素。 行政副刊《唐氏综合症中的生活应激源和阿尔茨海默病》的目标是 R01AG70028“生活方式风险和复原力因素与唐氏阿尔茨海默病 研究儿童时期不良事件(如父母离婚、虐待/忽视、 贫困)和最近的生活压力因素(例如，工作终止、新员工、家庭成员死亡)与AD的发生时间有关 唐氏综合征患者的病理学和症状学。具体地说，本补编将：1)包括 生活方式R01协议的新措施，以捕获不良童年经历(ACE)；2)使用新的 编码技术，以捕捉成年后的压力生活事件；以及3)进行新的分析，以确定 儿童和成人生活经历与AD影像和生物体液生物标志物的关系 和认知障碍。 父母R01跟踪了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记物 DS联盟(ABC-DS)，其中AD生物标志物(例如，PET Aβ和tau、CSFAβ42和血浆p-tau 217)，认知功能和痴呆症状态被收集。家长生活方式R01集三次 数据点，与ABC-DS周期一致，并专注于四个可改变的生活方式因素-体力活动， 睡眠、认知刺激和社交活动。《唐人街生活压力源与阿尔茨海默病》 《综合症》行政副刊将以这些目标为基础，通过产生新的和重要的信息来实现 关于生活压力源对DS患者AD的影响，以推动未来的社会政策和干预。

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.