Predictors of mortality and of healthy survival in a large community-based prospective cohort of aging adults with Down syndrome

项目摘要 患有唐氏综合症的成年人比以往任何时候都活得更长，但他们的预期寿命仍然短于 普通民众。最常见的死亡原因是呼吸衰竭、痴呆和 心血管疾病尽管最常见的死亡原因已经确定，但可以改变 死亡率的预测因素仍然未知。此外，对心血管风险因素进行更具包容性的评估 他们对死亡率的特定预测价值将帮助我们更好地了解他们的心血管风险状况。 最后，定义一组“健康的幸存者”使我们能够采取“积极的生物学”方法， 预测衰老的因素，而不包括这一人群正在经历的许多疾病。更好地了解 不可改变和可改变的风险因素（如健康行为）对于进一步降低早期死亡率至关重要 通过制定与生活方式有关的预防方案、早期发现、筛查和诊断战略， 充分分配医疗资源。 我们建议利用我们的经验和专业知识， 纵向队列研究健康老龄化和智力残疾（HA-ID）， 了解唐氏综合征老年人死亡率和“健康幸存者”的预测因素。医管局─ ID数据集包括n=1050名年龄≥50岁的智力残疾（ID）老年人，包括n=149名成人 患有唐氏综合症HA-ID数据集主要包括一组广泛的基线健康结果 通过临床和亲自评估收集，包括可改变的风险因素，如健康行为。 此外，在基线后3年和5年纵向收集发病率和死亡率， 目前正在完成一年的后续数据收集工作。我们的长期目标是改善健康老龄化， 通过确定可改变的风险因素作为生活方式相关预防的目标， 战略和早期发现和诊断战略。因此，本研究的拟议目标是： 目的1：描述社区老年唐氏症患者的死亡原因和存活率 综合征，并与无唐氏综合征的ID老年人的匹配样本进行对比。 目标2：确定死亡率的可修改和不可修改的预测因素（包括一个全面的心血管 风险特征）在HA-ID研究中，以社区为基础的唐氏综合征老年人样本中。 目的3：确定唐氏综合征老年人中“健康幸存者”的特征。 该项目将确定生活方式相关策略的目标，以支持成年唐氏症患者的健康老龄化 综合征和早期检测和诊断策略。这些见解将为分配提供方向 卫生保健资源，告知纵向研究的关键健康措施，以考虑，并激励 老年唐氏综合征健康实验研究的机制问题。这些 结果符合NIH纳入2021年唐氏综合症研究计划中所述的雄心。

Project Summary Adults with Down syndrome live longer than ever before, however their life expectancy is still shorter than in the general population. The most common causes of death are respiratory failure, dementia and cardiovascular disease. Although the most prevalent causes of mortality have been identified, modifiable predictors of mortality are still unknown. Additionally, a more inclusive evaluation of cardiovascular risk factors and their specific predictive value for mortality will help us better understand their cardiovascular risk profile. Lastly, defining a group of “healthy survivors” allows us to take a ‘positive biology’ approach and determine the predictors for aging without many of the diseases this population is experiencing. A better understanding of non-modifiable and modifiable risk factors (such as health behaviors) is critical to further combat early mortality by developing lifestyle-related prevention programs, early detection, screening and diagnosing strategies, and adequate allocation of health care resources. We propose to leverage our experience and expertise with the population-based, prospective, longitudinal cohort study Healthy Aging and Intellectual Disability (HA-ID) to uniquely contribute to the understanding of predictors for mortality and “healthy survivors” in aging adults with Down syndrome. The HA- ID dataset includes n=1050 aging adults with intellectual disabilities (ID) of ≥50 years including n=149 adults with Down syndrome. The HA-ID dataset includes an extensive set of baseline health outcomes mostly collected through clinical and in-person evaluation, including modifiable risk factors such as health behaviors. Additionally, morbidity and mortality have been collected longitudinally 3 and 5 years after baseline, and the 10 year follow up data collection is currently being completed. Our long-term goal is to improve healthy aging for adults with Down syndrome by identifying modifiable risk factors as targets for lifestyle-related prevention strategies and early detection and diagnosis strategies. Therefore, the proposed aims of this study are: Aim 1: Describe causes of mortality and survival rates in a community-based sample of aging adults with Down syndrome and contrast with a matched sample of aging adults with ID without Down syndrome. Aim 2: Identify modifiable and non-modifiable predictors of mortality (including a comprehensive cardiovascular risk profile) in a community-based sample of aging adults with Down syndrome in the HA-ID study. Aim 3: Identify the characteristics of ‘healthy survivors’ in aging adults with Down syndrome. This project will identify targets for lifestyle-related strategies to support healthy aging in adults with Down syndrome and for early detection and diagnosis strategies. These insights will provide directions for allocation of health care resources, inform longitudinal studies on critical health measures to consider, and inspire mechanistic questions for experimental studies on health in aging adults with Down syndrome. These outcomes are in line with the ambitions stated in the NIH INCLUDE Down Syndrome Research Plan 2021.