Aging and Dementia in Adults with Down Syndrome

自1987年以来一直在进行的以唐氏综合症（DS）成人为重点的研究计划将继续下去，现在由三个核心支持的四个项目组成。 虽然所有的项目都有明确的起源，在该方案的当前活动，几个新的举措包括在内。 研究者将：（a）确定患有DS的老年人群中阿尔茨海默病（AD）风险的个体差异是否与胰岛素抵抗和代谢综合征的其他特征相关;（B）开发经验验证的方法，用于鉴定患有DS的成年人中轻度认知损害（MCI）的存在，将这种状况与与发育适当的衰老本身相关的认知变化区分开;（c）确定改变的DNA甲基化模式在DS发病机制中的作用和该群体中表型表达的变化，包括选定的衰老相关过程;和（d）使用独立的数据集来评估AD发作时年龄之间的关系，（以及相关的表型特征）和单核苷酸多态性（SNP）位于21号染色体和其他染色体上的大约60个候选基因。 与过去一样，将通过代表多个学科的调查人员之间的广泛合作来实现目标。 共同的评估程序，重复间隔约18个月，将被用来详细描述健康，认知和功能状态的300名成年人与DS积极参与该计划。 以前研究的结果和生物样本也将用于现在提出的遗传和表观遗传研究，使预计的总样本量达到788名成年DS患者。 认知和功能变化将与选定的生物标志物以及遗传和表观遗传学发现相关，这为该人群提供了比任何单一研究项目更丰富的描述。 研究结果应提供清晰的见解：（a）机制的DS表型的重要特征，（B）这些功能的个体差异，（c）因素修改痴呆的风险，（d）评估方法，可以告知诊断决策相对早期的疾病进展。 此外，一些研究结果可能对促进DS成人更成功的衰老有直接影响。

The program of research focusing on adults with Down syndrome (DS), ongoing since 1987, will be continued, now consisting of four projects supported by three cores. While all of the projects have clear origins in the program's current activities, several new initiatives are included. The investigators will: (a) determine if individual differences in risk for Alzheimer's disease (AD) within the elderly population with DS is associated with insulin resistance and other features of metabolic syndrome; (b) develop empirically validated methods for identifying the presence of mild cognitive impairment (MCI) in adults with DS, differentiating this condition from cognitive changes associated with developmentally appropriate aging, per se; (c) determine the role of altered patterns of DNA methylation in DS pathogenesis and variation in phenotypic expression within this population, including selected aging-related processes; and (d) use independent datasets to evaluate the relations between age at onset of AD (as well as related phenotypic characteristics) and single nucleotide polymorphisms (SNPs) of approximately 60 candidate genes located on chromosome 21 as well as other chromosomes. As in the past, goals will be achieved through extensive collaborations among investigators representing multiple disciplines. Common assessment procedures, repeated at intervals of approximately 18 months, will be employed to characterize in detail the health, cognitive, and functional status of each of the 300 adults with DS actively participating in the program. Findings and biological samples from previous studies will also be available for the genetic and epigenetic studies now being proposed, bringing the total projected sample size to 788 adults with DS. Cognitive and functional changes will be related to selected biomarkers as well as genetic and epigenetic findings, providing a far richer description of this population than could occur in the context of any single research project. Findings should provide clear insights into: (a) mechanisms underlying important features of the DS phenotype, (b) individual differences in those features, (c) factors modifying risk for dementia, and (d) assessment methods that can inform diagnostic decisions relatively early in disease progression. Further, some findings may have direct implications for promoting more successful aging for adults with DS.