Aging and Dementia in Adults with Down Syndrome

自1987年以来一直在进行的以成人唐氏综合症(DS)为重点的研究计划将继续进行，目前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于该计划目前的活动，但也包括了几个新的倡议。研究人员将：(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其他代谢综合征特征有关；(B)开发经经验验证的方法来识别患有DS的成年人中是否存在轻度认知障碍(MCI)，将这种情况与与发育适宜的衰老相关的认知变化区分开来；(C)确定DNA甲基化改变在DS发病机制和该人群中表型表达变化中的作用，包括选定的与衰老相关的过程；以及(D)使用独立的数据集来评估AD发病年龄(以及相关的表型特征)与位于21号染色体和其他染色体上的大约60个候选基因的单核苷酸多态(SNPs)之间的关系。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。每隔大约18个月重复一次的通用评估程序将被用来详细描述积极参与该计划的300名患有DS的成年人的健康、认知和功能状况。先前研究的结果和生物样本也将用于目前正在提议的遗传和表观遗传学研究，使预计的总样本量达到788名患有DS的成年人。认知和功能变化将与选定的生物标记物以及遗传和表观遗传学发现有关，比任何单一研究项目提供的对这一群体的描述要丰富得多。研究结果应该为以下方面提供明确的见解：(A)DS表型重要特征的潜在机制，(B)这些特征的个体差异，(C)改变痴呆风险的因素，以及(D)可在疾病进展中相对早期做出诊断决定的评估方法。此外，一些发现可能对促进患有DS的成年人更成功地衰老具有直接意义。

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.