Aging and Dementia in Adults with Down Syndrome

以成人唐氏综合症（DS）为重点的研究项目自1987年以来一直在进行，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，在计划的当前活动，一些新的倡议包括在内。研究人员将：(a)确定老年退行性痴呆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，用于识别成人退行性痴呆患者是否存在轻度认知障碍（MCI），将这种情况与与发育适宜性衰老本身相关的认知变化区分开来；(c)确定DNA甲基化模式改变在该人群中DS发病机制和表型表达变异中的作用，包括选定的衰老相关过程；(d)使用独立数据集评估阿尔茨海默病发病年龄（以及相关表型特征）与21号染色体及其他染色体上约60个候选基因的单核苷酸多态性（snp）之间的关系。与过去一样，目标将通过代表多个学科的研究人员之间的广泛合作来实现。每隔大约18个月重复一次的普通评估程序，将用于详细描述300名积极参与该计划的退行性痴呆成年人的健康、认知和功能状态。先前研究的结果和生物样本也将用于目前正在提出的遗传和表观遗传学研究，使预计的总样本量达到788名成年退行性痴呆患者。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发现有关，这将提供比任何单一研究项目更丰富的种群描述。研究结果应该为以下方面提供清晰的见解：(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)可以在疾病进展相对早期告知诊断决策的评估方法。此外，一些研究结果可能对促进退行性椎体滑移成人更成功的衰老具有直接意义。

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.