Changes in Functioning among Mentally Retarded Adults

该计划项目自1987年以来一直支持一项多学科研究计划，重点是智力落后的成年人口中老龄化和痴呆症的各个方面。唐氏综合征(DS)成年人的老龄化受到特别关注，因为他们的预期寿命减少，患阿尔茨海默病(AD)的风险显著增加。基于我们以前工作提供的基础，我们现在寻求扩展我们的研究计划，通过关注患有DS的个人来解决几个重要的问题。我们的 方案项目将包括由两个核心支持的五个子项目，主要调查领域将集中在：(A)影响DS人群中AD个人风险的因素，(B)随着痴呆症的发展以及认知和功能进步的下降而出现适应不良行为，(C)发展可用于有效分类/诊断痴呆症的功能和认知能力的客观测量 (D)对DS患者一生中运动系统病理的形态计量研究，以及(E)寿命发育和AD相关病理对DS患者特定脑结构内基因表达的影响。我们的整体计划一直包括平衡的工作组合。我们的一些研究旨在描述我们目标人群中的衰老和痴呆症，而另一些研究则专注于在AD的风险和进展中发挥关键作用的基本生物学过程。在接下来的时间 五年后，我们计划将这种平衡转移到对AD的诊断、治疗和预防有更直接影响的问题上，无论是对患有DS的成年人还是更广泛的AD。 与过去一样，我们的活动将通过代表不同学科的大型调查团队之间的互动而得到加强，这些学科包括流行病学、遗传学、免疫学、分子生物学、神经学、神经病理学、精神病学、心理学和统计学。正是这种多学科的环境使我们能够进行我们过去产生的研究，而我们现在提议的工作将非常困难，也许在任何其他情况下都不可能完成。

This Program Project has supported a multidisciplinary program of research since 1987, focused on various aspects of aging and dementia in the adult population with mental retardation. The aging of adults with Down syndrome (DS) has received special attention due to their reduced life expectancy and dramatically increased risk of Alzheimer' disease (AD). Based upon the foundation provided by our previous work, we now seek to extend our program of research to address several issues of major significance by focusing on individuals with DS. Our Program Project will include five Subprojects supported by two Cores, and major areas of investigation will focus on: (a) factors that influence individual risk for AD within the DS population, (b) the emergence of maladaptive behaviors as dementia develops and as declines in cognition and function progress, (c) development of objective measures of functional and cognitive abilities that can be used for valid classification/diagnosis of dementia in the population with DS, (d) morphometric studies of motor system pathology throughout the lifespan of individuals with DS, and (e) the influence of lifespan development and AD associated pathology on gene expression within specific brain structures of individuals with DS. Our overall program has always included a balanced mixture of work. Some of our studies were designed to describe aging and dementia within our target population, while other studies focused on basic biological processes playing key roles in risk for and progression of AD. Over the next five years, we plan to shift this balance toward issues that have more direct implications for diagnosis, treatment and prevention of AD, both for adults with DS and more broadly. As in the past, our activities will be enhanced by the interactions among a large team of investigators representing diverse disciplines, including epidemiology, genetics, immunology, molecular biology, neurology, neuropathology, psychiatry, psychology and statistics. It is this multidisciplinary environment that has enabled us to conduct the research we have generated in the past, and the work we are now proposing would be exceedingly difficult, perhaps impossible to do in any other context.