Early Cognitive Decline in Down Syndrome

摘要 唐氏综合症（DS）是由21号染色体的额外拷贝引起的，这导致了各种各样的 结果包括独特的面部特征，医疗脆弱性和智力残疾。其还导致 过早衰老过程和阿尔茨海默氏痴呆症（AD）的高风险，两者都与认知功能相关。 下降DS研究的一个重要目标是了解认知衰退的发展过程， 包括各种认知功能的衰退何时（或在什么年龄）开始开始。这些知识将开启 早期药物，行为或环境干预的大门，旨在减缓疾病的进展 老年痴呆症和AD拟议项目的广泛、长期目标是尽早确定 青少年晚期至成年早期DS患者的认知能力下降。拟议的三年 纵向研究将招募年龄在15-25岁之间的DS受试者。这个年龄段正好在 在健康的神经典型成年人中，认知能力下降在某些功能上变得明显。此外，淀粉样蛋白 有证据表明，这一年龄段可能与DS中AD的临床前阶段非常一致 人口参与者将完成一系列认知和行为测量，间隔三次，每次18- 每隔一个月，为期三年。这些指标（a）与老年人中的AD进展有关 患有DS的成年人（例如，Krinsky-McHale，Devenny，& Silverman，2002）或（B）最近被记录为 在这个年龄段下降（Conners，Tungate，Abbeduto，梅里尔，& Faught，2018）。证候特异性 将通过比较DS受试者与匹配的非DS智力残疾受试者进行评估 年龄和非语言能力。此外，还将测量各种协变量，以进一步增强对 发展趋势。目的1是识别早期认知衰退（情景记忆，执行功能， 语音记忆，表达性词汇，接受性语法）;目的2是确定其他变化 与衰老和/或向AD进展相关的结构域（例如，适应不良行为 行为、步态和心理速度）;目标3是将观察到的认知和行为变化与 MCI的症状（例如，日常定向、注意力集中、基本功能） 如改良的简易精神状态检查。拟议的研究将通过确定 发展趋势（特别是下降）在一个独特的年龄范围内的DS在广泛的措施。 未来的发展方向包括延长纵向时间框架，增加淀粉样蛋白/tau蛋白指标，以更好地 将下降解释为与AD相关或无关。

ABSTRACT Down syndrome (DS) is caused by an extra copy of chromosome 21, which results in a wide variety of outcomes including unique facial features, medical vulnerabilities, and intellectual disability. It also results in premature aging processes and a high risk for Alzheimer's dementia (AD), both associated with cognitive decline. One crucial goal of research on DS is to understand the developmental course of cognitive decline, including when (or at what age) declines in various cognitive functions begin. This knowledge would open the door to early pharmaceutical, behavioral, or environmental interventions designed to slow the progression of early aging and AD in this population. The broad, long-term objective of the proposed project is to identify early cognitive decline in youth with DS during late adolescence into early adulthood. The proposed 3-year longitudinal study will enroll participants with DS aged 15-25 years. This age period is just before the age when cognitive decline becomes apparent in some functions in healthy neurotypical adults. Further, amyloid evidence suggests that this age period may very well align with the preclinical stage of AD in the DS population. Participants will complete a battery of cognitive and behavioral measures three times spaced at 18- month intervals, for a span of three years. The measures either (a) have been linked to AD progression in older adults with DS (e.g., Krinsky-McHale, Devenny, & Silverman, 2002) or (b) have been documented recently as declining during this age period (Conners, Tungate, Abbeduto, Merrill, & Faught, 2018). Syndrome specificity will be assessed by comparing participants with DS to participants with non-DS intellectual disability matched on age and nonverbal ability. Also, a variety of covariates will be measured to further enhance interpretation of developmental trends. Aim 1 is to identify early cognitive decline (episodic memory, executive function, phonological memory, expressive vocabulary, receptive grammar); Aim 2 is to identify changes in other domains that are related to aging and/or progression toward AD (e.g., adaptive behavior, maladaptive behavior, gait, and psychomotor speed); Aim 3 is to link observed cognitive and behavioral changes to symptoms of MCI (e.g., everyday orientation, concentration, basic functioning) as measured by instruments such as the Modified Mini-Mental State Exam. The proposed study will move the field forward by identifying developmental trends (especially declines) in a unique age range in DS across a broad array of measures. Future directions include extending the longitudinal time frame and adding amyloid/tau measures to better interpret declines as AD-related or not.