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、医疗漏洞和智力残疾。它还会导致 过早衰老过程和阿尔茨海默氏病(AD)的高风险，两者都与认知相关 拒绝。DS研究的一个重要目标是了解认知衰退的发展过程， 包括各种认知功能开始衰退的时间(或年龄)。这一知识将打开 早期药物、行为或环境干预的大门，旨在减缓疾病的进展 这一人群中的早期老龄化和阿尔茨海默病。拟议项目的广泛、长期目标是及早确定 青少年DS患者在青春期晚期至成年期早期的认知衰退。建议的3年期 纵向研究将招募年龄在15-25岁的DS患者。这一年龄段恰好是在 在健康的神经典型成年人中，认知能力下降在一些功能上变得明显。此外，淀粉样蛋白 有证据表明，这一年龄段可能与DS的AD临床前阶段非常一致。 人口。参与者将在18岁时完成一系列认知和行为测量，每隔三次- 每隔一个月，跨度为三年。这些措施或(A)与老年AD的进展有关 患有DS(例如，Krinsky-McHale，Devenny和Silverman，2002)或(B)的成年人最近被记录为 在这个年龄段(Conners，Tungate，Abbeduto，Merrill，&Fauight，2018)。证候特异性 将通过比较患有DS的参与者和匹配的非DS智力残疾的参与者来进行评估 年龄和非语言能力。此外，还将测量各种协变量，以进一步加强对 发展趋势。目标1是识别早期认知衰退(情节记忆、执行功能、 语音记忆、表达词汇、接受性语法)；目标2是识别其他 与衰老和/或向AD进展有关的领域(例如，适应行为、适应不良 行为、步态和精神运动速度)；目标3是将观察到的认知和行为变化与 通过仪器测量的MCI症状(例如，日常定向、注意力集中、基本功能) 例如修改后的迷你精神状态检查。拟议的研究将通过以下方式推动该领域的发展： 在一系列广泛的测量中，DS在独特的年龄范围内的发展趋势(特别是下降)。 未来的方向包括延长纵向时间框架和增加淀粉样蛋白/tau措施以更好地 将下降解释为与AD有关或无关。

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.