Early Cognitive Decline in Down Syndrome

唐氏综合症的早期认知能力下降

• 批准号: 10654596
• 负责人: FRANCES A CONNERS
• 金额: $ 64.26万
• 依托单位: UNIVERSITY OF ALABAMA IN TUSCALOOSA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10654596
• 关键词: 20 year old; Acceleration; Adaptive Behaviors; Address; Adolescence; Adolescent; Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid; Behavior Therapy; Behavioral; Biochemical; Brain; Chromosome 21; Clinical; Cognitive; Cognitive aging; Dementia; Detection; Development; Developmental Course; Diagnosis; Disease Management; Disease Progression; Down Syndrome; Early identification; Educational workshop; Elderly; Episodic memory; Etiology; Event; Face; Funding; Future; Gait; General Population; Goals; Head; Impaired cognition; Individual; Intellectual functioning disability; Investigation; Knowledge; Language; Life; Link; Longevity; Longitudinal Studies; Matched Group; Measures; Memory; Mental Depression; National Institute of Child Health and Human Development; Natural History; Outcome; Participant; Pathologic; Performance; Persons; Pharmacologic Substance; Population; Premature aging syndrome; Process; Quality of life; Reporting; Research; Research Project Grants; Signal Transduction; Sleep Disorders; Specificity; Speed; Symptoms; Syndrome; Thyroid Function Tests; Time; United States National Institutes of Health; Update; Vocabulary; Youth; aged; behavior measurement; cognitive change; cognitive function; cognitive testing; design; emerging adult; environmental intervention; executive function; healthy aging; high risk; improved; instrument; maladaptive behavior; medical vulnerability; mental state; mild cognitive impairment; neuropathology; non-verbal; participant enrollment; phonology; pre-clinical; progression marker; skills; tau Proteins; therapy design; trend; young adult

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.

抽象的 唐氏综合症（DS）是由21号染色体的额外副本引起的，这导致了多种多样 结果包括独特的面部特征，医疗漏洞和智力残疾。这也导致 早熟的过程和阿尔茨海默氏痴呆症（AD）的高风险与认知有关 衰退。 DS研究的一个关键目标是了解认知能力下降的发展过程， 包括何时开始（或在哪个年龄）开始各种认知功能。这些知识将打开 旨在减缓进展的早期药物，行为或环境干预措施 该人群的早期衰老和广告。拟议项目的广泛，长期目标是早期确定 青春期青年青年的认知能力下降到成年初。拟议的3年 纵向研究将招募15-25岁DS的参与者。这个年龄段就在年龄之前 在健康的神经型成年人中，某些功能的认知能力下降变得显而易见。此外，淀粉样蛋白 有证据表明，这个年龄时期很可能与DS中AD的临床前阶段保持一致 人口。参与者将完成一系列认知和行为措施，分别为18-- 每月间隔，持续三年。措施（a）与较老的AD进展有关 DS的成年人（例如Krinsky-Mchale，Devenny和Silverman，2002年）或（b）已被记录为 在这个年龄段的下降（Conners，Tungate，Abbeduto，Merrill和Faught，2018年）。综合征特异性 将通过将DS参与者与非DS智力残疾的参与者进行比较来评估 年龄和非语言能力。此外，将测量各种协变量，以进一步增强对 发展趋势。目标1是确定早期认知下降（情节记忆，执行功能， 语音记忆，表达词汇，接受语法）；目标2是确定其他的变化 与衰老和/或向AD发展有关的域（例如，适应性行为，适应不良 行为，步态和心理速度）；目标3是将观察到的认知和行为改变链接到 MCI的症状（例如，仪器测量的日常定向，浓度，基本功能） 例如修改后的迷你政府考试。拟议的研究将通过识别 在广泛的措施中，DS的独特年龄范围内的发展趋势（尤其是下降）。 未来的方向包括延长纵向时间范围并添加淀粉样蛋白/TAU措施以更好 解释为与广告相关是否相关。