Early Cognitive Decline in Down Syndrome – Neuroimaging Supplement

唐氏综合症的早期认知能力下降 – 神经影像补充品

基本信息

批准号：
10670637
负责人：
FRANCES A CONNERS
金额：
$ 40.43万
依托单位：
UNIVERSITY OF ALABAMA IN TUSCALOOSA
依托单位国家：
美国
项目类别：
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/10670637
关键词：
Administrative Supplement Adolescence Adolescent and Young Adult Adult Age Age-Years Alabama Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer’s disease biomarker Amyloid beta-Protein Amyloid beta-Protein Precursor Anatomy Behavioral Biological Markers Blood Blood Vessels Blood specimen California Cerebrovascular Circulation Cerebrovascular Disorders Cerebrovascular system Chromosome 21 Clinical Cognitive Data Data Collection Data Coordinating Center Developmental Course Diffusion Disease Progression Down Syndrome Elderly Enrollment Episodic memory Etiology Exhibits Future Genes Genetic Goals Hippocampus (Brain)Image Impaired cognition Incidence Individual Infant Intellectual functioning disability Life Light Link Longitudinal Studies MRI Scans Magnetic Resonance Imaging Measures Medial Memory Nerve Degeneration Neurocognitive Neurofibrillary Tangles Parents Participant Perfusion Plasma Process Research Research Personnel Rest Risk Scanning Secure Senile Plaques Short-Term Memory Site Symptoms Temporal Lobe Thick Time Universities Vocabulary Water White Matter Hyperintensity aged base behavior measurement cognitive function cognitive performance cognitive skill design diffusion weighted early detection biomarkers emerging adult entorhinal cortex executive function functional MRI scan functional decline high risk image processing imaging study indexing innovation morphometry multimodality neurofilament neuroimaging neuroimaging marker neuropathology overexpression parent grant parent project phonology premature recruit relating to nervous system segregation tau Proteins virtual white matter

项目摘要

ABSTRACT Down syndrome (DS) is the most common genetic cause of intellectual disability and occurs in about 1 in 700 infants. Adults with DS are at high risk for premature cognitive decline and increased incidence of Alzheimer’s disease (AD). Virtually all individuals with DS over 30 years of age have the hallmark AD neuropathology of beta amyloid plaques and neurofibrillary tangles. Certain cognitive functions decline in DS between 30 and 40 years old and the decline is predictive of later AD diagnosis, yet few longitudinal studies have examined younger individuals. Individuals with DS in late adolescence and early adulthood likely have begun to exhibit neuropathology of AD, but AD diagnosis itself is extremely rare. The broad, long-term objective of the parent project, Early Cognitive Decline in Down Syndrome (R01HD098179), is to identify cognitive skills that show early decline in individuals with DS during late adolescence into early adulthood. This longitudinal study, conducted at the University of Alabama (UA) and the University of California Davis (UCD), will enroll participants with DS aged 15-25 years and follow them for three years. The goal of the proposed supplement is to add neuroimaging to the existing parent R01, and thereby help to contribute to the identification of a set of unique indicators of early cognitive decline and that foreshadow subsequent AD in individuals with DS. Neuroimaging markers will also be evaluated in conjunction with blood biomarkers for AD collected through the first administrative supplement. Aim 1 of the present supplement is to acquire structural, diffusion, perfusion, and resting state fMRI scans in 30 participants with DS at each site (60 total) using innovative strategies designed to help individuals with intellectual disability participate in MRI research. Imaging will coincide with the first time point of behavioral data collection from the parent grant. Aim 2 is to quantify multi-modal anatomical and vascular neuroimaging biomarkers of AD, including cortical morphometry, hippocampal subfields, white matter microstructure and cerebrovascular disease, cerebral blood flow, and network connectivity using image processing pipelines developed by the UC Davis Alzheimer’s Disease Research Center Neuroimaging Core. Neuroimaging biomarkers will be assessed in relation to concurrent cognitive and behavioral measures as well as in relation to blood biomarkers such as plasma concentrations of Aβ, tau protein, and neurofilament light chains (NfL). At the conclusion of the parent R01, neuroimaging biomarkers will be evaluated as predictors of cognitive decline assessed through the parent R01 over a three- year period after the MRI scan. Quantified neuroimaging data and raw images will be made available for sharing with other researchers through the INCLUDE Data Coordinating Center (DCC). Adding AD-sensitive MRI indices has the potential to greatly enhance the value of the neurocognitive, behavioral, and blood-based indicators of decline and risk already being collected.

抽象的唐氏综合症（DS）是智力残疾的最常见遗传原因，发生在700中的大约1个婴儿。 DS的成年人有高度认知能力下降和阿尔茨海默氏症事件增加的风险疾病（AD）。几乎所有30岁以上DS的人都具有标志性的AD神经病理学 β淀粉样蛋白斑块和神经原纤维缠结。 DS的某些认知功能在30到40之间下降多年来的下降和下降是对以后的AD诊断的预测，但很少有纵向研究检查年轻人。在青少年晚期和成年初患有DS的人可能已经开始展出 AD的神经病理学，但AD诊断本身极为罕见。父母的广泛，长期目标项目，唐氏综合症的早期认知能力下降（R01HD098179），是为了识别表现出的认知技能成年后青少年晚期的DS患者的早期下降。这项纵向研究，在阿拉巴马大学（UA）和加利福尼亚大学戴维斯分校（UCD）举行 DS年龄15-25岁的参与者跟随他们三年。提议的目标补充是将神经影像添加到现有的父母R01，从而有助于为识别一组早期认知下降的独特指标，随后预示了 DS的个体中的广告。神经影像标记也将与血液生物标志物一起评估对于通过第一笔行政补充收集的广告。目前的AIM 1是获取在每个站点的30名参与者中，结构，扩散，灌注和静止状态fMRI扫描（总共60个）使用旨在帮助智障人士参与MRI研究的创新策略。成像将与父母赠款的行为数据收集的第一个时间相吻合。目标2是量化AD的多模式解剖学和血管神经影像学，包括皮质形态计量学，海马子场，白质微观结构和脑血管疾病，脑血流和使用图像处理管道的网络连通性由加州大学戴维斯加州大学阿尔茨海默氏病开发研究中心神经影像核心。神经成像生物标志物将与并发有关认知和行为措施以及与血液生物标志物（如血浆浓度）有关 Aβ，tau蛋白和神经丝链（NFL）。在父r01结束时，神经影像学生物标志物将被评估为通过母亲R01评估的认知下降的预测指标 MRI扫描后的一年。量化的神经影像数据和原始图像将用于通过包括数据协调中心（DCC）与其他研究人员共享。添加广告敏感 MRI指数有可能大大提高神经认知，行为和基于血液的价值已经收集了下降和风险的指标。