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) 是智力障碍最常见的遗传原因，大约七百分之一的人患有唐氏综合症患有 DS 的婴儿存在过早认知能力下降和阿尔茨海默病发病率增加的高风险。几乎所有 30 岁以上的 DS 患者都具有 AD 神经病理学特征。 DS 30 至 40 岁之间，某些认知功能会下降。岁，并且这种下降可以预测后来的 AD 诊断，但很少有纵向研究对此进行了检验青春期末期和成年早期患有 DS 的年轻人可能已经开始表现出来。 AD 的神经病理学，但 AD 诊断本身极为罕见。唐氏综合症的早期认知衰退项目 (R01HD098179) 旨在识别表现出以下症状的认知技能： DS 患者在青春期后期到成年早期的早期衰退。在阿拉巴马大学 (UA) 和加州大学戴维斯分校 (UCD) 进行，将招生年龄为 15-25 岁的 DS 参与者并跟踪他们三年的目标。补充是在现有的母体 R01 的基础上添加神经影像学，从而有助于促进确定一组早期认知衰退的独特指标，并预示随后的认知衰退 DS 患者的 AD 神经影像标记物也将与血液生物标记物一起进行评估。对于通过第一个行政补充收集的 AD，本补充的目的 1 是获取。每个部位 30 名 DS 参与者的结构、弥散、灌注和静息态 fMRI 扫描（总共 60 名）使用旨在帮助智力障碍人士参与 MRI 研究的创新策略。成像将与从家长补助金收集行为数据的第一个时间点一致。 AD 的多定量模式解剖和血管神经影像生物标志物，包括皮质形态测量，海马亚区、白质微观结构与脑血管疾病、脑血流、使用加州大学戴维斯分校阿尔茨海默病中心开发的图像处理管道进行网络连接研究中心神经影像核心将评估与并发相关的神经影像生物标志物。认知和行为测量以及与血液生物标志物（例如血浆浓度）相关的 Aβ、tau 蛋白和神经丝轻链 (NfL) 母版 R01 的结论，神经影像学。生物标志物将被评估为认知能力下降的预测因子，通过母体 R01 在三年内进行评估 MRI 扫描后的一年内将提供量化的神经影像数据和原始图像。通过 INCLUDE 数据协调中心 (DCC) 与其他研究人员共享。 MRI 指数有可能大大提高神经认知、行为和血液的价值已经收集了衰退和风险指标。