Early Cognitive Decline in Down Syndrome – Neuroimaging Supplement

摘要 唐氏综合症(DS)是导致智力残疾的最常见的遗传原因，大约每700人中就有1人发生 婴儿。患有DS的成年人过早认知能力下降和阿尔茨海默氏症发病率增加的风险很高 疾病(AD)。几乎所有30岁以上的DS患者都有显著的AD神经病理 β淀粉样斑块和神经原纤维缠结。DS患者在30至40岁之间某些认知功能下降 几岁，而且下降预示着以后的AD诊断，但很少有纵向研究检查 更年轻的个体。青春期晚期和成年期早期的DS患者可能已经开始表现出 阿尔茨海默病的神经病理，但AD本身的诊断极为罕见。父母的广泛、长期的目标 项目，唐氏综合症的早期认知下降(R01HD098179)，是为了识别显示出 患有DS的个体在青春期晚期到成年早期的早期衰退。这项纵向研究， 在阿拉巴马大学(UA)和加州大学戴维斯分校(UCD)进行，将招收 患有DS的参与者年龄在15-25岁，并随访三年。建议的目标是 补充是将神经成像添加到现有的父母R01中，从而有助于 确定一套独特的早期认知衰退指标，并预示着随后的 在患有DS的个体中的AD。神经成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副刊收集的AD。本补编的目标1是获得 30名参与者进行了结构、扩散、灌注和静息状态的fMRI扫描，每个部位都有DS(共60例)。 使用旨在帮助智障人士参与核磁共振研究的创新战略。 成像将与从父母赠款收集行为数据的第一个时间点一致。目标2是 量化AD的多模式解剖和血管神经成像生物标志物，包括皮质形态计量学， 海马亚区，白质微结构与脑血管疾病，脑血流，以及 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 研究中心神经成像核心。神经成像生物标记物将根据并发 认知和行为测量以及与血液生物标记物的关系，如血浆浓度 β、tau蛋白和神经丝轻链(NFL)。在家长R01结束时，神经成像 生物标志物将被评估为认知能力下降的预测因素，通过父母R01在三年内进行评估- 核磁共振扫描后的一年内。量化的神经成像数据和原始图像将提供给 通过Include数据协调中心(DCC)与其他研究人员共享。添加AD敏感型 MRI指标有可能极大地提高神经认知、行为和血液基础的价值 已经收集到的下降和风险指标。

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.