Multiethnic Validation of VCID biomarkers in South Texas

德克萨斯州南部 VCID 生物标志物的多种族验证

• 批准号: 10611823
• 负责人: MYRIAM FORNAGE
• 金额: $ 119.2万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611823
• 关键词: Multiethnic; Validation; VCID; biomarkers; South

ABSTRACT Cerebral small vessel disease (CSVD) contributes considerably to the global burden of dementia. As vascular diseases can be both prevented and safely treated, there is a great potential for interventions to reduce the burden of dementia. However, more research is needed to develop suitable biomarkers of cerebral small vessel contributions to cognitive impairment and dementia (VCID). The National Institute of Neurological Disorders and Stroke (NINDS) has supported the MarkVCID initiative to advance the identification and validation of biomarkers for VCID across seven sites and a coordinating center. As one contributing site, our team has led the development of two candidate biomarkers, helped define and harmonize all protocols, and joined multisite validation with the recruitment of the largest Hispanic sample from a single site. In this proposal, we seek to include a more diverse population across South Texas, including Hispanic and African Americans, from Houston and San Antonio, stroke and dementia clinics, primary care, and population studies. We further propose additional validation of candidate biomarkers in the rich datasets of four cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium that have legacy data (MRI, dementia) and biospecimens (plasma, serum, brain autopsy). As a MarkVCID site, we aim to perform a comprehensive, longitudinal validation of candidate biomarkers of CSVD in a diverse sample. We aim to recruit 400 participants over age 55 years with subjective cognitive complaints, mild cognitive impairment, or early dementia of presumed vascular etiology and retain at least 320 of them over the 5-year follow-up; ~60 will be persons seen in the UH3 phase and will have 7 years of follow- up. We will perform a comprehensive examination to collect medical history, biospecimens (blood, CSF), imaging (MRI with cerebrovascular reactivity, optical coherence tomography angiography), and neuropsychological data (cognition, CDR) following the protocols developed during the UH2/UH3 phases of the MarkVCID consortium. We will perform a follow-up examination with interim phone screenings for cognitive status and continuous dementia surveillance via consensus conferences. Further, we will offer brain autopsies to consenting participants for the assessment of clinicopathological correlates of VCID biomarkers. We will measure selected fluid and imaging biomarkers following established kit protocols and perform longitudinal clinical validation of biomarkers according to their pre-specified hypotheses. Finally, we will perform additional validation in four cohorts of the CHARGE consortium. Data, biospecimens, and results will be shared with the consortium and external qualified investigators through the designated MarkVCID coordinating center. Our team will have strong leadership with the PIs of the UH3 Seshadri, Fornage (multiple PI), Tracy (Co-I), a proven, young Co-I now taking over as Contact PI (Satizabal), and the addition of an exceptional stroke trials leader (Savitz).

摘要 脑小血管疾病（CSVD）在很大程度上增加了痴呆症的全球负担。由于血管疾病既可以预防又可以安全治疗，因此干预措施在减少痴呆症负担方面具有很大的潜力。然而，还需要更多的研究来开发合适的生物标志物，脑小血管对认知障碍和痴呆（VCID）的贡献。美国国家神经疾病和中风研究所（NINDS）支持MarkVCID倡议，以推进七个研究中心和一个协调中心的VCID生物标志物的鉴定和验证。作为一个贡献的网站，我们的团队已经领导了两个候选生物标志物的开发，帮助定义和协调所有协议，并加入了多站点验证与招聘最大的西班牙裔样本从一个单一的网站。在这项提案中，我们寻求包括整个南德克萨斯州更多样化的人口，包括西班牙裔和非洲裔美国人，来自休斯顿和圣安东尼奥，中风和痴呆症诊所，初级保健和人口研究。我们进一步提出了在基因组流行病学（CHARGE）联盟中心脏和衰老研究队列的四个队列的丰富数据集中对候选生物标志物进行额外验证，这些数据集具有遗留数据（MRI，痴呆）和生物标本（血浆，血清，脑尸检）。作为MarkVCID网站，我们的目标是在不同的样本中对CSVD的候选生物标志物进行全面的纵向验证。我们的目标是招募400名年龄在55岁以上的受试者，这些受试者有主观认知主诉、轻度认知障碍或假定血管病因的早期痴呆，并在5年随访期间保留其中至少320名受试者;约60名受试者将在UH 3期接受观察，并将接受7年随访。我们将根据MarkVCID联盟UH 2/UH 3阶段制定的方案进行全面检查，以收集病史、生物标本（血液、CSF）、成像（脑血管反应性MRI、光学相干断层扫描血管造影）和神经心理学数据（认知、CDR）。我们将进行随访检查，通过共识会议进行认知状态的临时电话筛查和持续痴呆监测。此外，我们将为同意的参与者提供脑尸检，以评估VCID生物标志物的临床病理学相关性。我们将按照既定的试剂盒方案测量选定的液体和成像生物标志物，并根据其预先指定的假设对生物标志物进行纵向临床验证。最后，我们将在CHARGE联盟的四个队列中进行额外的验证。数据、生物标本和结果将通过指定的MarkVCID协调中心与联盟和外部合格研究者共享。我们的团队将拥有强大的领导力，UH 3 Seshadri的PI，Fornage（多个PI），Tracy（Co-I），一位经过验证的年轻Co-I现在接任Contact PI（Satizabal），以及一位杰出的中风试验领导人（Savitz）。