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).

抽象的 脑小血管疾病（CSVD）在很大程度上加重了全球痴呆症的负担。由于血管疾病既可以预防又可以安全治疗，因此干预措施在减轻痴呆症负担方面具有巨大潜力。然而，需要更多的研究来开发合适的脑小血管对认知障碍和痴呆（VCID）影响的生物标志物。美国国家神经疾病和中风研究所 (NINDS) 支持 MarkVCID 计划，以推进七个站点和一个协调中心的 VCID 生物标志物的识别和验证。作为一个贡献站点，我们的团队领导了两种候选生物标志物的开发，帮助定义和协调所有协议，并通过从单个站点招募最大的西班牙裔样本来加入多站点验证。在这项提案中，我们力求将德克萨斯州南部更多元化的人口纳入其中，包括来自休斯顿和圣安东尼奥的西班牙裔和非裔美国人、中风和痴呆症诊所、初级保健和人口研究。我们进一步建议对基因组流行病学心脏和衰老研究队列 (CHARGE) 联盟的四个队列的丰富数据集中的候选生物标志物进行额外验证，这些队列拥有遗留数据（MRI、痴呆）和生物样本（血浆、血清、脑尸检）。作为 MarkVCID 网站，我们的目标是在不同样本中对 CSVD 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 55 岁以上患有主观认知障碍、轻度认知障碍或推测的血管病因早期痴呆的参与者，并在 5 年随访期间保留至少 320 名参与者；约 60 人将进入 UH3 阶段，并将进行 7 年的随访。我们将按照 MarkVCID 联盟 UH2/UH3 阶段制定的方案进行全面检查，收集病史、生物样本（血液、CSF）、影像学（具有脑血管反应性的 MRI、光学相干断层扫描血管造影）和神经心理学数据（认知，CDR）。我们将进行后续检查，通过临时电话筛查认知状态，并通过共识会议进行持续痴呆症监测。此外，我们将向同意的参与者提供脑部尸检，以评估 VCID 生物标志物的临床病理相关性。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、生物样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人员共享。我们的团队将拥有强大的领导能力，包括 UH3 Seshadri、Fornage（多个 PI）、Tracy（Co-I）、Tracy（Co-I）、一位久经考验的年轻 Co-I（现在接任联系人 PI（Satizabal））以及一位出色的中风试验领导者（Savitz）。