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

基本信息

批准号：
10369339
负责人：
MYRIAM FORNAGE
金额：
$ 241.28万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-30 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10369339
关键词：
African American Age Aging American Angiography Autopsy Biological Markers Blood Blood Platelets Blood Vessels Blood specimen Brain Categories Cerebral small vessel disease Cerebrospinal Fluid Cerebrum Clinic Clinical Clinical Trials Cognition Cognitive Collaborations Consensus Consent Data Data Set Dementia Development Diagnosis Disease Enrollment Epidemiology Ethnic group Etiology European Face Fostering Framingham Heart Study Genetic Goals Heart Hispanic Americans Hispanics Image Impaired cognition Intervention Leadership Liquid substance Magnetic Resonance Imaging Measures Medical History Mexican Americans Microvascular Dysfunction Modification Monitor National Institute of Neurological Disorders and Stroke Neuropsychology Not Hispanic or Latino Optical Coherence Tomography Outcome Participant Persons Pharmacodynamics Phase Phenotype Plasma Population Heterogeneity Population Study Primary Health Care Protocols documentation Race Renal function Research Research Personnel Risk Sampling Site South Texas Specific qualifier value Stroke Subgroup Telephone Validation Vascular Diseases biobank biomarker validation brain tissue candidate marker candidate validation cerebrovascular cohort design digital pathology follow-up genomic epidemiology imaging biomarker mild cognitive impairment multi-ethnic multidisciplinary neuropathology population based prevent prognostic programs recruit research clinical testing stroke trials symposium therapy development vascular cognitive impairment and dementia vascular contributions vascular risk factor

项目摘要

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）对全球痴呆症负担产生了很大贡献。由于可以预防和安全治疗血管疾病，因此干预措施有很大的潜力来减轻痴呆症的负担。但是，需要更多的研究来开发对认知障碍和痴呆症（VCID）的脑小血管贡献的合适生物标志物。美国国家神经系统疾病与中风研究所（NINDS）支持了MarkVCID计划，以推动跨七个地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个候选生物标志物的开发，帮助定义和协调所有协议，并通过招募了单个站点的最大西班牙裔样本，并加入了多站点验证。在此提案中，我们试图在南德克萨斯州包括更多的人口，包括西班牙裔和非裔美国人，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。我们进一步提议在具有遗产数据（MRI，痴呆症）和生物测量（Plasma，plasma，plasma，plasma，plassma，serum，brain Autopsy）的基因组流行病学（CHALL）联盟中的四个队列和衰老研究中的四个队列和衰老研究中的候选生物标志物的进一步验证。作为标记的站点，我们旨在在多样化的样本中对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55岁以上的400名参与者，具有主观认知障碍，轻度认知障碍或假定血管病因的早期痴呆症，并在5年的随访中保留了其中至少320个；〜60将是在UH3阶段看到的人，并将有7年的随访。我们将进行全面的检查，以收集病史，生物传感（血液，CSF），成像（具有脑血管反应性的MRI，光学相干性层析成像血管造影）和神经心理学数据（认知，CDR，CDR）在UH2/UH2/UH3期间开发的方案。我们将通过共识会议进行临时手机筛查和连续的痴呆症监测，进行后续检查。此外，我们将提供大脑尸检，以同意参与者评估VCID生物标志物的临床病理学相关性。我们将根据既定的套件方案来测量选定的流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，我们将在四个联盟联盟中进行其他验证。数据，生物测量和结果将通过指定的MarkVCID协调中心与财团和外部合格研究者共享。我们的团队将在UH3 Seshadri，Fornage（多个PI），Tracy（Co-I）的PI上领导着强大的领导才能，这是一个经过验证的年轻Co-I现在接任Contact Pi（Satizabal），并增加了一名出色的中风试验领导人（Savitz）。