Validation of small vessel vascular contributions to cognitive impairment and dementia (VCID) biomarkers

验证小血管对认知障碍和痴呆 (VCID) 生物标志物的贡献

• 批准号: 10368371
• 负责人: MARILYN S. ALBERT
• 金额: $ 262万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10368371
• 关键词: African American; Alzheimer' s Disease; Asians; Biological; Biological Markers; Blood; Blood Vessels; Caucasians; Clinical; Clinical Trials; Cognitive; Consensus; Data; Data Analyses; Dementia; Diabetes Mellitus; Enrollment; Equipment; Event; Functional Imaging; Funding; Future; Goals; Hispanics; Hypertension; Image; Impaired cognition; Individual; Lead; Liquid substance; Longitudinal Studies; Longitudinal cohort study; Magnetic Resonance Imaging; Manuscripts; Measures; Memory; Microvascular Dysfunction; Mission; National Institute of Neurological Disorders and Stroke; Neuropsychology; Obesity; Participant; Persons; Phase; Population; Procedures; Process; Protocols documentation; Quality Control; Research; Research Personnel; Site; Smoking; Source; Standardization; Testing; Training; United States; Validation; Work; base; biomarker validation; candidate marker; cerebrovascular; clinical research site; cohort; computerized data processing; data sharing; experience; flexibility; follow up assessment; follow-up; human subject; hypercholesterolemia; imaging biomarker; indexing; meetings; mild cognitive impairment; neuroimaging; phase III trial; recruit; symposium; treatment center; vascular cognitive impairment and dementia; vascular risk factor

Project Summary/Abstract: Small-vessel-related vascular contributions to cognitive impairment and dementia (VCID) represent the second leading cause of cognitive dysfunction in older individuals. However, quantitative biomarkers indexing key vascular processes related to VCID that are suitable for use as endpoints in clinical trials are still lacking. The goals of the present application are to 1) participate in the multi-site clinical validation of up to six biomarkers selected by the NINDS through a longitudinal study of diverse all-comers with cognitive complaints and/or early symptomatic signs of cognitive impairment and dementia potentially associated with small vessel disease; 2) lead the multi-site clinical validation of cerebrovascular reactivity (CVR) biomarker in all-comers, if the CVR biomarker is selected to move onto the next-phase study. The present application is a Renewal of UH2/3 NS100588 under RFA-NS-16-020. As one of the funded participating sites of the above-mentioned RFA, hereafter referred to as MarkVCID I study, our team at JHU has made significant contributions to the Consortium: 1) In the UH2 phase, we developed a CVR MRI candidate biomarker and collected data to support its selection by the NINDS to become one of the eleven biomarkers that transited into the UH3 phase; 2) In the UH2 phase, we worked with other sites to standardize MRI, biofluid, clinical, and neuropsychological measures and implemented candidate biomarkers proposed by other sites locally at our site; 3) In the UH3 phase, we participated in the multi-site instrumental and biological validation of biomarkers approved by the NINDS; 4) In the UH3 phase, we led the multi-site instrumental and biological validation of the CVR candidate biomarker. Importantly, our site has the scientific expertise and equipment that are necessary to perform any of the 11 biomarkers currently under consideration; 5) We participated in all Consortium-wide activities such as annual conferences, committee meetings, and calls. In the present application, we propose four Specific Aims. Aim 1 will enroll 220 participants of diverse all-comers that are typical in clinical settings in the United States during the first two years of the project and collect the NINDS-approved biomarker measures. Aim 2 will conduct longitudinal follow-up in a minimum of 200 participants in the latter three years of the project. Aim 3 will provide inputs and participate in the Consortium-wide activities such as serving on committees, discussing protocols, attending and presenting in the annual conferences, participating in multi-site data processing and validation, and sharing data and biospecimens with researchers within and outside the Consortium. In Aim 4 we will lead multi-site clinical validation of cerebrovascular reactivity (CVR) biomarker if CVR is selected to move on to the next phase. Impact: Upon the completion of this project, we will have developed a set of VCID biomarkers that are ready for future clinical trials, including large phase III trials, of VCID.

项目概要/摘要： 小血管相关的血管对认知障碍和痴呆（VCID）的贡献是老年人认知功能障碍的第二大原因。然而，仍然缺乏定量生物标志物，其指示与VCID相关的、适合用作临床试验终点的关键血管过程。本申请的目标是1）通过对具有认知主诉和/或可能与小血管疾病相关的认知障碍和痴呆的早期症状体征的各种各样的所有来者的纵向研究，参与由NINDS选择的多达六种生物标志物的多地点临床验证; 2）如果选择脑血管反应性（CVR）生物标志物进入下一阶段研究，则在所有参与者中领导CVR生物标志物的多中心临床验证。 本申请是RFA-NS-16-020下的UH 2/3 NS 100588的更新。作为上述RFA（以下简称为MarkVCID I研究）的资助参与单位之一，我们在JHU的团队为联盟做出了重大贡献：1）在UH 2阶段，我们开发了CVR MRI候选生物标志物，并收集了数据，以支持NINDS选择其成为过渡到UH 3阶段的11个生物标志物之一; 2）在UH 2阶段，我们与其他研究中心合作，对MRI、生物流体、临床和神经心理学指标进行标准化，并在我们的研究中心实施其他研究中心提出的候选生物标志物; 3）在UH 3阶段，我们参与了NINDS批准的生物标志物的多中心仪器和生物学验证; 4）在UH 3阶段，我们领导了CVR候选生物标志物的多中心仪器和生物学验证。重要的是，我们的研究中心拥有执行目前正在考虑的11种生物标志物中的任何一种所需的科学专业知识和设备; 5）我们参加了所有联盟范围的活动，如年度会议，委员会会议和电话会议。 在本申请中，我们提出了四个具体目标。目标1将招募220名参与者，这些参与者来自不同的所有参与者，这些参与者在项目的前两年在美国的临床环境中是典型的，并收集NINDS批准的生物标志物指标。目标2将在项目的后三年对至少200名参与者进行纵向跟踪。目标3将提供投入并参与联合会范围内的活动，例如担任委员会成员，讨论议定书，出席年度会议并在会上发言，参与多地点数据处理和验证，并与联合会内外的研究人员分享数据和生物标本。在目标4中，如果选择CVR进入下一阶段，我们将领导脑血管反应性（CVR）生物标志物的多中心临床验证。 影响力：该项目完成后，我们将开发出一套VCID生物标志物，可用于未来的VCID临床试验，包括大型III期试验。