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.

项目摘要/摘要： 小血管相关的血管贡献对认知障碍和痴呆（VCID）是老年人认知功能障碍的第二主要原因。但是，仍然缺乏适合使用的与VCID相关的关键血管过程的定量生物标志物，这些血管过程仍然缺乏临床试验中的终点。本应用的目标是1）参与NINDS选择多达六个生物标志物的多站点临床验证，这是通过对各种各样的所有人的认知障碍和/或早期症状的认知损伤和痴呆症可能与小血管疾病相关的纵向症状的纵向研究； 2）如果选择CVR生物标志物进入下一篇研究研究，则领导所有室中脑血管反应性（CVR）生物标志物的多部位临床验证。 本申请是RFA-NS-16-020下的UH2/3 NS100588的续订。 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）在UH2阶段，我们与其他站点合作，将MRI，生物流体，临床和神经心理学指标标准化，并在我们所在地本地提出的其他地点提出的候选生物标志物； 3）在UH3阶段，我们参加了由Ninds批准的生物标志物的多站点工具和生物学验证。 4）在UH3阶段，我们领导了CVR候选生物标志物的多站点仪器和生物学验证。重要的是，我们的网站具有执行目前正在考虑的11种生物标志物中的任何一个必要的科学专业知识和设备； 5）我们参加了所有财团的所有活动，例如年度会议，委员会会议和电话。 在本应用程序中，我们提出了四个具体目标。 AIM 1将招募220名各种各样的所有人的参与者，这些参与者在该项目的前两年中在美国的临床环境中是典型的，并收集了NINDS批准的生物标志物措施。 AIM 2将在该项目的后三年中至少有200名参与者进行纵向随访。 AIM 3将提供意见并参与整个财团的活动，例如在委员会中任职，讨论协议，参加和展示年度会议，参与多站点的数据处理和验证，以及与财团内外的研究人员共享数据和生物测量。在AIM 4中，如果选择CVR进入下一阶段，则我们将领导脑部反应性（CVR）生物标志物的多部位临床验证。 影响：该项目完成后，我们将开发一套VCID生物标志物，这些标志物已准备好用于VCID的未来临床试验，包括大型III期试验。