Early Detection of Vascular Dysfunction Using Biomarkers from Lagrangian Carotid

使用拉格朗日颈动脉生物标志物早期检测血管功能障碍

• 批准号: 10490566
• 负责人: TOMY VARGHESE
• 金额: $ 35.99万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10490566
• 关键词: 3-Dimensional; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Arterial Fatty Streak; Atherosclerosis; Bilateral; Biochemical; Biological Markers; Blood Vessels; Brain; Cardiac; Carotid Artery Plaques; Carotid Atherosclerotic Disease; Carotid Endarterectomy; Cerebral Emboli; Cerebrovascular Circulation; Characteristics; Clinical; Code; Cognition; Cognitive; Color; Complement; Control Groups; Data; Dementia; Deposition; Detection; Deterioration; Development; Disease; Early Diagnosis; Embolism; Fostering; Frequencies; Gender; General Population; Grant; Histopathology; Human Volunteers; Hyperlipidemia; Hypertension; Image; Impaired cognition; Individual; Internal Carotid Artery Stenosis; Intervention; Language; Lead; Left; Life Style Modification; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Medical; Memory; Modeling; National Heart, Lung, and Blood Institute; Nerve Degeneration; Operative Surgical Procedures; Pathology; Patients; Physiologic pulse; Play; Research; Risk; Risk Factors; Role; Rupture; Scanning; Screening procedure; Side; Source; Specimen; Statistical Data Interpretation; Stroke; Subgroup; Testing; Therapeutic Embolization; Time; Tissues; Transcranial Doppler Ultrasonography; Ultrasonography; United States National Institutes of Health; Validation; Variant; Vascular Cognitive Impairment; Vascular Diseases; Visuospatial; Work; age related; atherosclerosis risk; base; carotid intima-media thickness; cerebral hemodynamics; cerebral hypoperfusion; cerebrovascular; clinically significant; cognitive function; cognitive performance; cognitive testing; cohort; executive function; high risk population; human subject; indexing; middle cerebral artery; mild cognitive impairment; mixed dementia; pre-clinical; pre-clinical assessment; prospective; screening; ultrasound; vascular risk factor; volunteer

Abstract Numerous studies have demonstrated the clinical significance of identifying not only presence of carotid occlusive disease but also atherosclerotic plaques that are biochemically or functionally likely to produce emboli for identifying at-risk subjects. We have previously demonstrated that our vascular biomarkers, namely carotid strain indices enable detection of unstable plaque at risk for embolization and thereby mild cognitive impairment (MCI) which could then rapidly progress to Alzheimer disease (AD) and Alzheimer related dementias (ADRD). In this supplement we propose to obtain preliminary data to further evaluate vascular relationships to AD/ADRD using our strain indices to identify unstable plaque and pre-clinical atherosclerosis that may lead to MCI using carotid intima-media thickness (CIMT). In our first Aim, cognitive testing, transcranial Doppler (TCD), transcranial color-coded Doppler (TCCD) and Lagrangian carotid strain imaging (LCSI) will be performed on both carotid endarterectomy (CEA) patients and a control group of at-risk volunteers. These results will be validated and complimented by three- dimensional (3D) carotid magnetic resonance imaging (MRI). In addition, we will also compare strain indices, microemboli, cerebral hypoperfusion to the ground truth, namely 3D histopathology of the excised plaque. Our prior results demonstrate that both asymptomatic and symptomatic CEA patients present with an inverse relationship between strain indices and executive cognitive function. We hypothesize that this is due to silent strokes and microemboli contributing to a decline in executive function. Symptomatic CEA patients also demonstrate decline across other cognitive domains such as memory, visuospatial and language. Our second Aim, will focus on pre-clinical atherosclerosis, on the same group of high-risk volunteers with controls being age and gender matched volunteers. We will correlate CIMT measurements to TCD, TCCD and vascular strain indices on this cohort to cognitive testing for possible MCI. Baseline CIMT has been demonstrated to be predictive for developing cognitive impairment and poor executive function in a prior study which can then progress to AD. Our results will enable assessment of variations in plaque deposition and vascular stiffness to determine deviations that could establish vascular aging criteria. Interventions to reverse vascular aging for example lifestyle modifications and common medical therapies can then be prescribed. Validation of our results will foster use of real-time noninvasive ultrasound as a screening tool for identifying human subjects susceptible to developing mild vascular cognitive impairment that could lead to AD.

摘要 许多研究已经证明了不仅识别颈动脉的存在的临床意义 闭塞性疾病以及动脉粥样硬化斑块，其在生物化学上或功能上可能产生 用于识别风险受试者的栓塞。我们之前已经证明了我们的血管生物标志物，即 颈动脉应变指数能够检测有栓塞风险的不稳定斑块， 这种损害（MCI）随后可迅速进展为阿尔茨海默病（AD）和阿尔茨海默病相关疾病， 痴呆症（ADRD）。在本补充中，我们建议获得初步数据，以进一步评估血管 使用我们的应变指数识别不稳定斑块和临床前动脉粥样硬化与AD/ADRD的关系 使用颈动脉内膜中层厚度（CIMT）可能导致MCI。 在我们的第一个目标，认知测试，经颅多普勒（TCD），经颅彩色编码多普勒（TCCD） 将对2例颈动脉内膜切除术（CEA）患者进行拉格朗日颈动脉应变成像（LCSI） 和一组高危志愿者的对照组。这些结果将得到三个方面的验证和补充- 三维（3D）颈动脉磁共振成像（MRI）。此外，我们还将比较应变指数， 微栓子，脑灌注不足，即切除斑块的3D组织病理学。我们 先前的研究结果表明，无症状和有症状的CEA患者都表现出相反的 紧张指数和执行认知功能之间的关系。我们假设这是由于沉默 中风和微栓子导致执行功能下降。症状CEA患者也 在其他认知领域，如记忆，视觉空间和语言方面表现出下降。 我们的第二个目标，将集中在临床前动脉粥样硬化，对同一组高风险的志愿者 对照组为年龄和性别匹配的志愿者。我们将把CIMT测量值与TCD、TCCD 和血管应变指数来进行可能的MCI的认知测试。基线CIMT已 在先前的研究中被证明是发展认知障碍和执行功能差的预测因素 然后可以发展为AD。我们的研究结果将能够评估斑块沉积的变化， 血管硬度，以确定可以建立血管老化标准的偏差。扭转局势的干预措施 血管老化例如生活方式的改变和普通的医学治疗可以被指定。 验证我们的结果将促进使用实时无创超声作为筛查工具， 鉴定易发生可导致AD的轻度血管性认知障碍的人类受试者。