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.

抽象的 许多研究表明，不仅鉴定颈动脉的存在的临床意义 闭塞性疾病，但在生化或功能上可能产生的动脉粥样硬化斑块 用于识别高危受试者的栓子。我们以前已经证明了我们的血管生物标志物，即 颈动脉菌株指数可检测到栓塞风险的不稳定牌匾，从而轻度认知 损害（MCI）可能会迅速发展为阿尔茨海默氏病（AD）和与阿尔茨海默氏症相关 痴呆症（ADRD）。在此补充中，我们建议获取初步数据以进一步评估血管 使用我们的应变指数与AD/ADRD的关系以识别不稳定的斑块和临床前动脉粥样硬化 使用颈动脉内膜媒体厚度（CIMT）可能会导致MCI。 在我们的第一个目标中，认知测试，经颅多普勒（TCD），经颅色编码多普勒（TCCD） 将对两名颈动脉内膜切除术（CEA）患者进行Lagrangian颈动脉菌株成像（LCSI）（LCSI） 以及一群处于危险的志愿者。这些结果将得到三分之二的验证和称赞 尺寸（3D）颈动脉磁共振成像（MRI）。此外，我们还将比较应变指数， Microemboli，对地面真理的脑灌注不足，即切除的斑块的3D组织病理学。我们的 先前的结果表明，无症状和有症状的CEA患者均存在逆 应变指数与执行认知功能之间的关系。我们假设这是由于沉默 中风和微栓塞导致执行功能下降。有症状的CEA患者 在其他认知领域（例如记忆，视觉空间和语言）中证明了下降。 我们的第二个目标将重点放在临床前动脉粥样硬化上，同一组高风险志愿者 控件是年龄和性别匹配的志愿者。我们将将CIMT测量与TCD相关联 该队列上的血管菌株指数和可能的MCI认知测试。基线CIMT已经 在先前的研究中，证明可以预测认知障碍和执行功能不佳 然后可以发展为广告。我们的结果将能够评估斑块沉积和 血管刚度确定可能建立血管衰老标准的偏差。逆转干预措施 然后可以规定血管衰老，例如生活方式修改和常见的医疗疗法。 验证我们的结果将促进使用实时非侵入性超声作为筛选工具 确定容易受到可能导致AD的轻度血管认知障碍的受试者。