Early Detection of Vascular Dysfunction Using Biomarkers from Lagrangian Carotid

摘要 大量研究已经证明，不仅识别颈动脉的存在具有临床意义 闭塞性疾病，但也有动脉粥样硬化斑块，这些斑块在生化或功能上可能会产生 用于识别高危对象的栓子。我们之前已经证明，我们的血管生物标记物，即 颈动脉张力指数能够检测到有可能进行栓塞术的不稳定斑块，因此可以进行轻度认知 损害(MCI)，然后可能迅速发展为阿尔茨海默病(AD)和阿尔茨海默病相关 痴呆(ADRD)。在本补充资料中，我们建议获得初步数据以进一步评估血管 应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 这可能导致使用颈动脉内中膜厚度(CIMT)的MCI。 在我们的第一个目标中，认知测试，经颅多普勒(TCD)，经颅彩色编码多普勒(TCD) 两位颈动脉内膜切除术(CEA)患者都将接受拉格朗日颈动脉应变成像(LCSI)。 以及一组高危志愿者的控制组。这些结果将由三个人验证和赞扬- 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，脑实质低灌注，即切除斑块的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患者都表现出相反的 应激指数与执行认知功能的关系。我们推测这是由于沉默造成的 中风和微栓子导致执行功能下降。有症状的CEA患者也 表现出其他认知领域的衰退，如记忆、视觉空间和语言。 我们的第二个目标，将专注于临床前动脉粥样硬化，针对同一组高危志愿者 对照组为年龄和性别匹配的志愿者。我们将CIMT测量与TCD、TCD相关联 和血管紧张指数对可能的MCI进行认知测试。基准CIMT一直是 在先前的研究中被证明是认知障碍和执行功能低下的预测性因素 然后可以进展到AD。我们的结果将使我们能够评估斑块沉积和 血管硬度，以确定偏差，可以建立血管老化标准。需要逆转的干预措施 然后，可以开出血管老化的处方，例如改变生活方式和常见的药物疗法。 我们结果的验证将促进实时无创超声作为筛查工具的使用 识别易患轻度血管认知损害的人类受试者，这可能导致阿尔茨海默病。

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.