Neurocognitive Impairment Assessment in Symptomatic Carotid Occlusion Recanalized Endovascularly: NIA SCORE

症状性颈动脉闭塞血管内再通的神经认知损伤评估：NIA SCORE

• 批准号: 10634259
• 负责人: David M. Hasan
• 金额: $ 114.78万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10634259
• 关键词: Adult; Affect; Age; Alzheimer' s Disease; Amygdaloid structure; Anatomy; Angiography; Angioplasty; Area; Arteries; Atherosclerosis; Biological Markers; Blood Vessels; Blood flow; Bypass; Caliber; Carotid Arteries; Carotid Endarterectomy; Cerebrovascular Circulation; Cerebrum; Cervical; Classification; Clinical; Clinical Trials; Cognitive; Creatine; Data; Dementia; Development; Enrollment; Failure; Hippocampus (Brain); Hybrids; Impaired cognition; Incidence; Internal carotid artery structure; Intervention; Ipsilateral; Ischemic Stroke; Lesion; Limbic System; Magnetic Resonance Imaging; Measures; Medical; Meta-Analysis; Methods; Minor; N-acetylaspartate; Natural History; Neurocognitive Deficit; Neuropsychology; Outcome; Outcome Measure; Oxygen; Patients; Perfusion; Phase; Pilot Projects; Randomized; Recording of previous events; Recurrence; Resolution; Risk; Rupture; Spectrum Analysis; Stents; Stroke; Techniques; Testing; Time; Transient Ischemic Attack; Vascular Dementia; arm; artery occlusion; base; cerebral blood volume; cognitive function; cognitive testing; cohort; executive function; human data; improved; male; open label; prospective; radiological imaging; safety and feasibility; specific biomarkers; success

Project Summary: Complete occlusion of the internal carotid artery (COICA) by atherosclerotic disease causes approximately 15%–25% of ischemic strokes in the carotid artery distribution. Additionally, 40% of subjects with COICA who present with transient ischemic attacks and 70% of COICA who present with stroke have cognitive decline with significantly increased risk of vascular dementia and Alzheimer's' disease with time. Our group and others have used an alternative approach to revascularize subjects with COICAs. These studies showed the feasibility and safety of using endovascular angioplasty and stenting (EAS) and/or hybrid of both carotid enterectomy (CEA) and EAS to restore cerebral flow to the ipsilateral hemisphere of the COICA. Furthermore, our group devised a new angiographic and anatomic classification to upfront predict the success of revascularization using these techniques. This classification was tested in 2 pilot studies and the results showed robust plausibility to predict upfront the percentage of success anticipated in revascularizing these lesions using these techniques. In addition, 3 groups including ours showed that revascularization using these techniques restored cerebral blood flow to the ipsilateral hemisphere of the COICA evident of normalization of mean transient time (MTT) on CT perfusion (CTP) and significant improvement in the cognitive function. EAS and hybrid technique restore the caliber of the cervical ICA and therefore, the blood flow to all involved vessels with clear evidence of complete resolution of penumbra and normalization of MTT on CTP. This could provide an explanation for the marked improvement of cognitive function. Best medical management for this cohort maybe sufficient to reduce the risk of recurrent strokes and/or TIAs but not enough to improve executive and cognitive function and minimize the accelerated risk of vascular dementia and AD with time. This creates a clinical gap and a must need of an alternative approach to help this cohort. Therefore, we leverage our data and others to test the primary hypothesis below: Primary Hypothesis: Revascularizing symptomatic COICA using endovascular techniques (or Hybrid of carotid endarterectomy and endovascular techniques) will significantly improve cognitive outcome. To test this hypothesis we will examine these objectives: Primary Objective: To test the hypothesis that endovascular revascularization of COICA improves significantly cognitive function measured by Montreal Cognitive Assessment (MoCA) test. Secondary Objectives: To test the hypothesis that subjects with symptomatic COICAs and mild/moderate cognitive dysfunction have the following biomarkers: A) Large penumbra (≥50 ml) measured by mismatch volume of cerebral blood flow (CBF) & MTT on CTP, B) Presence of lactate and decreased N-acetylaspartate to creatine (Naa/Cr) in the watershed area (specifically centrum semiovale) on MRI-spectroscopy, and C) Decreased volumes of the hippocampus and amygdala on MRI.

项目概要： 动脉粥样硬化性疾病导致颈内动脉（COICA）完全闭塞 大约15%-25%的缺血性中风发生在颈动脉分布区。此外，40%的受试者 COICA患者中有短暂性脑缺血发作，70%的COICA患者中有卒中， 认知能力下降，血管性痴呆和阿尔茨海默病的风险随时间显著增加。 我们的小组和其他人已经使用了一种替代方法来重建COICA受试者的血运。这些 研究表明，使用血管内血管成形术和支架植入术（EAS）和/或 颈动脉内膜切除术（CEA）和EAS以恢复COICA同侧半球的脑血流。 此外，我们的小组设计了一种新的血管造影和解剖分类，以预先预测成功 使用这些技术进行血运重建。该分类在2项试点研究中进行了测试，结果 显示出强大的可预测性，可以提前预测这些患者的血运重建预期成功率。 使用这些技术。此外，包括我们在内的3组显示，使用这些药物进行血运重建 这些技术恢复了COICA同侧半球的脑血流，这证明了COICA的正常化。 CT灌注（CTP）的平均瞬态时间（MTT）和认知功能的显著改善。 EAS和混合技术恢复了颈部伊卡的口径，因此，所有 有明确证据表明，CTP上的半暗带完全消退，MTT正常化。 这可能为认知功能的显著改善提供了解释。 该队列的最佳医疗管理可能足以降低复发性卒中的风险和/或 短暂性脑缺血发作，但不足以改善执行和认知功能，并最大限度地减少血管性脑缺血的加速风险 老年痴呆症和AD这就造成了一个临床差距，必须需要一种替代方法来帮助解决这个问题。 队列。因此，我们利用我们的数据和其他数据来测试以下主要假设： 主要假设：使用血管内技术（或混合）对症状性COICA进行血运重建 颈动脉内膜切除术和血管内技术）将显着改善认知结果。 为了验证这一假设，我们将研究这些目标： 主要目的：检验COICA血管内血运重建改善 通过蒙特利尔认知评估（莫卡）测试测量的显著认知功能。 次要目的：检验以下假设：患有症状性COICA和轻度/中度COICA的受试者 认知功能障碍具有以下生物标志物：A）通过不匹配测量的大半暗带（≥50 ml） 脑血流量（CBF）和CTP上的MTT，B）乳酸盐和N-乙酰天冬氨酸减少的存在 在MRI光谱上，分水岭区域（特别是半卵圆中心）的肌酸（Naa/Cr），以及C） MRI显示海马体和杏仁核体积减少。