Asymptomatic Carotid Stenosis: Cognitive Function and Plaque Correlates

无症状颈动脉狭窄：认知功能和斑块相关

• 批准号: 8698365
• 负责人: Brajesh K Lal
• 金额: --
• 依托单位: BALTIMORE VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8698365
• 关键词: Address; Affect; Age; Architecture; Behavior Control; Biological; Blood; Blood Vessels; Blood flow; Brain; Brain Injuries; Caliber; Cardiovascular system; Carotid Artery Plaques; Carotid Stenosis; Cerebrum; Characteristics; Chemicals; Clinical; Cognitive; Cognitive deficits; Conscious; Country; Elderly; Focal Neurologic Deficits; Foundations; Future; Goals; Health; Hospitals; Imaging Techniques; Impaired cognition; Impairment; Independent Living; Individual; Investigation; Label; Learning; Measurement; Measures; Mediating; Mediator of activation protein; Mental Processes; Morbidity - disease rate; Morphology; Operative Surgical Procedures; Outcome; Outcome Measure; Patient Selection; Patients; Personal Satisfaction; Persons; Prevention; Problem Solving; Procedures; Process; Production; Quality of life; Recruitment Activity; Rehabilitation therapy; Reporting; Resources; Risk; Role; Serum; Stenosis; Stroke; Stroke prevention; Structure; Support System; Techniques; Testing; Thinking; Three-Dimensional Imaging; Transient Ischemic Attack; Ultrasonography; Veterans; cerebral hypoperfusion; clinically significant; cognitive change; cognitive function; cognitive rehabilitation; follow-up; health related quality of life; hemodynamics; improved; inflammatory marker; novel; particle; prevent; programs; randomized trial

DESCRIPTION (provided by applicant): Carotid artery stenosis is a well-known cause of atheroembolic stroke. Stroke prevention in these patients has been the focus of intense investigation. Cognitive impairment is a more insidious but poorly understood outcome in patients with "asymptomatic" carotid stenosis who have not suffered a stroke. Cognitive function describes how a person produces and controls mental processes such as thinking, learning, and problem solving. It is an important outcome measure that affects patient well-being and their ability to live independent productive lies. It is well-known that cognitive impairment coexists in patients with stroke from carotid stenosis. However, isolated cognitive deficits in patients with asymptomatic carotid stenosis have not been looked for, and have therefore not been reported in any detail. Asymptomatic carotid stenosis affects 2-12% of people. With 23.4 million veterans in the country, at least 1 million (4.3%) have asymptomatic carotid stenosis and are at risk for cognitive impairment. A subset analysis of the Cardiovascular Health Study found cognitive decline in 34% of 32 patients with asymptomatic carotid stenosis. In this proposal, we will define the extent of initial and progressive cognitive impairment in veterans with carotid stenosis who are currently labeled as "asymptomatic" in the absence of a focal neurologic deficit (stroke, transient ischemic attack). Programs to prevent, postpone, or mitigate cognitive impairment in patients with carotid stenosis will depend on the identification of mediators for cognitive impairment. Microembolic brain injury and cerebral hypoperfusion have been associated with cognitive impairment in elderly individuals. Therefore plaque architecture, plaque composition, microembolic counts, serum inflammatory markers, and cerebral hypoperfusion are likely mediators of impaired cognition in patients with asymptomatic carotid stenosis. As part of this proposal, we will identify the biological mechanisms by which carotid stenosis could result in cognitive impairment. The goal of this proposal is to perform a systematic, adequately powered study to measure the magnitude of cognitive impairment in asymptomatic carotid stenosis, its impact on quality of life, and its potential pathophysiological mechanisms. Information from this study will define an unsuspected morbidity of carotid stenosis and identify subsets of patients at risk for cognitive impairment. It will form the foundation for future studies on prevention, pre-emptive treatment, or rehabilitation of patients with carotid stenosis. It will also improve the selection of patients with carotid stenosis to decrease unnecessary revascularization procedures. Specific Aim 1 will assess if patients with asymptomatic carotid stenosis differ in cognitive function compared to age-matched controls without carotid stenosis but with similar vascular risk profiles. We hypothesize that in patients with asymptomatic carotid stenosis 50% who survive stroke free for 2 years; the change in overall and domain-specific cognitive function will be significantly different compared to those without stenosis. The study will recruit 284 subjects and will detect a clinically significant difference in cognitive score with 90% power. We will use a novel battery of cognitive tests specifically developed to address the unique issues relating to carotid stenosis. Specific Aim 2 will define plaque-morphometric, biologic, and hemodynamic characteristics that correlate with cognitive impairment in patients with asymptomatic carotid stenosis. We hypothesize that carotid plaque architecture, plaque composition, microembolic counts, serum pro-inflammatory markers, and cerebral hypoperfusion could each mediate cognitive decline over a 2-year follow-up period. We will implement a novel clinical 3D B-mode ultrasound imaging technique developed to obtain reliable serial plaque measurements. Specific Aim 3 will measure the impact of cognitive impairment on quality of life. We hypothesize that at 2 years, regardless of plaque features, cognitive impairment will correlate with a reduction in health-related quality of life measures.

描述(由申请人提供)： 颈动脉狭窄是动脉粥样硬化性中风的一个众所周知的原因。这些患者的卒中预防一直是密集调查的重点。认知障碍是一种更隐蔽但知之甚少的结果，在没有中风的“无症状”颈动脉狭窄患者中。认知功能描述了一个人如何产生和控制思维、学习和解决问题等心理过程。它是影响患者幸福感和独立生活能力的重要结果指标。众所周知，颈动脉狭窄导致的卒中患者存在认知功能障碍。然而，无症状性颈动脉狭窄患者的孤立认知障碍尚未被发现，因此没有任何详细的报道。无症状的颈动脉狭窄影响2-12%的人。在该国2340万退伍军人中，至少有100万人(4.3%)患有无症状的颈动脉狭窄，并面临认知障碍的风险。心血管健康研究的一个子集分析发现，在32名无症状颈动脉狭窄患者中，34%的人认知能力下降。在这项提案中，我们将定义患有颈动脉狭窄的退伍军人的初始和进展性认知障碍的程度，这些退伍军人目前被标记为在没有局灶性神经功能障碍(中风、短暂性脑缺血发作)的情况下是无症状的。预防、推迟或减轻颈动脉狭窄患者认知损害的计划将取决于认知损害介质的确定。脑微栓子损伤和脑低灌流与老年人的认知障碍有关。因此，斑块结构、斑块成分、微栓子计数、血清炎症标志物和脑低灌流可能是无症状性颈动脉狭窄患者认知损害的中介因素。作为这项提议的一部分，我们将确定颈动脉狭窄可能导致认知障碍的生物学机制。这项建议的目标是进行一项系统的、足够有力的研究，以衡量无症状颈动脉狭窄患者认知障碍的程度、对生活质量的影响及其潜在的病理生理机制。这项研究的信息将定义颈动脉狭窄的意外发病率，并确定有认知障碍风险的患者亚群。这将为未来颈动脉狭窄患者的预防、预防性治疗或康复研究奠定基础。它还将改善颈动脉狭窄患者的选择，以减少不必要的血管重建术。具体目标1将评估无症状颈动脉狭窄的患者与年龄匹配的无颈动脉狭窄但血管风险特征相似的对照组相比，认知功能是否存在差异。我们假设，在有无症状颈动脉狭窄的患者中，有50%的患者在卒中后2年内没有存活；与没有狭窄的患者相比，总体和领域特定认知功能的变化将有显着不同。这项研究将招募284名受试者，并将以90%的力量检测到认知分数在临床上的显著差异。我们将使用专门开发的一组新的认知测试来解决与颈动脉狭窄相关的独特问题。具体目标2将定义与无症状颈动脉狭窄患者的认知损害相关的斑块形态计量学、生物学和血流动力学特征。我们假设颈动脉斑块结构、斑块成分、微栓子计数、血清促炎标记物和脑低灌注量在两年的随访期内均可调节认知功能下降。我们将实施一种新的临床三维B型超声成像技术，以获得可靠的连续斑块测量。具体目标3将衡量认知障碍对生活质量的影响。我们假设，在两年后，不管斑块的特征如何，认知障碍将与健康相关的生活质量指标的降低相关。