Asymptomatic Carotid Stenosis: Cognitive Function and Plaque Correlates

描述（由申请人提供）： 颈动脉狭窄是动脉粥样硬化栓塞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深入研究的重点。认知功能障碍是一个更隐蔽的，但知之甚少的结果，在“无症状”颈动脉狭窄的患者谁没有遭受中风。认知功能描述了一个人如何产生和控制心理过程，如思考，学习和解决问题。这是一个重要的结果措施，影响病人的福祉和他们的能力，生活独立生产力的谎言。众所周知，颈动脉狭窄导致的脑卒中患者同时存在认知功能障碍。然而，无症状颈动脉狭窄患者的孤立性认知障碍尚未被发现，因此没有详细报道。 无症状颈动脉狭窄影响2-12%的人。美国有2340万退伍军人，至少有100万人（4.3%）患有无症状的颈动脉狭窄，并有认知障碍的风险。心血管健康研究的一项子集分析发现，32名无症状颈动脉狭窄患者中有34%的人认知能力下降。在本提案中，我们将定义颈动脉狭窄退伍军人的初始和进行性认知障碍的程度，这些退伍军人目前被标记为“无症状”，没有局灶性神经功能缺损（中风，短暂性脑缺血发作）。预防、延缓或减轻颈动脉狭窄患者认知功能障碍的方案将取决于认知功能障碍介质的识别。微栓塞性脑损伤和脑灌注不足与老年人的认知功能障碍有关。因此，斑块结构、斑块成分、微栓子计数、血清炎症标志物和脑灌注不足可能是无症状颈动脉狭窄患者认知功能受损的介质。作为这项建议的一部分，我们将确定颈动脉狭窄可能导致认知障碍的生物学机制。 本提案的目的是进行一项系统的、有充分把握度的研究，以测量无症状颈动脉狭窄患者的认知障碍程度、其对生活质量的影响及其潜在的病理生理机制。本研究的信息将确定颈动脉狭窄的意外发病率，并确定存在认知障碍风险的患者亚组。这将为今后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，以减少不必要的血运重建手术。 具体目标1将评估无症状颈动脉狭窄患者与无颈动脉狭窄但血管风险特征相似的年龄匹配对照组相比，认知功能是否存在差异。我们假设，在无症状颈动脉狭窄的患者中，50%的患者在2年内无卒中存活;与无狭窄的患者相比，总体和特定领域认知功能的变化将显着不同。本研究将招募284例受试者，并将以90%的把握度检测认知评分的临床显著差异。我们将使用一套专门开发的新型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认知功能障碍相关的斑块形态学、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、血清促炎标志物和脑灌注不足在2年随访期内均能介导认知功能下降。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2年时，无论斑块特征如何，认知障碍将与健康相关的生活质量指标降低相关。

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.