Long-term Cognitive Effects of Microembolization Associated with Carotid Stenting

描述（由申请人提供）：中风是导致永久性残疾的最常见原因，在工业化国家仍然是第三大死亡原因。颈动脉内膜切除术（CEA）和支架植入术（CAS）已被证明是有效的卒中预防。然而，只有临床上明显的栓塞被评估为结果测量；亚临床微栓子尚未得到充分评估。一些研究证实，尽管没有临床症状，但在CAS期间扩散加权MRI （DWI）上显示的微栓子是常见的。迄今为止，微栓子的临床意义及其对认知功能的长期影响在很大程度上是未知的。为了阐明这些重要问题，我们建议在两个学术中心使用多学科团队方法进行深入的纵向调查。我们的中心假设是，亚临床微栓塞减缓了CAS后认知变化的程度，微栓塞本身的发展与患者和手术相关因素有关。具体目标1：确定DWI异常发展对亚临床微栓子患者认知功能短期和长期变化的临床意义；专项目标2：评估CAS术后亚临床微栓塞患者的危险因素；具体目标3：确定导致CAS过程中与手术相关的亚临床微栓塞的技术因素。研究者和合作者在颈动脉疾病（WZ， RLD， MGD），脑成像（BL， AR， ZG）和认知功能（AR， JY， LL）领域具有互补的专业知识和临床研究记录。统计分析将在Lazzeroni博士的咨询下进行，他是一位经验丰富的生物统计学家。通过这一提议和多学科团队专家的共同努力，我们希望了解三个关键问题：亚临床微栓塞是否与临床相关？它们会影响长期的神经认知功能吗？微栓子的危险因素是什么？了解这些基本问题对于通过适当的患者选择、更好的治疗方法和可能改进的介入技术来优化卒中预防策略至关重要。减少潜在的与微栓子相关的认知障碍也将通过减少与血管相关的痴呆对未来的公众健康产生重大影响。关于CAS治疗指南的持续争论提高了这项研究的紧迫性。该建议可能会改变我们目前的临床实践指南，为颈动脉介入治疗提供更好的结果测量。无论微栓子对认知的影响如何，危险因素分层为提高颈动脉介入治疗的质量提供了独特的机会。

DESCRIPTION (provided by applicant): Stroke is the most common cause of permanent disability, and remains the third leading cause of death in industrialized countries. Carotid endarterectomy (CEA) and stenting (CAS) have shown to be effective in stroke prevention. However, only clinically evident embolization has been evaluated as an outcome measure; subclinical microemboli have not been fully assessed. Several studies have confirmed that microemboli demonstrated on diffusion-weighted MRI (DWI) during CAS are common despite absence of clinical symptoms. To date, the clinical significance of microemboli and their long-term effects on cognitive function are largely unknown. To elucidate these important issues, we propose an intense longitudinal investigation using a multidisciplinary team approach at two academic centers. Our central hypothesis is that subclinical microembolization moderates the degree of cognitive changes following CAS and that development of microemboli themselves is associated with patients- and procedure- related factors. Three specific aims are proposed to address this urgent issue: Specific Aim 1: Determine the clinical significance of the development of DWI abnormalities for short- and long-term changes in cognitive function in patients with subclinical microemboli; Specific Aim 2: Evaluate patient risk factors for subclinical microembolization following CAS; and Specific Aim 3: Identify technical factors contributing to procedure-related subclinical microemboli during CAS. The investigators and collaborators have complementary expertise and a track record of clinical research in the areas of carotid disease (WZ, RLD, MGD), brain imaging (BL, AR, ZG), and cognitive function (AR, JY, LL). Statistical analyses will be conducted in consultation with Dr. Lazzeroni, an experienced biostatistician. Through this proposal and collaborative efforts of multidisciplinary team experts, we hope to understand three key questions: Are subclinical microemboli clinically relevant? Do they affect long-term neurocognitive function? What are the risk factors for microemboli? Understanding these fundamental issues is essential to optimizing our strategy in stroke prevention through proper patient selection, a better treatment approach, and possible refinement in interventional techniques. Reduction of potentially microemboli-associated cognitive impairment will also have a significant impact on future public health by decreasing vascular-related dementia. Ongoing debates regarding the treatment guideline for CAS raise the urgency of this study. The proposal may change our current clinical practice guideline by providing a better outcome measure for carotid interventions. Regardless of the cognitive effects of microemboli, risk factor stratification represents a unique opportunity for quality improvement in carotid interventions. PUBLIC HEALTH RELEVANCE: Subclinical microemboli are common during carotid artery stenting (CAS) procedures for patients with high-grade stenoses despite absence of neurologic symptoms. Our goal is to evaluate long-term cognitive effects of, and risk factors for, microemboli through a multidisciplinary longitudinal approach, and our long-term goal is to optimize strategies in stroke prevention and to improve future public health by reducing embolization-related cognitive impairment. The proposal may change our current clinical practice by providing a better outcome measure for carotid interventions.