Long-term Cognitive Effects of Microembolization Associated with Carotid Stenting

描述(申请人提供)：中风是导致永久性残疾的最常见原因，在工业化国家仍是第三大致死原因。颈动脉内膜剥脱术(CEA)和支架置入术(CAS)已被证明在预防中风方面是有效的。然而，只有临床上明显的栓塞术才被评估为一种结果衡量标准；亚临床微栓子还没有得到充分的评估。一些研究证实，尽管没有临床症状，但CAS期间弥散加权磁共振(DWI)显示的微栓子是常见的。到目前为止，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尚不清楚。为了阐明这些重要的问题，我们建议在两个学术中心使用多学科团队的方法进行密集的纵向调查。我们的中心假设是亚临床微栓塞术减缓了CAS后认知改变的程度，微栓子的发展本身与患者和手术相关的因素有关。为了解决这一紧迫问题，提出了三个具体目标：具体目标1：确定弥散加权成像异常的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；具体目标2：评估CAS术后亚临床微栓子的患者危险因素；以及具体目标3：确定在CAS过程中与操作相关的亚临床微栓子的技术因素。研究人员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)领域拥有互补的专业知识和临床研究记录。统计分析将与经验丰富的生物统计学家Lazzeroni博士协商进行。通过这项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：亚临床微栓子在临床上是否相关？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、更好的治疗方法和干预技术的可能改进来优化我们的卒中预防策略至关重要。通过减少与血管相关的痴呆，减少潜在的微栓子相关的认知障碍也将对未来的公共健康产生重大影响。正在进行的关于CAS治疗指南的辩论增加了这项研究的紧迫性。该提案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衡量标准。不管微栓子对认知的影响如何，危险因素分层是提高颈动脉介入治疗质量的独特机会。

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.