Neuroimaging Correlates of Memory Decline Following Carotid Interventions

描述（由申请人提供）：记忆衰退是阿尔茨海默病的早期症状之一，越来越多的人意识到血管疾病可以加速这种痴呆症的衰退过程。尽管颈动脉内膜切除术（CEA）和颈动脉支架置入术（CAS）都是预防严重颈动脉闭塞性疾病患者中风的有效治疗方法，但最近的研究表明，大约四分之一接受这些手术的老年人会出现认知能力下降。我们最近资助的NIH项目是研究记忆衰退，目的是将认知变化与颈动脉干预期间或之后发生的微栓塞病变联系起来（R01 NS070308）。R01的最终目标是确定手术过程的各个方面和患者因素会增加认知能力下降的风险，这样就可以预防了。那个项目的研究导致了现在的提案。使用一种新的神经成像方法，我们对术后mri记录的微栓子进行了体积分析，并生成了微栓子的数字地图。该图与血流动力学危险区（HRZ）的大致位置非常相似。我们还发现，在手术后记忆衰退的患者中，这些易发生微栓子的区域的白质（WM）密度降低。根据我们的初步评估，我们认为脑血流量减少（CBF）、脑WM完整性降低和手术相关的微栓塞密切相关。我们提出了一个新的概念，一个单一的模型整合所有三个风险因素的程序相关的认知退化。我们假设脑白质异常和脑血流量减少有助于微栓子的频率和认知影响。在本提案中，我们将增加扩散张量成像（DTI）来评估白质完整性和动脉自旋标记（ASL）来评估脑血流。我们将首先确定HRZ白质异常对颈动脉介入相关微栓塞和认知改变的影响；我们还将研究脑血流对手术相关微栓子和认知改变的影响。通过先进的神经成像技术和新颖的分析工具，我们希望识别出有手术相关认知退化风险的患者子集。这一建议反映了我们为改善干预结果所做的持续努力。补充我们的NIH R01，该建议将有助于更好地了解颈动脉血运重建后认知恶化的潜在病因，并可能通过个体化患者护理来帮助改善认知结果。

DESCRIPTION (provided by applicant): Memory decline is one of the earliest symptoms of Alzheimer's disease and there is a growing awareness that vascular disease can accelerate the course of decline for this dementia. Whereas both carotid endarterectomy (CEA) and carotid stenting (CAS) are effective treatments for stroke prevention in patients with severe carotid occlusive diseases, recent studies suggest that approximately a quarter of elderly adults undergoing these procedures experience cognitive decline. Our recently funded NIH project is to study memory decline with the goal of relating cognitive changes to microembolic lesions that occur during or after carotid intervention (R01 NS070308). The ultimate goal of that R01 is to identify the aspects of the surgical procedures and patient factors that increase the risk of cognitive decline so that they can be prevented. The research from that project led to the current proposal. Using a novel neuroimaging approach, we performed volumetric analysis of microemboli that were documented on post-procedural MRIs and generated a digital map of microemboli. This map remarkably resembled the general location of hemodynamic risk zone (HRZ). We have also shown decreased white matter (WM) density in these areas vulnerable to microemboli among the patients who had post-procedural memory decline. Based on our preliminary evaluations, we believe that reduced cerebral blood flow (CBF), decreased brain WM integrity, and procedure-related microembolization are intimately related. We propose a novel concept of a single model integrating all three risk factors for procedure-related cognitive deterioration. We hypothesize that brain white matter abnormality and cerebral blood flow reduction in HRZ contribute to the frequency and cognitive effects of microemboli. In this proposal, we will add diffusion tensor imaging (DTI) to evaluate white matter integrity and arterial spin labeling (ASL) to evaluate cerebral blood flow. We will first determine the effects o white matter abnormality in HRZ on carotid interventions-associated microemboli and cognitive changes; we will also examine the effects of CBF on procedure-associated microemboli and cognitive change. Through advanced neuroimaging techniques and novel analytical tools, we hope to identify a subset of patients at risk for procedure-associated cognitive deterioration. Thi proposal reflects our continuous efforts to improve interventional outcomes. Complementary to our NIH R01, this proposal will help to better understand the underlying etiology of cognitive deterioration following carotid revascularization and will potentially help to improve cognitive outcome by individualizing patient care. PUBLIC HEALTH RELEVANCE: Carotid revascularization can significantly reduce the risk of stroke, but it has been associated with cognitive decline in 25% of the patients. Neuroimaging techniques that characterize white matter integrity and regional hypoperfusion have the potential to provide sensitive brain structure indicators that may be associated with memory decline following revascularization procedures. This proposal enhances an existing R01 by adding diffusion tensor imaging and arterial spin labeling, sensitive measures for white matter integrity and cerebral blood flow. The general hypothesis is that cutting-edge MRI measures can help to predict patients at risk for procedure-associated memory decline, and therefore individualized patient care can be applied.