Neuroimaging Correlates of Memory Decline Following Carotid Interventions

描述(申请人提供)：记忆力衰退是阿尔茨海默病的最早症状之一，人们越来越意识到血管疾病会加速这种痴呆症的衰退过程。虽然颈动脉内膜剥脱术(CEA)和颈动脉支架植入术(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，接受这些手术的老年人中约有四分之一经历了认知能力下降。我们最近资助的NIH项目是研究记忆下降，目标是将认知变化与颈动脉干预期间或之后发生的微栓子病变联系起来(R01 NS070308)。R01的最终目标是确定手术程序和患者因素中增加认知能力下降风险的方面，以便能够预防。该项目的研究导致了目前的提议。使用一种新的神经成像方法，我们对手术后磁共振成像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。这张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，在术后记忆力下降的患者中，这些易受微栓子影响的区域的白质(WM)密度降低。根据我们的初步评估，我们认为脑血流量(CBF)减少、脑WM完整性降低和操作相关的微栓塞术密切相关。我们提出了一个新的概念，即一个单一的模型，综合了所有三个与程序相关的认知恶化的危险因素。我们假设HRZ的脑白质异常和脑血流减少与微栓子的频率和认知效应有关。在这项建议中，我们将增加弥散张量成像(DTI)来评估白质完整性，并增加动脉自旋标记(ASL)来评估脑血流。我们将首先确定HRZ中白质异常对颈动脉介入相关微栓子和认知改变的影响；我们还将检查CBF对操作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的分析工具，我们希望确定有可能出现与手术相关的认知恶化的患者亚群。这一建议反映了我们为改善干预结果所做的持续努力。这项建议是对我们NIH R01的补充，将有助于更好地了解颈动脉血运重建后认知恶化的潜在原因，并可能有助于通过个性化患者护理改善认知结果。 公共卫生相关性：颈动脉血运重建可以显著降低中风的风险，但在25%的患者中，它与认知能力下降有关。神经成像技术表征了白质的完整性和局部低灌注量，有可能提供敏感的脑结构指标，这些指标可能与血运重建过程后记忆下降有关。这项建议通过增加扩散张量成像和动脉自旋标记来增强现有的R01，这是白质完整性和脑血流的敏感指标。一般的假设是，尖端的MRI测量方法可以帮助预测患者出现与程序相关的记忆力下降的风险，因此可以应用个性化的患者护理。

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.