Study of Carotid Occlusion and Neurocognition (RECON)

描述(申请人提供)：治疗颈动脉疾病的临床试验几乎完全集中在一个单一的结果上--防止中风复发--然而，越来越多的证据表明，认知功能受到颈动脉疾病和血液动力学损害的影响。我们建议对新资助的NINDS赞助的颈动脉闭塞手术研究(COSS)进行一项辅助研究，以检验认知结果在脑低灌注症治疗中相关和重要的测量这一假设。COSS试验旨在验证这样一种假设，即EC-IC搭桥术可以将最近出现症状的颈内动脉闭塞和II期血流动力学衰竭患者在两年内再次中风的几率降低40%，这是通过正电子发射断层扫描(PET)上增加的氧提取分数(OEF)来衡量的。我们建议使用一组不到一小时的电池，使用全球和半球特有的神经认知测试来评估随机分组COSS患者的认知状态。我们的具体目标是确定有症状的单侧颈动脉闭塞且PET证据显示II期脑血流动力学衰竭且未达到COSS终点(同侧中风)的患者，与接受最佳药物治疗的相同组患者相比，EC-IC搭桥术后3个月和2年是否会有更好的认知功能。我们建议的动机来自初步数据，在这些数据中，我们证明了在颈动脉测试性闭塞设置中，脑血流量(CBF)和较高的皮质功能之间的定量关系。我们和其他人在颈动脉狭窄或闭塞患者接受动脉内膜切除术或颅外-颅内(EC-IC)搭桥术的病例系列研究中进一步证明了认知功能的改善。在我们建议的研究中，大约294名患者将在随机时间进行神经认知测试；然后在EC-IC搭桥后30天、3个月和2年后或在COSS医疗组的同等时间点进行神经认知测试。所有患者将在3个月后接受随访PET扫描，以确定实际的OEF状态。对COSS试验中由于终点而导致的预期退学进行调整后，我们将有80%的能力在阿尔法水平0.05的情况下检测认知分数的0.5SD差异。认知得分与COSS残疾和生活质量测量的相关性将被用来建立认知变化的临床相关性。如果再灌注手术被证明可以改善认知，除了对COSS试验的好处外，这项研究的积极发现可能为在其他颈动脉疾病治疗试验中使用类似的认知措施铺平道路。

DESCRIPTION (provided by applicant): Clinical trials for the treatment of carotid artery disease have focused almost exclusively on a single outcome --prevention of recurrent stroke -- yet accumulating evidence suggests that cognitive function is affected by carotid artery disease and hemodynamic impairment. We propose an ancillary study to the newly-funded, NINDS-sponsored Carotid Occlusion Surgery Study (COSS) to test the hypothesis that cognitive outcomes are relevant and important to measure in the treatment of cerebral hypoperfusion. The COSS trial is designed to test the hypothesis that EC-IC bypass can reduce by 40% the rate of recurrent stroke at 2 years in patients with recently symptomatic internal carotid artery occlusion and Stage II hemodynamic failure as measured by increased oxygen extraction fraction (OEF) on positron emission tomography (PET). We propose to evaluate the cognitive status in randomized COSS patients using global and hemisphere-specific neurocognitive tests in a battery that takes less than an hour to administer. Our specific aim is to determine whether patients who have symptomatic, unilateral carotid artery occlusion and PET evidence of stage II cerebral hemodynamic failure who do not reach a COSS endpoint (ipsilateral stroke) will have better cognitive function 3 months and 2 years following EC-IC bypass compared with an identical group of patients treated with best medical therapy alone. The impetus for our proposal comes from preliminary data in which we demonstrated a quantitative relationship between cerebral blood flow (CBF) and higher cortical function in the setting of carotid artery test occlusion. We and others have further demonstrated cognitive improvement in case series studies of patients with carotid stenosis or occlusion treated with endarterectomy or extracranial-intracranial (EC-IC) bypass. In our proposed study approximately 294 patients will have neurocognitive testing at time of randomization; then 30 days, 3 months, and 2 years after EC-IC bypass or the equivalent time point in the COSS medical arm. All patients will undergo a follow-up PET scan at 3 months to determine actual OEF status. Adjusting for anticipated drop-out due to end-points in the COSS trial, we will have 80% power to detect a 0.5 SD difference in cognitive scores at an alpha level of 0.05. Correlation of cognitive scores with COSS disability and quality of life measures will be made to establish the clinical relevance of change in cognition. In addition to the benefit to the COSS trial if reperfusion surgery can be shown to be improve cognition, positive findings in this study could pave the way for the use of similar cognitive measures in other carotid disease treatment trials.