Study of Carotid Occlusion and Neurocognition (RECON)

描述（由申请人提供）：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——预防卒中复发——然而越来越多的证据表明，认知功能受到颈动脉疾病和血流动力学损伤的影响。我们提出一项新资助的辅助研究，ninds赞助的颈动脉闭塞手术研究（COSS），以验证认知结果与脑灌注不足治疗相关且重要的假设。COSS试验的目的是验证EC-IC旁路治疗可以降低最近症状性颈内动脉闭塞和II期血流动力学衰竭患者2年卒中复发率40%的假设，这是通过正电子发射断层扫描（PET）上氧气提取分数（OEF）的增加来测量的。我们建议在随机COSS患者的认知状态评估中使用全脑和半球特异性神经认知测试，该测试需要不到一个小时的时间。我们的具体目的是确定有症状的，单侧颈动脉闭塞和PET证据的II期脑血流动力学衰竭患者，如果没有达到COSS终点（同侧卒中），在EC-IC搭桥后3个月和2年的认知功能是否比单独接受最佳药物治疗的相同组患者更好。我们提出这一建议的动力来自于初步数据，在这些数据中，我们证明了在颈动脉测试闭塞的情况下，脑血流量（CBF）与较高的皮质功能之间的定量关系。我们和其他人在病例系列研究中进一步证明了接受动脉内膜切除术或颅外-颅内（EC-IC）旁路治疗的颈动脉狭窄或闭塞患者的认知改善。在我们提出的研究中，大约294名患者将在随机化时进行神经认知测试；然后在EC-IC搭桥后30天、3个月和2年或在COSS医疗组的等效时间点。所有患者将在3个月后进行随访PET扫描，以确定实际OEF状态。调整由于COSS试验终点导致的预期退出，我们将有80%的能力在0.05的alpha水平上检测到0.5 SD的认知评分差异。认知评分与COSS残疾和生活质量措施的相关性将被建立，以建立认知变化的临床相关性。如果再灌注手术可以改善认知能力，那么COSS试验将会受益，除此之外，本研究的积极发现可以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.