Study of Carotid Occlusion and Neurocognition (RECON)

描述（由申请人提供）：颈动脉疾病治疗的临床试验几乎完全集中在一个单一的结果-预防复发性卒中-但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害的影响。我们提出了一项新资助的NINDS赞助的颈动脉闭塞手术研究（COSS）的辅助研究，以检验认知结果在脑灌注不足治疗中的相关性和重要性。COSS试验旨在检验以下假设：EC-IC旁路术可将近期有症状的颈内动脉闭塞和II期血流动力学衰竭患者2年时的复发性卒中率降低40%（通过正电子发射断层扫描（PET）测得的氧摄取分数（OEF）增加进行测量）。我们建议使用整体和半球特异性神经认知测试评估随机COSS患者的认知状态，测试时间不到一小时。我们的具体目的是确定有症状的单侧颈动脉闭塞和PET证据显示II期脑血流动力学衰竭但未达到COSS终点（同侧卒中）的患者在EC-IC旁路移植术后3个月和2年是否比单独接受最佳药物治疗的同一组患者具有更好的认知功能。我们的建议的动力来自于初步数据，其中我们证明了在颈动脉测试闭塞的设置中，脑血流量（CBF）和更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）搭桥术治疗的病例系列研究中进一步证明了认知改善。在我们拟定的研究中，大约294例患者将在随机化时进行神经认知测试;然后在EC-IC旁路术后30天、3个月和2年或COSS医疗组的等效时间点进行神经认知测试。所有患者将在3个月时进行随访PET扫描，以确定实际OEF状态。调整COSS试验中因终点而导致的预期脱落，我们将有80%的把握度在α水平为0.05时检测到认知评分的0.5 SD差异。将进行认知评分与COSS残疾和生活质量测量的相关性，以确定认知变化的临床相关性。如果再灌注手术可以改善认知，除了COSS试验的益处外，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测量铺平道路。

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.