Asymptomatic Carotid Stenosis: Cognitive Function and Plaque Correlates - 2

血管性认知功能障碍是一种潜在的疾病，由累积的缺血性损伤引起的， 个脑袋我们的VA Merit资助的无症状颈动脉狭窄和认知功能（ACCOF）发现， 在颈动脉狭窄的情况下，行为改变可以在没有身体表现的情况下发生。 中风另外，无症状颈动脉狭窄患者的认知能力比对照组差。 此外，大约40%的狭窄患者在基线时有脑血流动力学损害; 血流动力学损害与认知障碍相关。并不是所有的颈动脉狭窄患者 减少脑灌注。斑块的几何形状（狭窄程度、斑块的长度和形状） 正如我们已经证明的，大脑内跨Willis环的侧支化程度， 脑灌注 这些发现意味着一部分颈动脉狭窄患者存在血流动力学异常， 通过去除狭窄而逆转血液动力学异常可 改善相关的认知障碍。因此，颈动脉狭窄的治疗可能需要 扩大到包括认知相关生活质量（QoL）的保护。一些示威者 患有颈动脉狭窄的患者患有可逆性认知障碍， 影响颈动脉狭窄影响2-12%的人。全国有2300万退伍军人， 100万（4.3%）将有狭窄。ACCOF显示，这些患者存在认知障碍的风险 如果进行干预，这可能是可逆的 我们提出了一项纵向对照观察性研究，评估颈动脉血运重建术是否 改善脑血流动力学受损患者的认知功能障碍。概念验证（随后 通过临床试验）在考虑临床实践的转变之前是必要的。如果认知能力下降可以 在这些患者中逆转，我们将建立一个新的颈动脉血运重建适应症， 预防中风的方法。我们将入组138例无症状高度（≥70%）颈动脉狭窄患者 接受颈动脉内膜切除术预计约40%（n=55例患者）的患者 基线时脑灌注受损（研究组）;其余60%（n=83）将有颈动脉 狭窄，但灌注不会受损（对照组）。 我们的主要目的是确定颈动脉血运重建术是否能改善1年后的认知能力。 基线时脑血流动力学受损的患者。我们假设， 接受颈动脉内膜切除术的无症状颈动脉狭窄患者， 基线时脑灌注受损的患者与基线灌注正常的患者。我们 次要目标1将确定脑血流动力学损害是否是压力下降的结果 穿过狭窄的颈动脉我们假设在所有入选的患者中，PWI-TTP的程度 基线延迟将与颈动脉狭窄处的压降程度相关。压降将 通过基于颈动脉管腔的3D成像的患者特异性计算流体动力学建模来测量 Willis环的几何形状、流量测量和循环分析。第二目标2将 确定血运重建后的认知改善是否是脑功能改善的结果， 血流动力学我们假设在基线时PWI-TTP延迟的患者中， 再血管化后认知的改善将与压降的改善相关。 次要目标3将确定两组之间认知结果的差异是否影响 生活质量我们假设血运重建后1年，患者的生活质量将得到更大的改善 基线脑灌注受损的患者与无损伤的患者相比。

Vascular cognitive impairment is an insidious disease resulting from accumulated ischemic injury to the brain. Our VA Merit-funded Asymptomatic Carotid Stenosis and Cognitive Function (ACCOF) found that in the setting of carotid stenosis, alterations of behavior can occur in the absence of physical manifestations of stroke. Otherwise asymptomatic patients with carotid stenosis had worse cognitive performance than controls. In addition, approximately 40% of patients with stenosis had cerebral hemodynamic compromise at baseline; and hemodynamic compromise correlated with cognitive impairment. Not all patients with carotid stenosis have reduced cerebral perfusion. The geometry of the plaque (degree of stenosis, length and shape of the plaque) and, as we have demonstrated, the extent of intra-cerebral collateralization across the Circle of Willis, influence cerebral perfusion. The implication of these findings is that a subset of carotid stenosis patients has hemodynamic compromise, and that reversal of the hemodynamic abnormalities by removing the stenosis may ameliorate the associated cognitive impairment. Therefore, treatment for carotid stenosis might need to be broadened to include preservation of cognition-related Quality of Life (QoL). The demonstration that some patients with carotid stenosis are living with reversible cognitive impairment would have important public-health implications. Carotid stenosis affects 2-12% of people. With 23 million Veterans in the country, approximately 1 million (4.3%) will have a stenosis. ACCOF shows that these patients are at risk for cognitive impairment which, with intervention, might be reversible. We propose a longitudinal controlled observational study that assesses whether carotid revascularization improves cognitive dysfunction in patients with cerebral hemodynamic compromise. Proof of concept (followed by a clinical trial) is necessary before a shift in clinical practice is considered. If cognitive decline can be reversed in these patients, we will have established a new indication for carotid revascularization independent of stroke prevention. We will enroll 138 patients with asymptomatic high-grade (≥70%) carotid stenosis undergoing planned carotid endarterectomy. Approximately 40% (n=55 patients) of patients are anticipated to have compromised cerebral perfusion at baseline (study group); the remaining 60% (n=83) will have carotid stenosis but will not have compromised perfusion (control group). Our Primary Aim will determine if carotid revascularization improves cognitive performance at 1 year in patients with cerebral hemodynamic compromise at baseline. We hypothesize that among patients with asymptomatic carotid stenosis undergoing carotid endarterectomy, cognitive performance will improve more in those with impaired cerebral perfusion at baseline versus those with normal baseline perfusion. Our Secondary Aim 1 will determine whether cerebral hemodynamic compromise is the result of pressure drop across the carotid artery stenosis. We hypothesize that among all patients enrolled, the degree of PWI-TTP delay at baseline will correlate with the degree of pressure drop across the carotid stenosis. Pressure drop will be measured by patient-specific computational fluid dynamic modeling based on 3D imaging of carotid luminal geometry, flow measurements, and analysis of the circulation in the Circle of Willis. Secondary Aim 2 will determine whether cognitive improvement after revascularization is the result of improved cerebral hemodynamics. We hypothesize that among patients with delayed PWI-TTP at baseline, the degree of improvement in cognition after revascularization will correlate with the improvement in pressure drop. Secondary Aim 3 will determine whether differences in cognitive outcome between the two groups impact quality of life. We hypothesize that 1 year after revascularization, quality of life will improve more in patients with impaired baseline cerebral perfusion versus those without impairment.