Asymptomatic Carotid Stenosis: Cognitive Function and Plaque Correlates - 2

无症状颈动脉狭窄：认知功能和斑块相关 - 2

• 批准号: 9932930
• 负责人: Brajesh K Lal
• 金额: --
• 依托单位: BALTIMORE VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9932930
• 关键词: Affect; Age; Aging; Algorithms; Attention; Behavior; Blood Circulation; Brain; Carotid Artery Diseases; Carotid Endarterectomy; Carotid Stenosis; Cerebral Infarction; Cerebrovascular Circulation; Cerebrum; Circle of Willis; Clinical Trials; Cognition; Cognitive; Control Groups; Country; Data; Disease; Drops; Education; Enrollment; Evaluation; Funding; Geometry; Health Expenditures; Impaired cognition; Impairment; Intervention; Lead; Learning; Length; Liquid substance; Measurement; Measures; Memory; Modeling; Motor; Observational Study; Outcome; Patients; Perfusion; Perfusion Weighted MRI; Prevalence; Public Health; Quality of life; Race; Reporting; Risk; Shapes; Short-Term Memory; Stenosis; Stroke; Stroke prevention; Testing; Three-Dimensional Imaging; Time; Vascular Cognitive Impairment; Veterans; White Matter Hyperintensity; base; cerebral hemodynamics; cerebrovascular; clinical practice; cognitive change; cognitive function; cognitive performance; executive function; hemodynamics; improved; indexing; interest; ischemic injury; military veteran; preservation; pressure; primary endpoint; processing speed; sex; vascular risk factor

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.

血管性认知功能障碍是一种由脑缺血累积性损伤引起的潜伏性疾病 大脑。我们由退伍军人事务部资助的无症状颈动脉狭窄和认知功能(ACCOF)发现，在 颈动脉狭窄的背景下，在没有生理表现的情况下，可以发生行为改变 卒中。此外，无症状的颈动脉狭窄患者的认知表现比对照组更差。 此外，约40%的狭窄患者在基线时有脑血流动力学障碍； 血流动力学折衷与认知损害相关。并不是所有的颈动脉狭窄患者 大脑灌注量减少。斑块的几何形状(狭窄程度、斑块长度和形状) 正如我们已经证明的，威利斯环脑内侧支循环的影响程度 脑血流灌注。 这些发现的含义是颈动脉狭窄患者中的一部分具有血流动力学。 且通过移除狭窄来逆转血流动力学异常可以 改善相关的认知障碍。因此，颈动脉狭窄的治疗可能需要 扩大到包括与认知相关的生活质量(QOL)的保存。证明了一些人 颈动脉狭窄患者患有可逆性认知障碍将有重要的公共健康 这意味着什么。2-12%的人会受到颈动脉狭窄的影响。这个国家有2300万退伍军人，大约 100万人(4.3%)将出现狭窄。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 改善脑血流动力学受损患者的认知功能障碍。概念验证(遵循 临床试验)是必要的，然后才考虑临床实践的转变。如果认知能力下降可以 在这些患者中，我们将建立一个独立于颈动脉血运重建的新指征 预防中风。我们将招募138名无症状的高度颈动脉狭窄(≥70%)患者 正在接受计划中的颈动脉内膜切除术。大约40%(n=55名患者)的患者预计会 脑血流灌注在基线水平受损(研究组)；其余60%(n=83)将有颈动脉 狭窄但不影响血流灌注(对照组)。 我们的主要目标将确定颈动脉血运重建术是否能在1岁时改善认知能力 患者的脑血流动力学在基线水平上有所下降。我们假设，在患有 接受颈动脉内膜切除术的无症状颈动脉狭窄患者，认知能力将得到更大改善 基线脑血流灌注受损者与基线脑血流灌注正常者比较。我们的 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 穿过颈动脉狭窄。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的压力下降程度相关。压降将 通过基于颈动脉腔三维成像的特定患者计算流体动力学模型进行测量 威利斯环流的几何、流量测量和分析。次要目标2将 确定血运重建后的认知改善是否是大脑功能改善的结果 血流动力学。我们假设在基线时PWI-TTP延迟的患者中， 血运重建后认知功能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会影响 生活质量。我们假设在血运重建1年后，患者的生活质量将得到更多的改善。 基线脑血流灌注受损者与无受损者比较。