Blood Flow and Cognition in Asymptomatic Carotid Artery Disease

无症状颈动脉疾病的血流和认知

• 批准号: 8305855
• 负责人: RONALD M LAZAR
• 金额: $ 41.11万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8305855
• 关键词: Address; Affect; Age; Algorithms; Apolipoprotein E; Applications Grants; Blood Pressure; Blood Vessels; Blood flow; Brain; Breathing; Carbon Dioxide; Caregivers; Carotid Arteries; Carotid Artery Diseases; Carotid Stenosis; Cells; Cerebrovascular Circulation; Cerebrum; Chronic; Clinical; Clinical Trials; Cognition; Cognitive; Coupling; Dementia; Diabetes Mellitus; Diagnostic; Disease; Failure; Family; Functional disorder; General Population; Genotype; Goals; Homeostasis; Image; Impaired cognition; Impairment; Individual; Infarction; Lead; Life; Link; Magnetic Resonance Imaging; Measures; Mediating; Medical; Mental Depression; Metabolic; Metabolic syndrome; Neurocognitive; Neurologic; Neurologic Dysfunctions; Neurons; Patient Care; Patients; Physiological; Physiology; Population; Prevention; Progressive Disease; Public Health; Quality of life; Recurrence; Regulation; Reporting; Rest; Risk Factors; Spin Labels; Stenosis; Stroke; Testing; Time; Tissues; Vasomotor; aging population; arteriole; blood pressure regulation; clinical practice; cognitive function; follow-up; hemodynamics; improved; interest; meetings; response; tool; trend

DESCRIPTION (provided by applicant): Converging evidence from our lab and others suggests that an independent correlation exists between cerebral hemodynamic failure and cognitive impairment in patients with high-grade carotid artery stenosis. The implication of such a relationship is that cognitive dysfunction due to hemodynamic failure appears to represent one of the few examples of treatable cognitive impairment, yet current management algorithms for carotid disease focus only on the prevention of recurrent stroke. In addition, improved medical therapy for patients with carotid artery stenosis such as the widespread use of statins and better blood pressure control has led a clinical practice trend toward medical management for patients with asymptomatic ICA stenosis. The demonstration that some patients with carotid artery stenosis are living with reversible cognitive impairment would have compelling public-health impact, however, with 124,000 individuals over age 60 currently harboring high-grade carotid stenosis in the US alone. It has only been over the last few years -- as the tools to measure cerebral hemodynamic function have become increasingly sophisticated and the cognitive profile of patients with vascular cognitive impairment (VCI) has become clearer -- that we are presented with the opportunity to advance our understanding of the physiological link between hemodynamic failure and cognitive dysfunction. Such proof of concept (followed by a clinical trial) is necessary for any shift in clinical practice to be considered. We plan to study 158 patients over a 5-year period to determine the spectrum of cognitive dysfunction in those with e80%, both at baseline and over a 2-year follow up period. We will investigate the correlation of cognitive dysfunction with 4 hemodynamic factors: cerebral blood flow (CBF) as measured quantitatively with arterial spin labeling (ASL) MRI, cerebral vasomotor reactivity (VMR) and dynamic cerebral autoregulation (DCA) as measured by transcranial Doppler, and neurovascular coupling measured quantitatively with functional ASL imaging of the hemodynamic response to task-related neuronal activity. CBF and all 3 types of blood flow regulation have been reported to be impaired in the setting of carotid artery disease, and all have been associated with neurological dysfunction. It is as yet unknown, however, whether these hemodynamic variables mediate cognitive impairment in the setting of carotid artery disease. Successful elucidation of these hemodynamic mechanisms will contribute substantially to our knowledge of vascular cognitive impairment (VCI), and potentially lead to a significant shift in treatment algorithms for carotid artery stenosis. PUBLIC HEALTH RELEVANCE: Cognitive impairment is of increasing interest in our aging population. Causes are incompletely understood. It is hypothesized that low blood flow to the brain due to carotid artery disease contributes to cognitive impairment. Demonstrating the link between cerebral blood flow dysregulation and cognitive impairment could lead to a major shift in the treatment algorithms of carotid artery disease affecting tens of thousands of individuals in the US each year.

描述（由申请人提供）：我们实验室和其他人的融合证据表明，高级颈动脉狭窄患者的脑血液动力学衰竭与认知障碍之间存在独立的相关性。这种关系的含义是，由于血液动力学衰竭引起的认知功能障碍似乎代表了少数可治疗认知障碍的例子之一，但目前对颈动脉疾病的管理算法仅关注预防复发性中风。此外，改善了颈动脉狭窄患者的药物疗法，例如汀类药物的广泛使用和更好的血压控制，已导致无症状ICA狭窄患者的医疗管理临床实践趋势。一些颈动脉狭窄患者患有可逆的认知障碍的证明将产生引人注目的公共卫生影响，但是，仅在美国，目前有124,000名60岁以上的人就有高级颈动脉狭窄。它仅在过去几年中 - 随着测量脑血液动力学功能的工具越来越复杂，血管认知障碍（VCI）患者的认知能力变得更加清晰 - 我们有机会促进我们对血液动力衰竭和认知能力失调之间生理联系的理解的机会。对于要考虑临床实践的任何转变，必须进行这种概念证明（然后进行临床试验）。我们计划在5年期间研究158例患者，以确定E80％的认知功能障碍的频谱，无论是在基线时还是在2年的随访期内。我们将研究认知功能障碍与4种血液动力学因素的相关性：大脑血流（CBF），如动脉自旋标记（ASL）MRI，脑血管锻炼（ASL）MRI，大脑血管运动反应性（VMR）和动态自动调节（DCA）的定量测​​量（DCA），并通过转型量和NEURCRAINTIRITION，以及NEURERITER cOU，并通过跨量表进行了测量。对与任务相关的神经元活性的血液动力学反应的ASL成像。据报道，CBF和所有3种类型的血流调节在颈动脉疾病的情况下受到损害，并且都与神经功能障碍有关。然而，这些血液动力学变量在颈动脉疾病的情况下是否介导认知障碍是尚不清楚的。成功阐明这些血液动力学机制将有助于我们对血管认知障碍（VCI）的了解，并有可能导致颈动脉狭窄的治疗算法发生显着转移。 公共卫生相关性：认知障碍在我们的老龄化人群中越来越兴趣。原因是不完全理解的。假设由于颈动脉疾病而流向大脑的血液流量低，导致认知障碍。证明脑血流失调与认知障碍之间的联系可能导致颈动脉疾病的治疗算法发生重大变化，影响了成千上万个个体 美国每年。