Blood-Brain Barrier Disruption as a Biomarker for Perioperative Neurocognitive Disorder:Cognitive Recovery after Elective Surgery

血脑屏障破坏作为围手术期神经认知障碍的生物标志物：择期手术后的认知恢复

• 批准号: 10358525
• 负责人: lori A daiello
• 金额: $ 71.71万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10358525
• 关键词: Acute; Albumins; Animal Model; Area; Attention; Benign; Biological Markers; Blood; Blood - brain barrier anatomy; Blood Circulation; Brain; Brain imaging; Cardiac; Cerebrovascular Disorders; Chronic Disease; Cognition Disorders; Cognitive; Day Surgery; Delirium; Development; Diabetes Mellitus; Disease; Elderly; Endothelium; Event; Failure; Functional disorder; Future; Genetic Risk; Goals; Growth; Health; Hospitalization; Image; Imaging Techniques; Impaired cognition; Impairment; Incidence; Inflammation; Inflammatory Response; Injury; Inpatients; Intervention; Knowledge; Learning; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Memory; Modeling; Neurons; Nursing Homes; Operative Surgical Procedures; Outcome; Patients; Perioperative; Peripheral; Permeability; Physical Function; Population; Postoperative Period; Predisposition; Prevention strategy; Preventive treatment; Procedures; Public Health; Quality of life; Radioactive; Reporting; Research; Retirement; Risk; Risk Factors; Role; Safety; Serum; Stress; Structure; Technology; Testing; Toxin; United States; Water; Work; aging brain; aging population; blood-brain barrier disruption; blood-brain barrier permeabilization; cognitive function; cognitive recovery; cost; dementia risk; endothelial dysfunction; experience; follow-up; improved; indexing; inflammatory marker; innovation; insight; neurocognitive disorder; neuroimaging; neuroinflammation; neurovascular; older patient; peripheral blood; post-operative cognitive dysfunction; postoperative delirium; premature; prevent; prognostic; readmission risk; treatment strategy

Despite decades of research, little is known about how to effectively prevent postoperative delirium or postoperative cognitive dysfunction; however, emerging perspectives on the role of the blood-brain barrier (BBB) in health and disease suggest that increased permeability (BBB dysfunction) may be associated with the development of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). Up to half of all older adults develop POD, and POCD is reported in 5-20% of surgical patients over 65 years; at present, neither condition can be effectively prevented nor treated and both are associated with decreased quality of life and survival, as well as numerous other negative outcomes. Our long-term goal is to advance knowledge of the effects of surgical stress on the aging brain, ultimately leading to effective strategies to improve the cognitive safety of surgery. The objective of this research is to investigate the extent to which an innovative brain imaging technique, water exchange index MRI (WEI-MRI) evidence of BBB dysfunction predicts the incidence of POD and POCD, in a longitudinal study of older adults undergoing major elective non-cardiac surgeries. Our central hypothesis is that in the aging brain, BBB dysfunction is a biomarker for brain vulnerability that predicts increased risk for POD, POCD, and progressive cognitive decline. We will test this hypothesis by accomplishing the following specific aims: 1) Evaluate associations between BBB permeability and the incidence of POD; 2) Evaluate associations between BBB permeability and the incidence of POCD; and 3) Identify changes in markers of endothelial injury and inflammation in peripheral blood that predict POD and POCD. This approach is innovative because it employs a noninvasive technology to precisely measure BBB permeability and pinpoint the area(s) of the brain in which it occurs. The proposed research is significant in that it will lay essential groundwork for development of future interventions to improve the cognitive safety of major elective surgeries in the aging population. Recognition of BBB dysfunction may be of critical prognostic importance in determining brain susceptibility to surgical stress.

尽管进行了数十年的研究，但对于如何有效预防术后del妄或术后的知识知之甚少 认知功能障碍；但是，关于血脑屏障（BBB）在健康和 疾病表明，渗透率提高（BBB功能障碍）可能与 术后del妄（POD）和术后认知功能障碍（POCD）。最多一半的老年人发展 在65年内，有5-20％的手术患者中有5-20％的POD和POCD；目前，两种情况都不能 有效预防或治疗，都与生活质量和生存质量降低有关，以及 许多其他负面结果。我们的长期目标是促进对手术压力的影响的了解 衰老的大脑，最终导致了改善手术认知安全性的有效策略。目的 这项研究是为了研究创新的大脑成像技术，水交换指数MRI的程度 （WEI-MRI）BBB功能障碍的证据预测了POD和POCD的发生率，在纵向研究中 成人接受了大规模的选修非心脏手术。我们的中心假设是在衰老的大脑中 功能障碍是大脑脆弱性的生物标志物，可预测POD，POCD和进行性疾病的风险增加 认知能力下降。我们将通过实现以下特定目的来检验这一假设：1）评估 BBB渗透性与POD发生率之间的关联； 2）评估BBB之间的关联 渗透性和POCD的发生率； 3）确定内皮损伤标记的变化和 预测POD和POCD的外周血中的炎症。这种方法是创新的，因为它采用了 精确测量BBB渗透性并查明其大脑的面积的无创技术 发生。拟议的研究很重要，因为它将为发展未来的发展奠定基础 改善老龄化人口的主要选修手术的认知安全性的干预措施。识别BBB 功能障碍对于确定大脑对手术应激的敏感性可能至关重要。