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

尽管进行了几十年的研究，但人们对如何有效预防术后精神错乱知之甚少。 然而，关于血脑屏障(BBB)在健康和健康中的作用的新观点 疾病提示通透性增加(血脑屏障功能障碍)可能与 术后精神障碍(POD)和术后认知功能障碍(POCD)。多达一半的老年人会患上 据报道，65岁以上的外科患者中有5%-20%患有POD和POCD；目前，这两种情况都不能 有效地预防或治疗，两者都与生活质量和生存质量下降以及 还有许多其他负面结果。我们的长期目标是促进对手术应激影响的了解 大脑老化，最终导致有效的策略，提高手术的认知安全性。的目标是 本研究旨在调查一种创新的脑成像技术--水交换指数磁共振成像技术在多大程度上 在一项老年人的纵向研究中，血脑屏障功能障碍的(WEI-MRI)证据预测POD和POCD的发生率 接受重大非心脏手术的成年人。我们的中心假设是，在老化的大脑中，血脑屏障 功能障碍是大脑脆弱性的生物标志物，预测POD、POCD和进展性疾病的风险增加 认知能力下降。我们将通过实现以下具体目标来验证这一假设：1)评估 血脑屏障通透性与POD发生率之间的关系；2)评估血脑屏障通透性与POD发生率之间的关系 通透性和POCD发生率；以及3)确定内皮损伤标志物的变化和 外周血中的炎症预示着POD和POCD。这种方法具有创新性，因为它采用了 无创技术精确测量血脑屏障通透性并精确定位脑内区域(S) 发生。所提出的研究具有重要意义，它将为未来的发展奠定必要的基础。 提高老龄人口大手术认知安全性的干预措施。对血脑屏障的再认识 功能障碍在确定大脑对手术应激的易感性方面可能具有关键的预后重要性。

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.