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

尽管进行了数十年的研究，但对于如何有效预防术后谵妄或术后 认知功能障碍;然而，关于血脑屏障（BBB）在健康和 疾病表明，增加的渗透性（BBB功能障碍）可能与发展有关， 术后谵妄（POD）和术后认知功能障碍（POCD）。多达一半的老年人 据报道，65岁以上的手术患者中有5 - 20%患有POD和POCD;目前， 有效预防或治疗，两者都与生活质量和生存率下降有关， 还有很多其他的负面结果。我们的长期目标是提高对手术应激对 老化的大脑，最终导致有效的策略，以提高手术的认知安全性。的目标 这项研究是为了调查一种创新的脑成像技术，水交换指数MRI， 在一项对老年人的纵向研究中， 接受重大择期非心脏手术的成年人。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 认知能力下降我们将通过实现以下具体目标来测试这一假设：1）评估 BBB通透性与POD发生率之间的相关性; 2）评估BBB通透性与POD发生率之间的相关性。 渗透性和POCD的发生率;和3）确定内皮损伤的标志物的变化， 外周血炎症可预测POD和POCD。这种方法是创新的，因为它采用了 非侵入性技术，以精确测量BBB渗透性，并查明脑中的区域， 发生。本文的研究具有重要的意义，为今后的发展奠定了基础 干预措施，以提高老年人重大择期手术的认知安全性。识别BBB 功能障碍在确定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.