The INTUIT Study: Investigating Neuroinflammation Underlying Postoperative Cognitive Dysfunction
The INTUIT Study: Investigating Neuroinflammation Underlying Postoperative Cognitive Dysfunction
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DOI：
10.1111/jgs.15770
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发表时间：
2019-04-01
影响因子：
6.3
通讯作者：
Zani, Sabino
中科院分区：
文献类型：
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作者：
Berger, Miles;Oyeyemi, Deborah;Zani, Sabino
每年，在超过1600万接受麻醉/手术的美国老年人中，高达40%的人发生术后认知功能障碍（POCD）或谵妄。这些不同的综合征中的每一种都与生活质量下降、死亡率增加以及患阿尔茨海默病的风险可能增加有关。神经炎症被认为是谵妄和POCD的病理基础。本文描述的INTUIT研究将确定脑脊液（CSF）单核细胞趋化蛋白1（MCP-1）水平和单核细胞数量的术后增加与谵妄和/或POCD及其潜在脑连接变化相关的程度。设计观察性前瞻性队列研究。环境：杜克大学医学中心、杜克地区医院和杜克罗利医院。参与者：60岁或以上（N = 200）接受非心脏/非神经外科手术的患者。参与者将在手术前、手术后6周和1年接受认知测试。将在术后第1 - 5天进行谵妄筛查。在手术前、手术后24小时、6周和1年获得血液和CSF样品。通过酶联免疫吸附测定法测量CSF MCP-1水平，并通过流式细胞术评估CSF单核细胞。一半的患者还将接受术前和术后功能性磁共振成像扫描。32-将进行通道术中脑电图（EEG）记录，以确定神经炎症和/或术后认知恢复的术中EEG相关性。80名患者还将接受家庭睡眠呼吸暂停测试，以确定睡眠呼吸暂停严重程度，神经炎症和术后认知受损之间的关系。额外的评估将有助于评估谵妄，POCD和其他老年综合征之间的关系。结论INTUIT将采用跨学科的方法研究神经炎症在术后谵妄和认知功能障碍及其相关功能性脑连接变化中的作用，并可能为治疗和/或预防谵妄和POCD及其后遗症找到新的靶点。J Am Geriatr Soc 67：794-798，2019.
BACKGROUND/OBJECTIVES Every year, up to 40% of the more than 16 million older Americans who undergo anesthesia/surgery develop postoperative cognitive dysfunction (POCD) or delirium. Each of these distinct syndromes is associated with decreased quality of life, increased mortality, and a possible increased risk of Alzheimer's disease. One pathologic process hypothesized to underlie both delirium and POCD is neuroinflammation. The INTUIT study described here will determine the extent to which postoperative increases in cerebrospinal fluid (CSF) monocyte chemoattractant protein 1 (MCP-1) levels and monocyte numbers are associated with delirium and/or POCD and their underlying brain connectivity changes. DESIGN Observational prospective cohort. SETTING Duke University Medical Center, Duke Regional Hospital, and Duke Raleigh Hospital. PARTICIPANTS Patients 60 years of age or older (N = 200) undergoing noncardiac/nonneurologic surgery. MEASUREMENTS Participants will undergo cognitive testing before, 6 weeks, and 1 year after surgery. Delirium screening will be performed on postoperative days 1 to 5. Blood and CSF samples are obtained before surgery, and 24 hours, 6 weeks, and 1 year after surgery. CSF MCP-1 levels are measured by enzyme-linked immunosorbent assay, and CSF monocytes are assessed by flow cytometry. Half the patients will also undergo pre- and postoperative functional magnetic resonance imaging scans. 32-channel intraoperative electroencephalogram (EEG) recordings will be performed to identify intraoperative EEG correlates of neuroinflammation and/or postoperative cognitive resilience. Eighty patients will also undergo home sleep apnea testing to determine the relationships between sleep apnea severity, neuroinflammation, and impaired postoperative cognition. Additional assessments will help evaluate relationships between delirium, POCD, and other geriatric syndromes. CONCLUSION INTUIT will use a transdisciplinary approach to study the role of neuroinflammation in postoperative delirium and cognitive dysfunction and their associated functional brain connectivity changes, and it may identify novel targets for treating and/or preventing delirium and POCD and their sequelae. J Am Geriatr Soc 67:794-798, 2019.