本研究旨在确定与手术后延迟神经认知恢复（dNCR）发展相关的术前血液生物标志物。共评估了67名接受头颈肿瘤切除术的全身麻醉患者（≥65岁），并使用迷你精神状态检查（MMSE）和蒙特利尔认知评估（MoCA）进行评估。术前血清代谢组学采用广泛靶向代谢组学技术进行确定。在这67名患者中，发现25例患者发展为dNCR，并与其余42例未发展为dNCR的患者中随机选择的25例患者进行匹配。根据正交部分最小二乘判别分析中的重要变量投影>1.0的标准，虚拟发现率<0.05，以及折叠变化>1.2或<0.83以减少误报阳性，选择了差异代谢物。术前血清草酸乙酰甲酯（OR: 1.054，95% CI: 1.027-1.095，P = 0.001）和2-氨基己二酸（2-AAA）（OR: 1.181，95% CI: 1.087-1.334，P = 0.001）在麻醉持续时间、教育和年龄调整后与术后dNCR相关。草酸乙酰甲酯和2-AAA的曲线下面积分别为0.86（灵敏度：0.84，特异度：0.88）和0.86（灵敏度：0.84，特异度：0.84）。在年龄、教育水平和手术时间调整后，术前高水平的草酸乙酰甲酯和2-AAA也与术后MoCA（β: 0.022，95% CI: 0.005-0.04，P = 0.013，针对草酸乙酰甲酯；β: 0.077，95% CI: 0.016-0.137，P = 0.014，针对2-AAA）和MMSE（β: 0.024，95% CI: 0.009-0.039，P = 0.002，针对草酸乙酰甲酯；β: 0.083，95% CI: 0.032-0.135，P = 0.002，针对2-AAA）评分降低相关。术前高血液水平的草酸乙酰甲酯和2-AAA与术后dNCR风险增加相关。

This study aimed to identify preoperative blood biomarkers related to development of delayed neurocognitive recovery (dNCR) following surgery.A total of 67 patients (≥65 years old) who underwent head and neck tumor resection under general anesthesia were assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Preoperative serum metabolomics were determined using widely targeted metabolomics technology.Of the 67 patients, 25 developed dNCR and were matched to 25 randomly selected patients from the remaining 42 without dNCR. Differential metabolites were selected using the criteria of variable importance in projection > 1.0 in orthogonal partial least squares discrimination analysis, false discovery rate <0.05, and fold-change >1.2 or <0.83 to minimize false positives. Preoperative serum levels of oxaloacetate (OR: 1.054, 95% CI: 1.027-1.095, P = 0.001) and 2-aminoadipic acid (2-AAA) (OR: 1.181, 95% CI: 1.087-1.334, P = 0.001) were associated with postoperative dNCR after adjusting for anesthesia duration, education, and age. Areas under the curve for oxaloacetate and 2-AAA were 0.86 (sensitivity: 0.84, specificity: 0.88) and 0.86 (sensitivity: 0.84, specificity: 0.84), respectively. High levels of preoperative oxaloacetate and 2-AAA also were associated with postoperative decreased MoCA (β: 0.022, 95% CI: 0.005-0.04, P = 0.013 for oxaloacetate; β: 0.077, 95%CI: 0.016-0.137, P = 0.014 for 2-AAA) and MMSE (β: 0.024, 95% CI: 0.009-0.039, P = 0.002 for oxaloacetate; β: 0.083, 95% CI: 0.032-0.135, P = 0.002 for 2-AAA) scores after adjusting for age, education level, and operation time.High preoperative blood levels of oxaloacetate and 2-AAA were associated with increased risk of postoperative dNCR.https://classic.clinicaltrials.gov/ct2/show/NCT05105451, identifier NCT05105451.Copyright © 2023 Mao, Huang, Zhou, Zhu, Yan, Jiang and Zhang.