High preoperative blood oxaloacetate and 2-aminoadipic acid levels are associated with postoperative delayed neurocognitive recovery

Front Endocrinol (Lausanne). 2023 Jul 31:14:1212815. doi: 10.3389/fendo.2023.1212815. eCollection 2023.

Abstract

Introduction: This study aimed to identify preoperative blood biomarkers related to development of delayed neurocognitive recovery (dNCR) following surgery.

Methods: 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.

Results: 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.

Conclusion: High preoperative blood levels of oxaloacetate and 2-AAA were associated with increased risk of postoperative dNCR.

Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT05105451, identifier NCT05105451.

Keywords: 2-aminoadipic acid; anesthesia; delayed neurocognitive recovery; metabolomics; oxaloacetate.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Aminoadipic Acid*
  • Aged
  • Humans
  • Mental Status and Dementia Tests
  • Oxaloacetic Acid*

Substances

  • 2-Aminoadipic Acid
  • Oxaloacetic Acid

Associated data

  • ClinicalTrials.gov/NCT05105451

Grants and funding

This research was supported by National Natural Science Foundation of China (81970990, 82071177, and 82171173); Natural Science Foundation of Shanghai (21dz1200205, 22ZR1437200, and 22YF1422500); Clinical Research Program of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (JYLJ202221); Shanghai Jiao Tong University School of Medicine Two-hundred Talent (20191818); and Cross-disciplinary Research Fund of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (JYJC202002).