Prediction of postoperative delirium after cardiac surgery by the interplay between preoperative plasma p-tau181 and IL-6 and heart-brain axis related factors: results from the prospective observational study FINDERI.

Journal: Molecular psychiatry
Published Date: Dec 22, 2025

Abstract

Postoperative delirium (POD) following cardiac surgery is a severe complication. There is evidence of a link between neuroinflammation and neurodegeneration in POD. We investigated the preoperative proinflammatory interleukin-6 (IL-6) and neuronal damage marker phosphorylated tau protein 181 (p-tau181) to POD while considering preoperative heart-brain axis related factors. The prospective FINd DElirium RIsk factors (FINDERI) is an observational study in patients undergoing cardiac surgery. Biomarkers IL-6 and p-tau181 were measured in blood samples. For statistics, we utilized multiple logistic regression analyses and advanced machine learning techniques. In 491 patients, 106 (21.6%) developed POD. The age of patients with POD was significantly higher than that of patients without POD (p < 0.001). Preoperative IL-6 and p-tau181 levels independently predicted POD [IL-6: area under the curve (AUC) = 0.605, p < 0.005; p-tau181: AUC = 0.641, p < 0.0001)]. A multiple logistic regression analysis of preoperative log-transformed biomarkers levels (p-tau181, IL-6), female sex and cognitive performance increased the AUC (0.710, p < 0.0001) in predicting POD. We created a decision tree prediction model including preoperative p-tau181, IL-6, and the severity of mitral valve disease (training data: AUC = 0.672, p < 0.0001; validation data: AUC = 0.642, p < 0.05). The LASSO regression showed an increased AUC in the training (0.751, p < 0.0001) and validation dataset (0.652, p < 0.05). Our results demonstrate that the combined assessment of preoperatively measured p-tau181 and IL-6, preoperative mitral valve disease, cognitive performance and female sex, significantly predicts POD. These findings provide evidence that neuroinflammation and neuronal cell damage are associated with POD.

Authors

  • Niels Hansen
    Department of Psychiatry and Psychotherapy (NH, HE, JW), University of Göttingen Medical Center, Göttingen, Germany.
  • Clara Maria Knopp
    Department of Geriatrics, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.
  • Hermann Esselmann
    Department of Psychiatry and Psychotherapy (NH, HE, JW), University of Göttingen Medical Center, Göttingen, Germany.
  • Christopher M Celano
    Department of Psychiatry (MS, CMC), Massachusetts General Hospital, Boston, MA; Department of Psychiatry (CMC), Harvard Medical Schol, Boston, MA.
  • Carlotta Derad
    Department of Medical Statistics (CD, TA), University of Göttingen Medical Center, Göttingen, Germany.
  • Thomas Asendorf
    Department of Medical Statistics (CD, TA), University of Göttingen Medical Center, Göttingen, Germany.
  • Mohammed Chebbok
    Department of Geriatrics (MS, MC, SH, AW, JS, FEB, JE, CAFA), University of Göttingen Medical Center, Göttingen, Germany; Department of Cardiology and Pneumology (MC), University of Göttingen Medical Center, Göttingen, Germany.
  • Stephanie Heinemann
    Department of Geriatrics (MS, MC, SH, AW, JS, FEB, JE, CAFA), University of Göttingen Medical Center, Göttingen, Germany.
  • Ihtzaz Malik
    Department of Geriatrics, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.
  • Barbara Morgado
    Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.
  • Matilda-Marie Becker
    Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.
  • Irina Günther
    Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.
  • Iryna Krasiuk
    Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.
  • Katharina Packroß
    Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.
  • Alina Isabel Rediske
    Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.
  • Nicholas Paul Süttmann
    Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.
  • Tobias Titsch
    Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.
  • Ingo Kutschka
    Clinic for Cardiothoracic and Vascular Surgery/Heart Center, University Medical Center Göttingen, Robert-Koch Str. 40, 37075 Göttingen, Germany.
  • Hassina Baraki
    Department of Cardiovascular and Thoracic Surgery (MS, IK, HB), University of Göttingen Medical Center, Göttingen, Germany; DZHK (German Center for Cardiovascular Research) (MS, IK, HB, CAFA), Göttingen, Germany.
  • Jens Wiltfang
    Department of Psychiatry and Psychotherapy (NH, HE, JW), University of Göttingen Medical Center, Göttingen, Germany; German Center for Neurodegenerative Diseases (DZNE) (JW), Göttingen, Germany; Neurosciences and Signaling Group (JW), Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.
  • Christine A F von Arnim
    Department of Geriatrics (MS, MC, SH, AW, JS, FEB, JE, CAFA), University of Göttingen Medical Center, Göttingen, Germany; DZHK (German Center for Cardiovascular Research) (MS, IK, HB, CAFA), Göttingen, Germany.
  • Monika Sadlonova
    Department of Cardiovascular and Thoracic Surgery (MS, IK, HB), University of Göttingen Medical Center, Göttingen, Germany; Department of Geriatrics (MS, MC, SH, AW, JS, FEB, JE, CAFA), University of Göttingen Medical Center, Göttingen, Germany; Department of Psychosomatic Medicine and Psychotherapy (MS,), University of Göttingen Medical Center, Göttingen, Germany; DZHK (German Center for Cardiovascular Research) (MS, IK, HB, CAFA), Göttingen, Germany; Department of Psychiatry (MS, CMC), Massachusetts General Hospital, Boston, MA. Electronic address: [email protected].

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