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<p>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 (<i>p</i> &lt; 0.001). Preoperative IL-6 and p-tau181 levels independently predicted POD [IL-6: area under the curve (AUC) = 0.605, <i>p</i> &lt; 0.005; p-tau181: AUC = 0.641, <i>p</i> &lt; 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, <i>p</i> &lt; 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, <i>p</i> &lt; 0.0001; validation data: AUC = 0.642, <i>p</i> &lt; 0.05). The LASSO regression showed an increased AUC in the training (0.751, <i>p</i> &lt; 0.0001) and validation dataset (0.652, <i>p</i> &lt; 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.</p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月22日

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  • Niels Hansen,
  • Clara Maria Knopp,
  • Hermann Esselmann,
  • Christopher M. Celano,
  • Carlotta Derad,
  • Thomas Asendorf,
  • Mohammed Chebbok,
  • Stephanie Heinemann,
  • Ihtzaz Malik,
  • Barbara Morgado,
  • Matilda-Marie Becker,
  • Irina Günther,
  • Iryna Krasiuk,
  • Katharina Packroß,
  • Alina Isabel Rediske,
  • Nicholas Paul Süttmann,
  • Tobias Titsch,
  • Ingo Kutschka,
  • Hassina Baraki,
  • Jens Wiltfang,
  • Christine A. F. von Arnim,
  • Monika Sadlonova,
  • Adriana Wiesent,
  • Anke Jahn-Brodmann,
  • Anne-Catherine Thiel,
  • Annika Gaß,
  • Barbara Morgado,
  • Björn Hendrik Schott,
  • Britta Albert,
  • Charlotte Eberhard,
  • Christine A. F. von Arnim,
  • Clara Maria Knopp,
  • Frederike E. Bauer,
  • Jessica Schmitz,
  • Julia Ehrentraut,
  • Maike Hohberg,
  • Manuel J. Santander,
  • Maria Alexy,
  • Maria Dornieden,
  • Maria Knierim,
  • Marianne Richter,
  • Melania Hotheit,
  • Michael Moser,
  • Miriam F. Schröder,
  • Paul T. Itting,
  • Rebecca Arentz,
  • Sandra Kastenbauer,
  • Santander Martinez,
  • Manuel Johannes,
  • Sophie Doerfler,
  • Tendai Chiwakata,
  • Theresa Maria Kruck

摘要

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.