Forskning ved Københavns Universitet - Københavns Universitet


Biomarkers of Cerebral Injury for Prediction of Postoperative Cognitive Dysfunction in Patients Undergoing Cardiac Surgery

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Objectives: To assess the ability of the biomarkers neuron-specific enolase (NSE), tau, neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP) to predict postoperative cognitive dysfunction (POCD) at discharge in patients who underwent cardiac surgery. Design: Post hoc analyses (with tests being prespecified before data analyses) from a randomized clinical trial. Setting: Single-center study from a primary heart center in Denmark. Participants: Adult patients undergoing elective or subacute on-pump coronary artery bypass grafting and/or aortic valve replacement. Interventions: Blood was collected before induction of anesthesia, after 24 hours, after 48 hours, and at discharge from the surgical ward. The International Study of Postoperative Cognitive Dysfunction test battery was applied to diagnose POCD at discharge and after three months. Linear mixed models of covariance were used to assess whether repeated measurements of biomarker levels were associated with POCD. Receiver operating characteristic (ROC) curves were applied to assess the predictive value of each biomarker measurement for POCD. Measurements and Main Results: A total of 168 patients had biomarkers measured at baseline, and 47 (28%) fulfilled the POCD criteria at discharge. Patients with POCD at discharge had significantly higher levels of tau (p = 0.02) and GFAP (p = 0.01) from baseline to discharge. The biomarker measurements achieving the highest area under the ROC curve for prediction of POCD at discharge were NFL measured at discharge (AUC, 0.64; 95% confidence interval [CI], 0.54-0.73), GFAP measured 48 hours after induction (AUC, 0.64; 95% CI, 0.55-0.73), and GFAP measured at discharge (AUC, 0.64; 95% CI, 0.54-0.74), corresponding to a moderate predictive ability. Conclusions: Postoperative serum levels of tau and GFAP were elevated significantly in patients with POCD who underwent cardiac surgery at discharge; however, the biomarkers achieved only modest predictive abilities for POCD at discharge. Postoperative levels of NSE were not associated with POCD at discharge.

TidsskriftJournal of Cardiothoracic and Vascular Anesthesia
StatusAccepteret/In press - 2021

Bibliografisk note

Funding Information:
The study was funded by the Danish Heart Foundation (24-R97-A5179-22868 and 15-R99-A6034-22905); the Research Foundations at Rigshospitalet (E-22329-01), University of Copenhagen, Denmark; the Lundbeck Foundation (R186-2015-2132); the Swedish Research Council (#2017-00915; #2018-02532); the Alzheimer Drug Discovery Foundation (ADDF), United States (#201809-2016615; #201809-2016862); the European Research Council (#681712); the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243); and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986; #ALFGBG-720931), and European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236). HZ is a Wallenberg Scholar.

Funding Information:
H.Z. has served on scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, and CogRx; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, and Biogen; and is a cofounder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. K.B. has served as a consultant or on advisory boards for Abcam, Axon, Biogen, Lilly, MagQu, Novartis, and Roche Diagnostics and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg. The other authors report no conflicts of interest.

Publisher Copyright:
© 2021 Elsevier Inc.

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