title: Preoperative protein profiles in cerebrospinal fluid in elderly hip fracture patients at risk for delirium: A proteomics and validation study.
abstract: BACKGROUND
  A neuroinflammatory response is suggested to play an important role in delirium, a common complication in older hospitalized patients. We examined whether hip fracture patients who develop postoperative delirium have a different proteome in cerebrospinal fluid (CSF) prior to surgery.
  
  
  METHODS
  Patients (≥ 75 years) were admitted for hip fracture surgery. CSF was collected during spinal anaesthesia; proteins were separated using gel electrophoresis and identified with mass spectrometry. We compared the proteome of patients with and without postoperative delirium. Findings were validated in an independent, comparable cohort using immuno-assays.
  
  
  RESULTS
  In the derivation cohort 53 patients were included, 35.8% developed postoperative delirium. We identified differences in levels of eight CSF proteins between patients with and without subsequent delirium: complement factor C3, contactin-1, fibulin-1 and I-beta-1,3-N-acetylglucosaminyltransferase were significantly lower in patients with postoperative delirium, while neural cell adhesion molecule-2, fibrinogen, zinc-α-2-glycoprotein and haptoglobin levels were significantly higher. In the validation cohort 21.2% of 52 patients developed postoperative delirium. Immuno-assays confirmed contactin-1 results although not statistically significant. Complement factor C3 was significantly higher in patients with postoperative delirium.
  
  
  CONCLUSIONS
  Our results show the complexity of pathophysiological mechanisms involved in delirium and emphasizes the need of independent validation of findings.
  
  
  CONCLUSIONS
  This study highlights the challenges and inconsistent findings in studies of delirium, a serious complication in older patients. We analysed proteins in CSF, the most proximal fluid to the brain. All patients were free from delirium at the time of sampling.
authors.affiliation: Department of Neurology, Academic Medical Center, PO box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: Dunja
authors.initials: D
authors.lastname: Westhoff
authors.affiliation: Department of Geriatrics, Medical Center Alkmaar, Wilhelminalaan 12, 1815 JD Alkmaar, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Witlox
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Corneli
authors.initials: C
authors.lastname: van Aalst
authors.affiliation: Department of Geriatrics, Academic Medical Center, PO box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: Rikie M
authors.initials: RM
authors.lastname: Scholtens
authors.affiliation: Department of Geriatrics, Academic Medical Center, PO box 22660, 1100 DD Amsterdam, The Netherlands ; Department of Geriatrics, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Sophia E
authors.initials: SE
authors.lastname: de Rooij
authors.affiliation: Department of Geriatrics, Academic Medical Center, PO box 22660, 1100 DD Amsterdam, The Netherlands ; Department of Geriatrics, Gelre hospitals, Albert Schweitzerlaan 31, 7334 DZ Apeldoorn, The Netherlands.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: van Munster
authors.affiliation: Department of Geriatrics, Medical Center Alkmaar, Wilhelminalaan 12, 1815 JD Alkmaar, The Netherlands.
authors.forename: Jos F M
authors.initials: JF
authors.lastname: de Jonghe
authors.affiliation: Department of Surgery, Medical Center Alkmaar, Wilhelminalaan 12, 1815 JD Alkmaar, The Netherlands ; Trial Center Holland Health, Alkmaar, The Netherlands.
authors.forename: Alexander P J
authors.initials: AP
authors.lastname: Houdijk
authors.affiliation: GGZinGeest, Postbus 74077, 1070 BB Amsterdam, The Netherlands.
authors.forename: Piet
authors.initials: P
authors.lastname: Eikelenboom
authors.affiliation: Department of Intensive Care Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: David J
authors.initials: DJ
authors.lastname: van Westerloo
authors.affiliation: Department of Neurology, Academic Medical Center, PO box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: Diederik
authors.initials: D
authors.lastname: van de Beek
authors.affiliation: Department of Neurology, Academic Medical Center, PO box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: Willem A
authors.initials: WA
authors.lastname: van Gool
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Koenderman
keywords: 2D-DIGE, Two-dimensional difference gel electrophoresis; C3, Third component of the complement system; CSF; CSF, Cerebrospinal fluid; Delirium; ELISA, Enzyme linked immunosorbent assay; IQR, Interquartile range; LC-MS/MS, Liquid chromatography–mass spectrometry; Neuroinflammation; Proteomics; SDS-PAGE, Sodium dodecyl sulfate polyacrylamide gel electrophoresis; Validation; b3GNT3, N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase