title: The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial.
abstract: Preclinical studies have found differential effects of isoflurane and propofol on the Alzheimer's disease (AD)-associated markers tau, phosphorylated tau (p-tau) and amyloid-β (Aβ).
  
  
  
  We asked whether isoflurane and propofol have differential effects on the tau/Aβ ratio (the primary outcome), and individual AD biomarkers. We also examined whether genetic/intraoperative factors influenced perioperative changes in AD biomarkers.
  
  
  
  Patients undergoing neurosurgical/otolaryngology procedures requiring lumbar cerebrospinal fluid (CSF) drain placement were prospectively randomized to receive isoflurane (n = 21) or propofol (n = 18) for anesthetic maintenance. We measured perioperative CSF sample AD markers, performed genotyping assays, and examined intraoperative data from the electronic anesthesia record. A repeated measures ANOVA was used to examine changes in AD markers by anesthetic type over time.
  
  
  
  The CSF tau/Aβ ratio did not differ between isoflurane- versus propofol-treated patients (p = 1.000). CSF tau/Aβ ratio and tau levels increased 10 and 24 h after drain placement (p = 2.002×10-6 and p = 1.985×10-6, respectively), mean CSF p-tau levels decreased (p = 0.005), and Aβ levels did not change (p = 0.152). There was no interaction between anesthetic treatment and time for any of these biomarkers. None of the examined genetic polymorphisms, including ApoE4, were associated with tau increase (n = 9 polymorphisms, p > 0.05 for all associations).
  
  
  
  Neurosurgery/otolaryngology procedures are associated with an increase in the CSF tau/Aβ ratio, and this increase was not influenced by anesthetic type. The increased CSF tau/Aβ ratio was largely driven by increases in tau levels. Future work should determine the functional/prognostic significance of these perioperative CSF tau elevations.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Miles
authors.initials: M
authors.lastname: Berger
authors.affiliation: Division Chief, Neurosurgical Anesthesiology Medical Director, Postanesthesia Care Unit; Department of Anesthesiology, University of Rochester, Rochester, NY, USA.
authors.forename: Jacob W
authors.initials: JW
authors.lastname: Nadler
authors.affiliation: Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Friedman
authors.affiliation: Department of Anesthesiology & Pain Management, Neurological Surgery, Neurology and Neurotherapeutics, University of Texas, Southwestern, Dallas, TX, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: McDonagh
authors.affiliation: Department of Neurology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Bennett
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Cooter
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Qi
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.|Department of Neurology, Duke University Medical Center, Durham, NC, USA.|Department of Neurobiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Laskowitz
authors.affiliation: College of Arts and Sciences, Duke University, Durham, NC, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Ponnusamy
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.|Private Diagnostic Clinic, Duke University Medical Center, Durham, NC, USA.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Newman
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.|Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.|Department of Neurobiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mathew
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.|Department of Neurology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: James
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000235:genetics; D000771:Anesthesia, Intravenous / Q000379:methods; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D015742:Propofol / Q000494:pharmacology*; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D018686:Anesthetics, Intravenous; D015415:Biomarkers; D016875:tau Proteins; D007530:Isoflurane; D015742:Propofol
keywords: Amyloid-beta; anesthesia; cerebrospinal fluid; isoflurane; propofol; surgery; tau protein