The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial.

Journal Article (Journal Article)

BACKGROUND: 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). OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Full Text

Duke Authors

Cited Authors

  • Berger, M; Nadler, JW; Friedman, A; McDonagh, DL; Bennett, ER; Cooter, M; Qi, W; Laskowitz, DT; Ponnusamy, V; Newman, MF; Shaw, LM; Warner, DS; Mathew, JP; James, ML; MAD-PIA trial team,

Published Date

  • April 15, 2016

Published In

Volume / Issue

  • 52 / 4

Start / End Page

  • 1299 - 1310

PubMed ID

  • 27079717

Pubmed Central ID

  • PMC5938737

Electronic International Standard Serial Number (EISSN)

  • 1875-8908

Digital Object Identifier (DOI)

  • 10.3233/JAD-151190


  • eng

Conference Location

  • Netherlands