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.
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Duke Authors
- Berger, Miles
- Carter Jr., James Harvey
- Friedman, Allan Howard
- James, Michael Lucas
- Lad, Shivanand
- Laskowitz, Daniel Todd
- Li, Yi-Ju
- Mathew, Joseph P.
- Newman, Mark Franklin
- Sampson, John Howard
- Zomorodi, Ali Reza
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
Language
- eng
Conference Location
- Netherlands