%0 Journal Article %J J Alzheimers Dis %D 2016 %T The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial. %A Berger, Miles %A Nadler, Jacob W %A Friedman, Allan %A McDonagh, David L %A Bennett, Ellen R %A Cooter, Mary %A Qi, Wenjing %A Laskowitz, Daniel T %A Ponnusamy, Vikram %A Newman, Mark F %A Shaw, Leslie M %A Warner, David S %A Mathew, Joseph P %A James, Michael L %X

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.

%B J Alzheimers Dis %V 52 %P 1299-310 %8 2016 Apr 15 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/27079717?dopt=Abstract %R 10.3233/JAD-151190