1. The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer’s Disease: Results of a Randomized Trial
- Author
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Joseph P. Mathew, Michael L. James, David L. McDonagh, Miles Berger, Vikram Ponnusamy, David S. Warner, Mary Cooter, Mad-Pia trial team, Mark F. Newman, Leslie M. Shaw, Jacob W. Nadler, Wenjing Qi, Ellen Bennett, Daniel T. Laskowitz, and Allan H. Friedman
- Subjects
Male ,Genotype ,Amyloid beta ,Tau protein ,tau Proteins ,Article ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Alzheimer Disease ,030202 anesthesiology ,mental disorders ,Humans ,Medicine ,Propofol ,Amyloid beta-Peptides ,Isoflurane ,biology ,business.industry ,General Neuroscience ,Genetic Variation ,General Medicine ,Perioperative ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Clinical Psychology ,Anesthesia ,Anesthetic ,Anesthesia, Intravenous ,biology.protein ,Female ,Geriatrics and Gerontology ,Alzheimer's disease ,business ,Anesthetics, Intravenous ,Biomarkers ,030217 neurology & neurosurgery ,medicine.drug - Abstract
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.
- Published
- 2016