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

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 24h 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. Futurework should determine the functional/prognostic significance of these perioperative CSF tau elevations.

Factors Influencing Clinical Correlates of Chronic Traumatic Encephalopathy (CTE): a Review

“…Jiang and Jiang (2015) drew similar conclusions from their review, noting that commonly used inhaled anesthetics induce pro-apoptotic signaling, and increase the synthesis and accumulation of beta-amyloid and hyperphosphorylated tau. A randomized trial examining differential effects of anesthesia type found elevated levels of tau in cerebrospinal fluid following surgery, but no difference in degree of elevation based on use of isoflurane versus propofol (Berger et al 2016). Taken together, evidence indicates exposure to surgery and general anesthesia increases risk for development of neuropathology; however, there is a lack of support for general anesthesia leading to clinically diagnosed dementia.…”

Neuroinflammatory challenges compromise neuronal function in the aging brain: Postoperative cognitive delirium and Alzheimer’s disease

“…This hypothesis is supported by a number of studies that identified links between anesthetics and cognitive decline, memory impairments, and increases in AD-related biomarkers [25–27]. However, additional studies provide evidence that exposure to anesthesia has no effect on cognition or the expression of AD biomarkers [28,29]. The second hypothesis, and the one we will focus on in this review, proposes that declines in cognition occur as a result of neuroinflammatory cascades that are activated by the invasive nature of surgical procedures [30].…”

“…Recent clinical studies have found that the incidence for dementia and AD is unchanged in patients with exposure to general anesthesia during surgery [28], with cognitive functions unaffected by anesthetics (sevoflurane) [36,37]. An additional study found that levels of AD biomarkers (tau and Aβ) were increased following surgical procedure, but were unaffected by anesthesia exposure alone [29]. Animal studies find that the anesthetic sevoflurane alone has no effect on contextual fear memory or synaptic plasticity/connectivity in the medial pre-frontal cortex, but in combination with a surgical procedure did impair memory and connectivity [38].…”

The INTUIT Study: Investigating Neuroinflammation Underlying Postoperative Cognitive Dysfunction

“…14 CSF tau levels are measured before surgery and 24 hours and 6 weeks after surgery at the Alzheimer's Disease Neuroimaging Initiative biomarker core lab 14 that has well-validated multiplex ELISA-based bead assays for CSF tau, phospho-tau, and amyloid-beta levels. 30 To avoid measurement bias, sample measurements are performed in random order, and technicians are blinded to study subject number and time point. To minimize confounding from diurnal variation, CSF samples per patient are collected at the same time of day (AE 1 h) whenever possible.…”