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

MAD-PIA investigators

Research output: Contribution to journalArticle

20 Citations (Scopus)

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. Future work should determine the functional/prognostic significance of these perioperative CSF tau elevations.

Original languageEnglish (US)
Pages (from-to)1299-1310
Number of pages12
JournalJournal of Alzheimer's Disease
Volume52
Issue number4
DOIs
StatePublished - Jan 1 2016

Fingerprint

Isoflurane
Propofol
Cerebrospinal Fluid
Alzheimer Disease
Anesthesia
Anesthetics
Biomarkers
Otolaryngology
Apolipoprotein E4
Neurosurgical Procedures
Neurosurgery
Genetic Polymorphisms
Amyloid
Analysis of Variance
Maintenance

Keywords

  • Amyloid-beta
  • anesthesia
  • cerebrospinal fluid
  • isoflurane
  • propofol
  • surgery
  • tau protein

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

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

In: Journal of Alzheimer's Disease, Vol. 52, No. 4, 01.01.2016, p. 1299-1310.

Research output: Contribution to journalArticle

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title = "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. Future work should determine the functional/prognostic significance of these perioperative CSF tau elevations.",
keywords = "Amyloid-beta, anesthesia, cerebrospinal fluid, isoflurane, propofol, surgery, tau protein",
author = "{MAD-PIA investigators} and Miles Berger and Nadler, {Jacob W.} and Allan Friedman and McDonagh, {David L.} and Bennett, {Ellen R.} and Mary Cooter and Wenjing Qi and Laskowitz, {Daniel T.} and Vikram Ponnusamy and Newman, {Mark F.} and Shaw, {Leslie M.} and Warner, {David S.} and Mathew, {Joseph P.} and James, {Michael L.} and Senthil Radhakrishnan and James Carter and Shivanandan Lad and Ali Zomorodi and John Sampson and Takanori Fukushima and Owoicho Adogwa and Karen Clemmons and Carlos Conde and Omowunmi Olaleye and Naraida Balajonda and Jhoanna Aquino and Bonita Funk and Li, {Yi Ju}",
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T1 - The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease

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AU - Berger, Miles

AU - Nadler, Jacob W.

AU - Friedman, Allan

AU - McDonagh, David L.

AU - Bennett, Ellen R.

AU - Cooter, Mary

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AU - Laskowitz, Daniel T.

AU - Ponnusamy, Vikram

AU - Newman, Mark F.

AU - Shaw, Leslie M.

AU - Warner, David S.

AU - Mathew, Joseph P.

AU - James, Michael L.

AU - Radhakrishnan, Senthil

AU - Carter, James

AU - Lad, Shivanandan

AU - Zomorodi, Ali

AU - Sampson, John

AU - Fukushima, Takanori

AU - Adogwa, Owoicho

AU - Clemmons, Karen

AU - Conde, Carlos

AU - Olaleye, Omowunmi

AU - Balajonda, Naraida

AU - Aquino, Jhoanna

AU - Funk, Bonita

AU - Li, Yi Ju

PY - 2016/1/1

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N2 - 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. Future work should determine the functional/prognostic significance of these perioperative CSF tau elevations.

AB - 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. Future work should determine the functional/prognostic significance of these perioperative CSF tau elevations.

KW - Amyloid-beta

KW - anesthesia

KW - cerebrospinal fluid

KW - isoflurane

KW - propofol

KW - surgery

KW - tau protein

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