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Neuroinflammatory markers associate with cognitive decline after major surgery: Findings of an explorative study

Journal article
Authors Mattias Danielson
A. Wiklund
F. Granath
Kaj Blennow
S. Mkrtchian
Bengt Nellgård
Jonatan Oras
M. J. Fagerlund
A. Granstrom
A. Schening
L. S. Rasmussen
H. E. Harris
Henrik Zetterberg
Sven-Erik Ricksten
L. I. Eriksson
Published in Annals of Neurology
Volume 87
Issue 3
Pages 370-382
ISSN 0364-5134
Publication year 2020
Published at Institute of Clinical Sciences, Department of Anesthesiology and Intensive care
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 370-382
Language en
Keywords dysfunction, inflammation, brain, Neurosciences & Neurology
Subject categories Neurology, Neurochemistry


Objective Long-term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long-term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long-term cognitive decline defined as a composite cognitive z score of >= 1.0 compared to patients without long-term cognitive decline at 3 months postsurgery. Methods Serum and CSF biomarkers of inflammation and blood-brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively. Results Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48-hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long-term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long-term cognitive decline at 3 months. Patients both with and patients without long-term cognitive decline showed early transient increases of the astroglial biomarkers S-100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio). Interpretation Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long-term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort.

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