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

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  • Mattias Danielson
  • Andreas Wiklund
  • Fredrik Granath
  • Kaj Blennow
  • Souren Mkrtchian
  • Bengt Nellgård
  • Jonatan Oras
  • Malin Jonsson Fagerlund
  • Anna Granström
  • Anna Schening
  • Lars S Rasmussen
  • Helena Erlandsson Harris
  • Henrik Zetterberg
  • Sven-Erik Ricksten
  • Lars I Eriksson
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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. Ann Neurol 2020;87:370–382.

Original languageEnglish
JournalAnnals of Neurology
Volume87
Issue number3
Pages (from-to)370-382
Number of pages13
ISSN0364-5134
DOIs
Publication statusPublished - Mar 2020

Bibliographical note

© 2020 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

ID: 58974321