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Region Hovedstaden - en del af Københavns Universitetshospital
E-pub ahead of print

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 ≥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, while cognitive function was assessed preoperatively, 2-5 days and three 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 two first principal component (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated to long-term cognitive decline at 3 months, while none of the PC construct serum variables showed a significant association to long-term cognitive decline at 3 months. Both patients with and 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 post-surgery. The findings of this explorative study require validation in a larger surgical patient cohort. This article is protected by copyright. All rights reserved.

OriginalsprogEngelsk
TidsskriftAnnals of Neurology
ISSN0364-5134
DOI
StatusE-pub ahead of print - 12 jan. 2020

Bibliografisk note

This article is protected by copyright. All rights reserved.

ID: 58974321