Journal
ANNALS OF NEUROLOGY
Volume 87, Issue 3, Pages 370-382Publisher
WILEY
DOI: 10.1002/ana.25678
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Funding
- Swedish State Support for Clinical Research [ALFGBG-721141, ALFGBG-144341, ALFGBG-139671, ALFGBG-75130, ALFGBG-720931 SLL20140188, SLL20170127]
- Gothenburg Medical Society
- Swedish Research Council [K2016-01122, K2010-61X-14002, K2010-63P21562-01-4, K2015-02776-3, K2011-61X-20401-05-6, 2018-02532]
- European Research Council [681712]
- Knut and Alice Wallenberg Foundation
- Olav Thon Foundation
- Torsten Soderberg Foundation [FO2019-0059]
- Frimurarestiftelsen, Hjarnfonden [FO2019-0059]
- Stockholms Lans Landsting [20170127]
- Vetenskapsradet [2016-01122]
- Swedish Research Council [2016-01122] Funding Source: Swedish Research Council
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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
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