Plasma Inflammatory Biomarkers Are Associated With Poststroke Cognitive Impairment: The Nor-COAST Study

Heidi Vihovde Sandvig; Stina Aam; Katinka Nordheim Alme; Torunn Askim; Mona K Beyer; Hanne Ellekjær; Hege Ihle-Hansen; Stian Lydersen; Tom Eirik Mollnes; Ragnhild Munthe-Kaas; Halvor Næss; Ingvild Saltvedt; Yngve Müller Seljeseth; Pernille Thingstad; Torgeir Wethal; Anne-Brita Knapskog

doi:10.1161/STROKEAHA.122.041965

Plasma Inflammatory Biomarkers Are Associated With Poststroke Cognitive Impairment: The Nor-COAST Study

Stroke. 2023 May;54(5):1303-1311. doi: 10.1161/STROKEAHA.122.041965. Epub 2023 Apr 7.

Authors

Heidi Vihovde Sandvig^{1

2}, Stina Aam^{2

3}, Katinka Nordheim Alme⁴, Torunn Askim², Mona K Beyer^{5

6}, Hanne Ellekjær^{2

7}, Hege Ihle-Hansen⁸, Stian Lydersen⁹, Tom Eirik Mollnes^{10

11

12}, Ragnhild Munthe-Kaas¹³, Halvor Næss^{14

15

16}, Ingvild Saltvedt^{2

3}, Yngve Müller Seljeseth¹⁷, Pernille Thingstad², Torgeir Wethal^{2

7}, Anne-Brita Knapskog¹⁸

Affiliations

¹ Department of Medicine, Kristiansund Hospital, Møre og Romsdal Hospital Trust, Norway (H.V.S.).
² Department of Neuromedicine and Movement Science (H.V.S., S.A., T.A., H.E., I.S., P.T., T.W.), NTNU - Norwegian University of Science and Technology, Trondheim.
³ Department of Geriatric Medicine, Clinic of Medicine, St. Olavs Hospital (S.A., I.S.), Trondheim University Hospital, Norway.
⁴ Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway (K.N.A.).
⁵ Division of Radiology and Nuclear Medicine (M.K.B.), Oslo University Hospital, Norway.
⁶ Institute of Clinical Medicine, University of Oslo, Norway (M.K.B.).
⁷ Department of Medicine, Stroke Unit (H.E., T.W.), Trondheim University Hospital, Norway.
⁸ Oslo Stroke Unit, Department of Neurology (H.I.-H.), Oslo University Hospital, Norway.
⁹ Department of Mental Health (S.L.), NTNU - Norwegian University of Science and Technology, Trondheim.
¹⁰ Faculty of Medicine and Health Science, and Centre of Molecular Inflammation Research (T.E.M.), NTNU - Norwegian University of Science and Technology, Trondheim.
¹¹ Department of Immunology, Oslo University Hospital and University of Oslo, Norway (T.E.M.).
¹² Research Laboratory, Nordland Hospital, Bodø, Norway (T.E.M.).
¹³ Department of Medicine, Bærum Hospital, Vestre Viken Hospital Trust, Drammen, Norway (R.M.-K.).
¹⁴ Department of Neurology, Haukeland University Hospital, Bergen, Norway (H.N.).
¹⁵ Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway (H.N.).
¹⁶ Institute of Clinical Medicine (K1), University of Bergen, Norway (H.N.).
¹⁷ Medical Department, Ålesund Hospital, Møre og Romsdal Hospital Trust, Norway (Y.M.S.).
¹⁸ Department of Geriatric Medicine (A.-B.K.), Oslo University Hospital, Norway.

Abstract

Background: Inflammation is proposed to be involved in the pathogenesis of poststroke cognitive impairment. The aim of this study was to investigate associations between concentrations of systemic inflammatory biomarkers after ischemic stroke and poststroke cognitive impairment.

Methods: The Nor-COAST study (Norwegian Cognitive Impairment After Stroke) is a prospective observational multicenter cohort study, including patients hospitalized with acute stroke between 2015 and 2017. Inflammatory biomarkers, including the TCC (terminal C5b-9 complement complex) and 20 cytokines, were analyzed in plasma, collected at baseline, 3-, and 18 months poststroke, using ELISA and a multiplex assay. Global cognitive outcome was assessed with the Montreal Cognitive Assessment (MoCA) scale. We investigated the associations between plasma inflammatory biomarkers at baseline and MoCA score at 3-, 18-, and 36-month follow-ups; the associations between inflammatory biomarkers at 3 months and MoCA score at 18- and 36-month follow-ups; and the association between these biomarkers at 18 months and MoCA score at 36-month follow-up. We used mixed linear regression adjusted for age and sex.

Results: We included 455 survivors of ischemic stroke. Higher concentrations of 7 baseline biomarkers were significantly associated with lower MoCA score at 36 months; TCC, IL (interleukin)-6, and MIP (macrophage inflammatory protein)-1α were associated with MoCA at 3, 18, and 36 months (P<0.01). No biomarker at 3 months was significantly associated with MoCA score at either 18 or 36 months, whereas higher concentrations of 3 biomarkers at 18 months were associated with lower MoCA score at 36 months (P<0.01). TCC at baseline and IL-6 and MIP-1α measured both at baseline and 18 months were particularly strongly associated with MoCA (P<0.01).

Conclusions: Higher concentrations of plasma inflammatory biomarkers were associated with lower MoCA scores up to 36 months poststroke. This was most pronounced for inflammatory biomarkers measured in the acute phase following stroke.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT02650531.

Keywords: biomarkers; cognition; inflammation; interleukin; stroke.

Publication types

Observational Study
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Cognitive Dysfunction* / etiology
Cohort Studies
Humans
Ischemic Stroke* / complications
Neuropsychological Tests
Stroke* / complications

Substances

Biomarkers

Associated data

ClinicalTrials.gov/NCT02650531