Associations between systemic inflammation and cognitive trajectories post-stroke

Our objective was to explore whether plasma inflammatory biomarkers and related metabolites in acute phase and 3 months after stroke were associated with different cognitive trajectories and with changes in cognition post-stroke. The Norwegian Cognitive Impairment After Stroke (Nor-COAST) study was a prospective, multicentre cohort study of patients with acute stroke, followed up at 3, 18, and 36 months post-stroke. First, we modelled cognitive trajectory groups based on Montreal Cognitive Assessment (MoCA) scores and used multinominal logistic regression to study the associations between systemic inflammatory biomarkers/metabolites and group membership. Second, using mixed linear regression, we investigated whether the same biomarkers/metabolites were associated with changes in MoCA scores over time, stratified by pre-stroke cognitive status. The 466 participants had mean (SD) age 72 (12) years, 59% were males, and mean (SD) NIHSS score at admittance was 4 (4.8). Higher acute-phase values of the terminal complement complex, interleukin 6, macrophage inflammatory protein 1α, neopterin, quinolinic acid, and PA ratio = 4-pyridoxic acid / (pyridoxal + pyridoxal 5'-phosphate) and higher 3-month values of neopterin were associated with increased risk of being in the group characterized by low and declining MoCA score compared to the group of best MoCA score (p < 0.01). Higher acute-phase values of tumour necrosis factor and interleukin 8, were associated with progressive decline in the MoCA score (p < 0.01). Premorbid factors, and in particular pre-stroke frailty, had more impact on the models than stroke-related factors, and partly confounded several of these associations. Higher degrees of systemic inflammation in the acute phase were associated with worse cognitive trajectories and may reflect the response to the acute stroke, stroke-related complications and/or premorbid conditions.Trial registration: ClinicalTrials.gov: NCT02650531. Retrospectively registered January 8, 2016. First participant included May 18, 2015.