Longitudinal plasma interleukin‐6 and post‐stroke cognitive outcomes: The Stroke‐IMPaCT study

INTRODUCTION: Inflammatory factors, particularly interleukin (IL)-6, are implicated in post-stroke cognitive decline, yet the association with longitudinal changes in these markers remains unclear. METHODS: Plasma IL-6 and other inflammatory markers were measured within 96 hours of ischemic stroke, and at 6-9 and 18-21 months, alongside cognitive assessment. Associations between inflammatory factors and cognition were examined using adjusted regression models. RESULTS: A doubling of IL-6 between admission and 6-9 months was associated with cognitive impairment at 18-21 months (odds ratio [OR] = 8.16; 95% confidence interval [CI] 1.82-47.26; p = 0.01), while each one-unit IL-6 increase was linked to a 1.5-point decrease in memory Z-scores (β = -1.50; 95% CI -2.57-0.43; p = 0.007). Smokers showed persistently blunted IL-6 trajectories (p < 0.05) and downregulated Toll-like receptor signaling (p < 0.05). Exploratory analyses suggested that lower socioeconomic status may relate to 6-month IL-6 concentrations via smoking. DISCUSSION: Post-stroke IL-6 trajectories associate with later cognition, highlighting potential therapeutic targets.