ABSTRACT NUMBER: ESOC2026A1418 IL-6 TRANS-SIGNALLING AND POST-STROKE COGNITIVE RECOVERY: LONGITUDINAL EVIDENCE FROM THE STROKE-IMPACT COHORT

Abstract Background and aims Post-stroke cognitive impairment is a major contributor to long-term disability, yet the mechanisms underlying cognitive recovery remain unclear. While interleukin-6 (IL-6) is linked to poorer cognitive outcomes post stroke, the role of IL-6 trans-signalling (measured by the B/T ratio) remains unexplored. This study investigated associations between IL-6 trans-signalling, longitudinal cognitive trajectories, and cerebrovascular imaging markers after ischaemic stroke. Methods In the multi-centre Stroke-IMPaCT cohort, plasma IL-6 trans-signalling components were measured at admission, 6 and 18 months post-stroke. Cognitive performance was assessed longitudinally using a comprehensive neuropsychological battery. Primary outcomes were the change in memory and processing speed between 6 and 18 months. Secondary outcomes included cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability at 6 months. Models were adjusted for age, sex, NIHSS, hypertension, study site, and time from symptom onset to blood draw. Results Mixed-effects modelling demonstrated longitudinal stability of the B/T ratio. Higher admission B/T ratios were associated with greater improvement in memory between 6 and 18 months (β = 1.63, 95% CI 0.29–2.97, n=105), with similar trends for processing speed. Higher admission B/T ratios were also associated with increased cerebral perfusion to the stroke site at 6 months (β = 31.5, 95% CI 2.51–60.6, n=55), with no association observed for BBB permeability. Conclusions Higher IL-6 trans-signalling is associated with improved cognitive recovery and increased cerebral perfusion after stroke. These findings suggest IL-6 trans signalling could promote post stroke recovery and highlight possible therapeutic strategies. Conflict of interest Natasha Carmichael: nothing to disclose. Aisling Fothergill: nothing to disclose. Olivia Jones: nothing to disclose. Lauren Drag: nothing to disclose. Marion Buckwalter: nothing to disclose. Laura Parkes: nothing to disclose.John Grainger: nothing to disclose. Stuart Allan: nothing to disclose. Craig Smith: nothing to disclose.