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

## TL;DR

High levels of interleukin-6 in the months after a stroke are linked to worse long-term cognitive outcomes, suggesting a potential target for treatment.

## Contribution

This study identifies rising interleukin-6 levels as a stronger predictor of post-stroke cognitive decline than initial levels.

## Key findings

- A doubling of IL-6 between admission and 6–9 months was associated with cognitive impairment at 18–21 months.
- Smoking was linked to lower IL-6 levels and reduced Toll-like receptor signaling.
- Subacute IL-6 changes may help predict or guide interventions for cognitive outcomes after stroke.

## Abstract

Inflammatory factors, particularly interleukin (IL)‐6, are implicated in post‐stroke cognitive decline, yet the association with longitudinal changes in these markers remains unclear.

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.

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.

Post‐stroke IL‐6 trajectories associate with later cognition, highlighting potential therapeutic targets.

Rising interleukin (IL)‐6 by 6–9 months post‐ischemic stroke relates to worse long‐term cognition.This association is stronger than that seen with admission IL‐6 levels.Exploratory analyses suggest smoking and higher deprivation may drive elevated IL‐6.Smoking reduces Toll‐like receptor (TLR) signaling, strengthening a link with post‐stroke IL‐6 levels.Subacute circulating IL‐6 changes may predict or enable interventions for cognition.

Rising interleukin (IL)‐6 by 6–9 months post‐ischemic stroke relates to worse long‐term cognition.

This association is stronger than that seen with admission IL‐6 levels.

Exploratory analyses suggest smoking and higher deprivation may drive elevated IL‐6.

Smoking reduces Toll‐like receptor (TLR) signaling, strengthening a link with post‐stroke IL‐6 levels.

Subacute circulating IL‐6 changes may predict or enable interventions for cognition.