Unveiling the Inflammatory Predictors: Systemic Immune–Inflammation Index and Interleukin‐6 as Key Indicators of Early Poststroke Cognitive Decline

Background Systemic inflammation is a key contributor to poststroke cognitive impairment (PSCI) and subsequent poststroke dementia (PSD). This prospective cohort study evaluated the predictive efficacy of inflammatory markers for early PSCI/PSD and examined their associations with cognitive subdomains. Methods A total of 128 patients with acute cerebral infarction were categorized into PSCI ( n = 70) and non‐PSCI ( n = 58) groups; the PSCI group was further divided into PSD ( n = 43) and non‐PSD ( n = 27) subgroups. Blood levels of systemic immune–inflammation index (SII), high‐sensitivity C‐reactive protein (hs‐CRP), interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α) were measured within 24 h of admission. Logistic regression, receiver operating characteristic (ROC) curve analysis, DeLong test, and internal validation using 2000 bootstrap resamples were performed to assess model stability, with events per variable (EPV) and optimism values calculated. Correlation analyses were performed between biomarkers and Montreal Cognitive Assessment (MoCA) scores. Results PSCI patients had advanced age, lower education, and more severe stroke. SII, hs‐CRP, IL‐6, and TNF‐α rose in PSCI patients, with SII exhibiting the highest AUC among individual inflammatory markers (0.74). After joint adjustment for the four markers, only SII independently predicted PSCI (EPV = 5.39). Bootstrap showed that the SII‐based model had negligible overfitting, and the DeLong test found no AUC difference versus the four‐marker model ( p = 0.119). Within the PSCI cohort, only SII and IL‐6 increased in PSD patients (EPV = 7.17) and independently predicted PSD. Their combined model had the numerically highest AUC but no statistical superiority over single markers. Higher SII and IL‐6 levels correlated with worse global, memory, and visuospatial cognition. Conclusion After mutual adjustment for all inflammatory biomarkers, only SII independently predicted PSCI, while the combination of SII and IL‐6 emerged as an independent predictor of PSD. These findings do not negate the clinical utility of hs‐CRP, TNF‐α, and IL‐6 for evaluating systemic inflammatory status. The simplified SII‐based model achieved discriminative performance comparable to the full‐biomarker panel and provided a cost‐effective approach to facilitate tiered cognitive risk stratification following acute ischemic stroke.