ABSTRACT Aim To assess whether early plasma inflammatory proteins identify SVD‐related stroke patients at high risk of cognitive impairment and to examine imaging‐mediated effects. Methods This single‐center retrospective study (April 2020–August 2024) enrolled patients with MRI‐confirmed recent small subcortical infarct (RSSI) and healthy controls. GFAP and NLRP3 levels were measured by ELISA. MRI markers of small vessel disease—including white matter hyperintensities (WMH), lacunes, perivascular spaces, and microbleeds—were evaluated. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and functional outcome by the modified Rankin Scale (mRS) at 3 months. Associations were analyzed using correlation, regression, and mediation analyses. Results A total of 108 RSSI patients and 47 controls were included (mean age 57.9 ± 10.5 years; 64.1% male). RSSI patients had significantly higher plasma GFAP and NLRP3 levels ( p < 0.05). Both proteins were inversely associated with total MoCA scores and cognitive subdomains, but not with 3‐month mRS. GFAP and NLRP3 correlated positively with periventricular WMH (PWMH). Mediation analysis showed that PWMH accounted for 23.88%–28.10% of the association between plasma protein levels and cognitive impairment. Conclusions Elevated plasma GFAP and NLRP3 are associated with post‐stroke cognitive impairment in RSSI, partially mediated by PWMH. These biomarkers may help identify patients at risk of early cognitive decline.
Lan et al. (Sun,) studied this question.