Mediation analysis showed that PWMH accounted for 23.88%-28.10% of the association between plasma protein levels and cognitive impairment.<h4>Conclusions</h4>Elevated plasma GFAP and NLRP3 are associated with post-stroke cognitive impairment in RSSI, partially mediated by PWMH. The gene discussed is NLRP3; the disease is Cognitive impairment.