Inflammation, Anti-inflammatory Interventions, and Post-stroke Cognitive Impairment: a Systematic Review and Meta-analysis of Human and Animal Studies

The pathophysiology and treatment of post-stroke cognitive impairment (PSCI) are not clear. Stroke triggers an inflammatory response, which might affect synapse function and cognitive status. We performed a systematic review and meta-analysis to assess whether patients with PSCI have increased levels of inflammatory markers and whether anti-inflammatory interventions in animals decrease PSCI. We systematically searched PubMed, EMBASE, and PsychInfo for studies on stroke. For human studies, we determined the standardized mean difference (SMD) on the association between PSCI and markers of inflammation. For animal studies, we determined the SMD of post-stroke cognitive outcome after an anti-inflammatory intervention. Interventions were grouped based on proposed mechanism of action. In patients, the SMD of inflammatory markers for those with versus those without PSCI was 0.46 (95% CI 0.18; 0.76; I 2  = 92%), and the correlation coefficient between level of inflammation and cognitive scores was - 0.25 (95% CI - 0.34; - 0.16; I 2  = 75%). In animals, the SMD of cognition for those treated with versus those without anti-inflammatory interventions was 1.43 (95% CI 1.12; 1.74; I 2  = 83%). The largest effect sizes in treated animals were for complement inhibition (SMD = 1.94 (95% CI 1.50; 2.37), I 2  = 51%) and fingolimod (SMD = 2.1 (95% CI 0.75; 3.47), I 2  = 81%). Inflammation is increased in stroke survivors with cognitive impairment and is negatively correlated with cognitive functioning. Anti-inflammatory interventions seem to improve cognitive functioning in animals. Complement inhibition and fingolimod are promising therapies on reducing PSCI.