Systemic Immune-Inflammation Index is Associated with Cerebral Small Vessel Disease Burden and Cognitive Impairment

Yining Xiao,1– 3 Zhenjie Teng,1– 3 Jing Xu,2,3 Qianqian Qi,2 Tianyuan Guan,1,2 Xin Jiang,2,3 Huifang Chen,2 Xiaohua Xie,2 Yanhong Dong,2,3 Peiyuan Lv1– 3 1Department of Neurology, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Hebei Provincial Key Laboratory of Cerebral Networks and Cognitive Disorders, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Peiyuan Lv, Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email peiyuanlu2@163.comObjective: This study sought to explore the associations of the systemic immune-inflammation index (SII) with total cerebral small vessel disease (CSVD) burden and cognitive impairment.Methods: We enrolled 201 patients in the retrospective study with complete clinical and laboratory data. The SII was calculated as platelet count × neutrophil count/lymphocyte count. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Total CSVD burden was assessed based on magnetic resonance imaging. We performed logistic regression models, Spearman correlation, and mediation analysis to evaluate the associations of SII with CSVD burden and cognitive impairment.Results: After adjustment for confounding factors in the multivariate binary logistic regression model, elevated SII (odds ratio [OR], 3.263; 95% confidence interval [CI], 1.577– 6.752; P = 0.001) or severe CSVD burden (OR, 2.794; 95% CI, 1.342– 5.817; P = 0.006) was significantly associated with the risk of cognitive impairment. Correlation analyses revealed that SII levels were negatively associated with MMSE scores (rs = − 0.391, P < 0.001), and positively associated with the total CSVD burden score (rs = 0.361, P < 0.001). Moreover, SII was significantly related to the severity of the CSVD burden (OR, 2.674; 95% CI, 1.359– 5.263; P = 0.004). The multivariable-adjusted odds ratios (95% CI) in highest tertile versus lowest tertile of SII were 8.947 (3.315– 24.145) for cognitive impairment and 4.945 (2.063– 11.854) for severe CSVD burden, respectively. The effect of higher SII on cognitive impairment development was partly mediated by severe CSVD burden.Conclusion: Elevated SII is associated with severe CSVD burden and cognitive impairment. The mediating role of severe CSVD burden suggests that higher SII may contribute to cognitive impairment through aggravating CSVD burden.Keywords: systemic immune-inflammation index, inflammation, cognitive impairment, cerebral small vessel disease, total burden