Low Serum Superoxide Dismutase Is Associated With a High Risk of Cognitive Impairment After Mild Acute Ischemic Stroke

Ming-Si Zhang; Jian-Hai Liang; Meng-Jia Yang; Yue-Ran Ren; Dai-Hong Cheng; Qi-Heng Wu; Yan He; Jia Yin

doi:10.3389/fnagi.2022.834114

Low Serum Superoxide Dismutase Is Associated With a High Risk of Cognitive Impairment After Mild Acute Ischemic Stroke

Front Aging Neurosci. 2022 Feb 28:14:834114. doi: 10.3389/fnagi.2022.834114. eCollection 2022.

Authors

Ming-Si Zhang¹, Jian-Hai Liang¹, Meng-Jia Yang¹, Yue-Ran Ren¹, Dai-Hong Cheng¹, Qi-Heng Wu¹, Yan He², Jia Yin¹

Affiliations

¹ Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
² Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medicine University, Guangzhou, China.

Abstract

Background: Post-stroke cognitive impairment (PSCI) is a common complication after stroke, but effective therapy is limited. Identifying potential risk factors for effective intervention is warranted. We investigated whether serum superoxide dismutase (SOD) levels were related to cognitive impairment after mild acute ischemic stroke (AIS) by using a prospective cohort design.

Methods: A total of 187 patients diagnosed with mild AIS (National Institutes of Health Stroke Scale ≤ 8) were recruited. Serum SOD, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6) levels were measured, and cognitive assessments (Mini-Mental State Examination, MMSE; Montreal Cognitive Assessment, MoCA) were performed in the early phase (within 2 weeks). These indexes and assessments were repeated at 3 months after onset. MoCA < 22 was defined as early cognitive impairment (CI-E) within 2 weeks and late cognitive impairment (CI-L) at 3 months after stroke.

Results: In a survey, 105 of 187 (56.1%) patients were identified as CI-E after mild AIS. Lower serum SOD associated with higher inflammatory biomarkers (ESR, CRP, and IL-6) and worse cognitive scores was observed in CI-E patients. In a survey, 39 of 103 (37.9%) stroke patients who completed the 3-month follow-up were identified as CI-L. Serum SOD was consistently lower in CI-L patients at baseline and 3 months and positively associated with cognitive scores. In adjusted analyses, low serum SOD at baseline was independently associated with high risks of CI-E and CI-L, with odds ratios (ORs) of 0.64 and 0.33 per standard deviation increase in serum SOD, respectively. Multiple-adjusted spline regression models showed linear associations between serum SOD and CI-E (P = 0.044 for linearity) and CI-L (P = 0.006 for linearity). Moreover, 35.2% (19/54) of CI-E patients cognitively recovered during the 3-month follow-up. In multivariable analysis, SOD was identified as a protective factor for cognitive recovery after stroke (OR 1.04, 95% CI: 1.01-1.08, P = 0.024).

Conclusion: We demonstrate that low serum SOD is associated with a high risk of cognitive impairment after mild AIS, indicating SOD may be a potential modifiable factor for PSCI.

Keywords: MMSE; MoCA; cognitive impairment (CI); ischemic stroke; superoxide dismutase.