ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Neurodegeneration
Superoxide dismutase is associated with cerebral small vessel disease burden and vascular mild cognitive impairment in elderly patients
Provisionally accepted
Xiaohua Xie
Meixi LiTianyuan Guan
Zhenjie Teng
Jing FengJing XuQianqian Qi
Yining Xiao
Peiyuan Lv
Yanhong Dong*- Hebei General Hospital Affiliated to Hebei Medicine University, Shijiazhuang, China
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Objective: To examine the associations between superoxide dismutase (SOD) levels and the burden of cerebral small vessel disease (CSVD), as well as vascular mild cognitive impairment (VaMCI), in elderly patients. Methods: In this study, a cohort of 286 elderly individuals was included. Each participant received a comprehensive cognitive assessment. Plasma SOD levels were evaluated. The cumulative CSVD burden was quantified using an ordinal scale ranging from 0 to 4, based on four key imaging indicators of CSVD: white matter hyperintensity, deep cerebral microbleeds, lacunes, and enlarged perivascular spaces in the basal ganglia. To evaluate the associations among SOD levels, CSVD burden, and cognitive function, we employed binary logistic regression analysis, tests for trend, receiver operating characteristic curve analysis, and mediation analysis. Results: After adjusting for potential confounders, multivariate logistic regression analysis revealed that elevated levels of SOD were significantly associated with a reduced risk of VaMCI (OR: 0.919 ; 95% CI: 0.896 to 0.943; P < 0.001) and a lower likelihood of severe CSVD burden (OR: 0.980; 95% CI: 0.968 to 0.992; P = 0.001) in elderly patients. Compared with the lowest quartile of SOD levels, the OR for VaMCI in the highest quartile of SOD levels was 0.039 (95% CI: 0.016 to 0.100; P for trend <0.001) after adjusting for potential confounders. For severe CSVD burden, the corresponding OR was 0.442 (95% CI: 0.214-0.913; P for trend = 0.011). Mediation analysis revealed that the severe CSVD burden significantly moderated the relationship between SOD levels and VaMCI. Conclusions: Elevated SOD levels serve as a protective factor against severe CSVD burden and VaMCI in elderly patients. A portion of the protective effect of increased SOD on VaMCI may be attributed to its role in mitigating the severity of CSVD.
Keywords: Cerebral small vessel disease, Mild Cognitive Impairment, Oxidative Stress, Superoxide Dismutase, vascular cognitive impairment
Received: 21 Oct 2025; Accepted: 09 Dec 2025.
Copyright: © 2025 Xie, Li, Guan, Teng, Feng, Xu, Qi, Xiao, Lv and Dong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yanhong Dong
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