ORIGINAL RESEARCH article
Front. Hum. Neurosci.
Sec. Brain Imaging and Stimulation
Volume 19 - 2025 | doi: 10.3389/fnhum.2025.1673301
This article is part of the Research TopicAdvances in neuroimaging, genetic, and stimulation methods for cognitive and behavioral function investigationView all articles
Enlarged perivascular spaces in the basal ganglia mediate the negative impact of HbA1c levels on mild cognitive impairment
Provisionally accepted
- 1Department of Neurology, The Third Hospital of Hebei Medical University, Shijiazhuang, China
- 2Department of Neurology, Peking University People's Hospital, Beijing, China
- 3Hebei Medical University, Shijiazhuang, China
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Background This study aimed to investigate the mediating effect of enlarged perivascular space (EPVS) in basal ganglia (BG) on the relationship between glycated hemoglobin (HbA1c) levels and mild cognitive impairment(MCI)in patients with cerebral small vessel disease (CSVD) . Methods Data on HbA1c levels and MOCA scores and CSVD imaging markers, including EPVS volume and distribution patterns were collected. Logistic regression was performed to identify independent risk factors for MCI. A mediation effect analysis was further conducted to determine whether BG-EPVS mediate the impact of HbA1c on cognitive impairment. Results A total of 244 CSVD patients were enrolled in this study.Compared with non-DM patients, DM patients had a significantly greater BG-EPVS volume (P<0.001) and more severe periventricular white matter hyperintensities (p-WMH) (P=0.036). Multivariate logistic regression analysis revealed that hypertension [odds ratio (OR)=3.823; 95% confidence interval (CI):1.707-8.566; P=0.001], the HbA1c level(OR=1.689; 95%CI:1.255-2.272; P<0.001) and BG-EPVS volume (OR=1.001; 95% CI:1.000-1.003; P=0.038) were independent risk factors for MCI. After adjusting for sex and age, partial correlation analysis revealed a significant positive correlation between BG-EPVS volume and HbA1c (β=0.137; P=0.042) and a significant negative correlation with MOCA scores (β=−0.160; P=0.013). The effect of HbA1c on MCI in patients with CSVD was indirectly mediated by BG-EPVS volume (Indirect effect=-0.074; 95% CI: -0.187 to -0.012; The mediating effect ratio was 11.3%). Conclusion HbA1c is an independent risk factor for MCI. Increased BG-EPVS volume mediates the partial effect of HbA1c on CSVD-related cognitive dysfunction.
Keywords: enlarged perivascular spaces, Cerebral small vessel disease, glycatedhemoglobin, Diabetes Mellitus, Mild Cognitive Impairment
Received: 25 Jul 2025; Accepted: 01 Oct 2025.
Copyright: © 2025 Liu, Liu, Yang, Xu, Li, Wang, Ren and Liu. 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: Junyan Liu, 36300351@hebmu.edu.cn
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