The correlation between the severity of cerebral microbleeds and serum HMGB1 levels and cognitive impairment in patients with cerebral small vessel disease

Minghua Wang; Junli Liu; Fan Wang; Qing Li; Jian Zhang; Sibei Ji; Shaomin Li; Chengbiao Lu; Jianhua Zhao

doi:10.3389/fnagi.2023.1221548

The correlation between the severity of cerebral microbleeds and serum HMGB1 levels and cognitive impairment in patients with cerebral small vessel disease

Front Aging Neurosci. 2023 Jun 22:15:1221548. doi: 10.3389/fnagi.2023.1221548. eCollection 2023.

Authors

Minghua Wang¹, Junli Liu¹, Fan Wang¹, Qing Li¹, Jian Zhang², Sibei Ji¹, Shaomin Li³, Chengbiao Lu⁴, Jianhua Zhao¹

Affiliations

¹ Henan Joint International Research Laboratory of Neurorestoratology for Senile Dementia, Henan Key Laboratory of Neurorestoratology, Neurology, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
² Imaging Department, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
³ Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
⁴ Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province, Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, China.

Abstract

Objective: The study investigated the correlation and predictive value between the severity of cerebral microbleeds (CMBs) and the level of serum High Mobility Group Protein B1 (HMGB1) and the occurrence of cognitive impairment in patients with cerebral small vessel disease (CSVD).

Methods: A total of 139 patients with CSVD admitted to the Department of Neurology of the First Affiliated Hospital of Xinxiang Medical University from December 2020 to December 2022 were selected as study subjects. The Montreal Cognitive Assessment (MoCA) scale was used to assess the cognitive function and was divided into the cognitive impairment group and the cognitive normal group. Magnetic Resonance Imaging (MRI) and Susceptibility Weighted Imaging (SWI) were used to screen and assess the severity of CMBs. Serum HMGB1 levels of CSVD patients were measured by enzyme linked immunosorbent assay (ELISA). Multivariable logistic regression analysis was used to explore risk factors for cognitive impairment and CMBs. Pearson correlation analysis was used to investigate the correlation between HMGB1 and cognitive function. Receiver Operating Characteristics (ROC) curves were used to assess the predictive value of HMGB1 for the occurrence of cognitive impairment in patients with CMBs.

Results: High Mobility Group Protein B1, uric acid (UA), glycosylated hemoglobin (HbA1c), CMBs, lacunar cerebral infarction (LI), years of education, and history of hypertension were risk factors for cognitive impairment (P < 0.05); HMGB1 was significantly and negatively associated with total MoCA score, visuospatial/executive ability, and delayed recall ability (P < 0.05). HMGB1 was significantly and positively correlated with the number of CMBs (P < 0.05). The area under the ROC curve for HMGB1 predicting cognitive impairment in patients with CMBs was 0.807 (P < 0.001).

Conclusion: Serum HMGB1 levels are associated with the development of cognitive impairment in CSVD patients, and serum HMGB1 levels have a high predictive value for the development of cognitive impairment in CSVD patients with combined CMBs, which can be used for early clinical identification and intervention of vascular cognitive impairment.

Keywords: HMGB1; blood-brain barrier; cerebral microbleeds; cerebral small vessel disease; cognitive.

Grants and funding

This study was supported by the National Natural Science Foundation of China (81771517), Natural Science Foundation of Henan Province (182300410389); Joint Construction Project of Henan Medical Science and Technology Project (LHGJ20190437); Xinxiang Medical University Scientific Research Innovation Support Program Project (YJSCX202185Y); and Henan Province Science and Technology, Department of Science and Technology Tackling Program International Cooperation Project (232102521029).