Objective To explore the correlations of serum heat shock protein 70 (Hsp70), high-mobility group box 1 (HMGB1), glial fibrillary acidic protein (GFAP), and cognitive impairment (CI) in patients with cerebral small vessel disease (CSVD).

Methods A total of 117 patients with CSVD who were treated at Kailuan General Hospital from July 2023 to July 2024 were selected as study subjects (CSVD group). According to varied scores of the Mini-Mental State Examination (MMSE), they were divided into CI group (54 cases) and non-CI group (63 cases). Additionally, 120 healthy individuals who underwent health check-ups during the same period were selected as control group. Clinical data of all subjects were collected. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of Hsp70, HMGB1, and GFAP in serum. The Spearman method was employed to analyze the correlations of serum Hsp70, HMGB1, and GFAP levels with the occurrence of CI in CSVD patients. Logistic multivariate regression analysis was conducted to screen for influencing factors of CI in CSVD patients. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum Hsp70, HMGB1, and GFAP levels for CI in CSVD patients.

Results The serum levels of Hsp70, HMGB1, and GFAP in the CSVD group were higher than those in the control group (P < 0.05). There were no significant differences in gender, age, body mass index, smoking history, drinking history, nature of CSVD, education level, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), Trail Making Test-A (TMT-A), Trail Making Test-B (TMT-B), and low-density lipoprotein cholesterol (LDL-C) between the CI group and the non-CI group (P>0.05). The levels of uric acid (UA), serum Hsp70, HMGB1, and GFAP in the CI group were higher than those in the non-CI group, while the Montreal Cognitive Assessment (MOCA) score was lower than that in the non-CI group (P < 0.05). The serum levels of Hsp70, HMGB1, and GFAP in CSVD patients were negatively correlated with MMSE scores (r=-0.458, -0.525, -0.431, P < 0.05) and MOCA scores (r=-0.462, -0.583, -0.484, P < 0.05). Logistic regression analysis showed that Hsp70, HMGB1, and GFAP were influencing factors for CI in CSVD patients (P < 0.05). The areas under the curve (AUC) for serum Hsp70, HMGB1, and GFAP levels and their combined prediction of cognitive function in CSVD patients were 0.734, 0.769, 0.766, and 0.902, respectively. The predictive efficacy of the combined prediction was better than that of individual indicators (P < 0.05).

Conclusion The serum levels of Hsp70, HMGB1, and GFAP are elevated in CSVD patients, which are closely related to the occurrence of CI. The combined detection of these three proteins has a high predictive value for CI in CSVD patients.