Accurate identification of high-risk vulnerable plaques and assessment of stroke risk are crucial for clinical decision-making, yet reliable non-invasive predictive tools are currently lacking. This study aimed to develop an artificial intelligence model based on high-resolution vessel wall imaging (HR-VWI) to assist in the identification of vulnerable plaques and prediction of stroke recurrence risk in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). Between June 2018 and June 2024, a retrospective collection of HR-VWI images from 1806 plaques in 726 sICAS patients across four medical institutions was conducted. K-means clustering was applied to the T1-weighted imaging (T1WI) and T1-weighted imaging with contrast enhancement (T1CE) sequences. Following feature extraction and selection, radiomic models and habitat models were constructed. Additionally, the Vision Transformer (ViT) architecture was utilized for HR-VWI image analysis to build a deep learning model. A stacking fusion strategy was employed to integrate the habitat model and ViT model, enabling effective identification of high-risk vulnerable plaques in the intracranial region and prediction of stroke recurrence risk. Model performance was evaluated using receiver operating characteristic (ROC) curves, and model comparisons were conducted using the DeLong test. Furthermore, decision curve analysis and calibration curves were utilized to assess the practicality and clinical value of the model. The fused Habitat + ViT model exhibited excellent performance in both the validation and test sets. In the validation set, the model achieved an area under the curve (AUC) of 0.949 (95% CI: 0.927–0.969), with a sensitivity of 0.879 (95% CI: 0.840–0.945), a specificity of 0.905 (95% CI: 0.842–0.949), and an accuracy of 0.897 (95% CI: 0.870–0.926). In the test set, the AUC increased to 0.960 (95% CI: 0.941–0.973), with specificity rising to 0.963 and an accuracy of 0.885 (95% CI: 0.857–0.913). The DeLong test revealed statistically significant differences in AUC between the fused model and the single-modal models (test set, vs. ViT p = 0.000; vs. Habitat p = 0.000) Cox regression analysis showed that the Habitat + ViT index, based on the prediction probability of the Habitat + ViT model, was an independent predictor of stroke recurrence (HR: 2.07; 95% CI: 1.12–3.81), with significant predictive power for stroke events at multiple time points. Specifically, measured by AUC values, the model’s predictive performance at 1, 2, 3, and 4 years was 0.751 (95% CI: 0.679–0.823), 0.820 (95% CI: 0.760–0.876), 0.815 (95% CI: 0.753–0.877), and 0.780 (95% CI: 0.680–0.873), respectively. The integrated Habitat + ViT model based on HR-VWI demonstrated superior performance in identifying high-risk vulnerable plaques in sICAS patients and predicting stroke recurrence risk, providing valuable support for clinical decision-making. This study was supported by the 10.13039/501100001809 National Natural Science Foundation of China (grant 82204933). Henan Key Laboratory of Neurorestoratology (HNSJXF-2021-004), 2019 Joint Construction Project of Henan Provincial Health Committee and Ministry of Health (SB201901061), and the Xin Xiang City Acute Ischemic Stroke Precision Prevention and Treatment Key Laboratory.

To investigate the correlation and predictive value of serum matrix metalloproteinase-9 (MMP-9) level with cognitive dysfunction and total imaging load in patients with cerebral small vessel disease (CSVD). A total of 80 patients with CSVD who were admitted to the First Affiliated Hospital of Xinxiang Medical University between April 2019 and April 2020 were enrolled. All subjects underwent T1-weighted imaging (T1WI), T2WI, fluid-attenuated inversion recovery (FLAIR), diffusion weighted imaging (DWI), serum sample collection, and assessment of cognitive function at a specific time-point after admission. According to the results of the neuropsychological test, subjects were divided into cognitive dysfunction group (n=40) and normal cognitive function group (n=40). The total imaging load was estimated according to the neuroimaging findings. Serum MMP-9 level was measured by an enzyme-linked immunosorbent assay (ELISA) kit. Beside, serum MMP-9 level and total imaging load were compared between the two groups. Serum levels of MMP-9 and plasma total homocysteine (tHcy) were negatively correlated with cognitive function (P<0.05). Serum MMP-9 level was found as a significant factor for diagnosing cognitive impairment due to CSVD (area under the curve (AUC), 0.756; sensitivity and specificity were 97.5% and 75.0%, respectively). THcy level was also found as significant factor for diagnosing cognitive impairment due to CSVD (area under the curve (AUC), 0.727; sensitivity and specificity were 97.5% and 75.0%, respectively). Serum MMP-9 level and tHcy level were significantly correlated with cognitive function in patients with CSVD. Serum MMP-9 level has a specific correlation with the total imaging load in patients with CSVD. It plays an important role in diagnosing cognitive impairment in patients with CSVD.

Background: Matrix metalloproteinase-9 (MMP-9) is a significant protease required for synaptic plasticity, learning, and memory. Yet, the role of MMP-9 in the occurrence and development of cognitive decline after ischemic stroke is not fully understood. In this study, we used clinical data experiments to further investigate whether MMP-9 and genetic polymorphism are associated with post-stroke cognitive impairment or dementia (PSCID). Materials and Methods: A total of 148 patients with PSCID confirmed by the Montreal Cognitive Assessment (MoCA) 3 months after onset (PSCID group) were included in the study. The MMP-9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism, and the serum level of MMP-9 was measured using enzyme-linked immunosorbent assay (ELISA). The same manipulations have been done on 169 ischemic stroke patients without cognitive impairment (NCI group) and 150 normal controls (NC group). Results: The expression level of serum MMP-9 in the PSCID group and NCI group was higher compared to the NC group, and the levels in the PSCID group were higher than that in the NCI group (all p <math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="w1" alttext=" < 0.05). Diabetes mellitus, hyperhomocysteinemia, and increased serum MMP-9 levels were the main risk factors of cognitive impairment after ischemic stroke. The serum level of MMP-9 was negatively correlated with the MoCA score, including visual-spatial executive, naming, attention, language, and delayed recall. Genetic polymorphism showed that TC genotype with MMP-9 rs3918242 and CC genotype were associated with a significantly increased risk of PSCID; moreover, the TC genotype significantly increased the risk of cognitive impairment. In the TCCC genotype of MMP-9 rs3918242, diabetes mellitus and hyperhomocysteinemia were associated with the increased risk of PSCID; also, hyperhomocysteinemia could increase the risk of cognitive impairment. Conclusions: MMP-9 level and MMP-9 rs3918242 polymorphism have an important role in the occurrence and development of post-stroke cognitive impairment or dementia (PSCID).

Cerebral small vascular disease (CSVD) is a common type of cerebrovascular disease, and an important cause of vascular cognitive impairment (VCI) and stroke. The disease burden is expected to increase further as a result of population aging, an ongoing high prevalence of risk factors (e.g., hypertension), and inadequate management. Due to the poor understanding of pathophysiology in CSVD, there is no effective preventive or therapeutic approach for CSVD. Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that is related to the occurrence and development of vascular dysfunction diseases. Therefore, MIF may contribute to the pathogenesis of CSVD and VCI. Here, reviewed MIF participation in chronic cerebral ischemia-hypoperfusion and neurodegeneration pathology, including new evidence for CSVD, and its potential role in protection against VCI.

Objectives: To investigate the correlation between serum angiopoietin‐like protein 4 (ANGPTL4) levels, white matter hyperintensity (WMH), and cognitive impairment (CI) in patients with cerebral small vessel disease (CSVD).Methods: This cross‐sectional study enrolled 171 patients with CSVD who attended the First Affiliated Hospital of Xinxiang Medical University from December 2021 to July 2022. All subjects underwent a 3.0T head magnetic resonance imaging, neuropsychology assessment, and blood sampling. Serum ANGPTL4 levels were detected by enzyme‐linked immunosorbent assay and the severity of WMH was assessed by the Fazekas scale. According to the Montreal Cognitive Assessment (MoCA) scale, subjects were divided into normal cognition group (NC, n = 80) and CI group (n = 91). According to the total Fazekas scores, subjects were divided into a mild WMH group (n = 84), a moderate WMH group (n = 70), and a severe WMH group (n = 17).Results: Serum ANGPTL4 levels were significantly higher in the CI group than in the NC group (p < .05) and were negatively correlated with mini–mental state examination scores and MoCA scores (r = −0.26, −0.341, p < .05). Serum ANGPTL4 levels increased significantly in the mild to moderate WMH group but tended to decrease in the severe WMH group. Binary logistic regression analysis showed that ANGPTL4 was an independent influencing factor for CSVD‐CI (OR = 2.062, 95% CI (1.591–2.674), p < .001). The area under curve of ANGPTL4 for CSVD‐CI was 0.847 (0.791–0.903).Conclusion: ANGPTL4 may be involved in the process of white matter damage and CI in CSVD patients and shows a diagnostic value for CSVD‐CI.

C-X3-C motif chemokine ligand 1 (CX3CL1), a structurally unique chemokine in the central nervous system (CNS), shapes physiological and pathological processes via specific binding to its receptor, C-X3-C motif chemokine receptor 1 (CX3CR1). Empirical evidence indicates that this signaling axis exerts dual neuroinflammatory effects: It restrains microglial hyperactivation, yet can promote inflammation under conditions such as chronic stress. Notably, it preserves synaptic plasticity and facilitates remyelination. Age-associated reductions in CX3CL1 exhibit a strong correlation with cognitive decline; administration of exogenous CX3CL1 partially mitigates these deficits. This study provides a comprehensive account of the multifaceted functions and regulatory mechanisms of CX3CL1 in CNS diseases, thereby establishing a basis for potential new therapeutic targets.