Dysfunction of the triple-network model is associated with cognitive impairment in patients with cerebral small vessel disease.

Purpose: This study aimed to demonstrate the correlations between the altered functional connectivity patterns in the triple-network model and cognitive impairment in patients with cerebral small vascular disease (CSVD). Methods: Resting-state functional magnetic resonance imaging data were obtained from 22 patients with CSVD and 20 healthy controls. The resting-state data were analyzed using independent component analysis and functional network connectivity (FNC) analysis to explore the functional alterations in the intrinsic triple-network model including the salience network (SN), default mode network (DMN), and central executive network (CEN), and their correlations with the cognitive deficits and clinical observations in the patients with CSVD. Results: Compared to the healthy controls, the patients with CSVD exhibited increased connectivity patterns in the CEN-DMN and decreased connectivity patterns in the DMN-SN, CEN-SN, intra-SN, and intra-DMN. Significant negative correlations were detected between the intra-DMN connectivity pattern and the Montreal Cognitive Assessment (MoCA) total scores (r = -0.460, p = 0.048) and MoCA abstraction scores (r = -0.565, p = 0.012), and a positive correlation was determined between the intra-SN connectivity pattern and the MoCA abstraction scores (r = 0.491, p = 0.033). Conclusions: Our study findings suggest that the functional alterations in the triple-network model are associated with the cognitive deficits in patients with CSVD and shed light on the importance of the triple-network model in the pathogenesis of CSVD.

Chronic gastritis may predict risk of cerebral small vessel disease.

BACKGROUND AND PURPOSE: Chronic gastritis, especially that caused by helicobacter pylori (HP) infection, has been associated with increased risk of ischemic stroke. But the relationship between chronic gastritis and cerebral small vessel disease (CSVD) remains largely undetermined. This study aimed to determine the potential predictors for CSVD, with chronic gastritis and its proxies as alternatives. METHOD: Patients aged 18 years or older with indications for electronic gastroscopy were enrolled. Presence of CSVD was evaluated with brain magnetic resonance imaging (MRI) results. Degree of CSVD was scored according to established criteria. Logistic regression analysis was used for identifying possible risk factors for CSVD. RESULTS: Of the 1191 enrolled patients, 757 (63.6%) were identified as with, and 434 (36.4%) as without CSVD. Multivariate analysis indicated that patients with chronic atrophic gastritis had an increased risk for CSVD than those without (adjusted odds ratio = 1.58; 95% CI, 1.08-2.32; P < 0.05). CONCLUSIONS: Chronic atrophic gastritis is associated with the presence of CSVD. We should routinely screen the presence of CSVD for patients with chronic atrophic gastritis.

HDL-C/LDL-C and Risk of Cerebral White Matter Hyperintensities: A Cross-Sectional Study.

Background and Purpose: At present, there is still a lack of metabolic indices to predict white matter hyperintensities. This study aimed to explore the correlations of the high-density lipoprotein cholesterol (HDL-C)/low-density lipoprotein cholesterol (LDL-C) ratio with the risk of white matter hyperintensities. Methods: Hospitalized patients who underwent inpatient treatment or physical examination due to various chronic diseases between January 18, 2018, and March 20, 2023, were enrolled. Fazekas scores were used to assess the severity of white matter hyperintensities. Logistic regression analysis was used to adjust for possible confounders. Results: Of the 1162 enrolled patients, 770 (66.27%) patients were classified as having no or mild WMHs, and 392 (33.73%) were classified as having moderate or severe WMHs. After adjusting for covariates, the logistic regression analysis indicated that the ratio of HDL-C to LDL-C was related to the severity of WMHs (Model 1, OR = 0.23, 95% CI: 0.07-0.73, P=0.012; Model 2, OR = 2.03, 95% CI: 1.12-3.67, P=0.019). Conclusion: Our findings suggest that the ratio of HDL-C to LDL-C is related to the severity of WMHs and that a high ratio of HDL-C to LDL-C is a protective factor against WMHs. This suggests that the ratio of HDL-C to LDL-C could be used as a metabolic prediction index of WMH severity.

Predicting the efficacy of non-steroidal anti-inflammatory drugs in migraine using deep learning and three-dimensional T1-weighted images.

Deep learning (DL) models based on individual images could contribute to tailored therapies and personalized treatment strategies. We aimed to construct a DL model using individual 3D structural images for predicting the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in migraine. A 3D convolutional neural network model was constructed, with ResNet18 as the classification backbone, to link structural images to predict the efficacy of NSAIDs. In total, 111 patients were included and allocated to the training and testing sets in a 4:1 ratio. The prediction accuracies of the ResNet34, ResNet50, ResNeXt50, DenseNet121, and 3D ResNet18 models were 0.65, 0.74, 0.65, 0.70, and 0.78, respectively. This model, based on individual 3D structural images, demonstrated better predictive performance in comparison to conventional models. Our study highlights the feasibility of the DL algorithm based on brain structural images and suggests that it can be applied to predict the efficacy of NSAIDs in migraine treatment.

Can Patients with Asymptomatic/Mild Illness and Moderate Illness COVID-19 Have White Matter Damage?

Background and Purpose: Studies have shown that severe coronavirus pandemic 2019 infection could lead to white matter hyperintensities, but the relationship between asymptomatic/mild illness and moderate illness coronavirus pandemic 2019 and white matter hyperintensities remains largely unknown. This study aimed to investigate the relationship between asymptomatic/mild illness and moderate illness coronavirus pandemic 2019 and the risk of white matter hyperintensities. Methods: Hospitalized patients who were confirmed to have coronavirus pandemic 2019 for the first time were enrolled. Fazekas scores were used for assessment of the severity of white matter hyperintensities. We also rated the 90-day functional outcome after discharge. Results: Of the 157 enrolled patients, 124 (78.98%) coronavirus pandemic 2019 patients were classified as having asymptomatic or mild illness, and 33 (21.02%) were classified as having moderate illness. The results showed that the Fazekas scale scores at baseline (periventricular white matter hyperintensities, 1.31±1.16 vs 2.06±1.20; Deep white matter hyperintensities, 1.04±0.97 vs 1.73±1.13 P <0.01) and at follow-up (periventricular white matter hyperintensities, 1.38±1.21 vs 2.09±1.21; Deep white matter hyperintensities, 1.13±1.04 vs 1.79±1.14 P <0.01) were lower in patients with symptomatic or mild illness than in those with moderate illness. Moreover, no significant difference (7.26% vs 3.03%; P =0.377) was observed between the two divided groups in terms of white matter hyperintensities progression. Conclusion: Our findings suggest that moderate COVID-19 is related to severe white matter hyperintensities compared with asymptomatic/mild illness but not to the progression of white matter hyperintensities.

CCL21/CCR7 axis regulates demyelination and vascular cognitive impairment in a mouse model for chronic cerebral hypoperfusion.

OBJECTIVES: White matter lesions (WML) are usually accompanied by cognitive decline, which consist of axonal loss and demyelination. CC chemokine ligand 21 (CCL21) and its receptor C-C chemokine receptor 7 (CCR7) belong to the chemokine family, which are involved in many diseases. However, their function in the central nervous system (CNS) is still unexplored. This study aimed to explore the role of CCL21/CCR7 axis in the pathological process of chronic ischemia-induced WML. METHODS: Bilateral common carotid artery stenosis (BCAS) was employed in C57BL/6 mice as the in vivo WML model. Microarray analysis was performed to detect the overall molecular changes induced in the endothelial cells by BCAS. Q-PCR, Western blotting, and immunofluorescence staining were performed to evaluate expression levels of the related molecules. The mice were injected with LV-CCL21-GFP virus in the corpus callosum to overexpress CCL21. WML degree was determined via MRI, and cognitive ability was assessed by Y-maze and novel object recognition tests. Myelin sheath integrity was evaluated via immunofluorescence staining. RESULTS: CCL21 was significantly downregulated in endothelial cells after BCAS and CCL21 overexpression alleviated BCAS-induced cognitive deficits and demyelination. Furthermore, CCR7 was found to be mainly expressed in oligodendrocytes (OLs) after exposed to hypoxia and CCR7 silencing blocked the protective effects induced by CCL21 overexpression. Conclusions CCL21/CCR7 axis may play a key role in demyelination induced by BCAS. This might provide a novel therapeutic target for WML.

Cerebral small vessel disease combined with cerebral collaterals to predict the prognosis of patients with acute large artery atherosclerotic stroke.

Background and purpose: Besides cerebral collaterals, few studies have examined other additional factors affecting the prognosis of patients with large artery atherosclerotic (LAA) stroke. Our study aims to explore the effect of the cerebral small vessel disease (SVD) and the effects of its interaction with cerebral collaterals on the prognosis of patients with acute LAA stroke. Method: Patients aged 18 years or older with LAA stroke within 24 h after stroke onset were consecutively enrolled. The functional outcome was determined using the modified Rankin Scale (mRS) at 3 months after stroke onset. Logistic multivariate analyses were used to identify the risk factors for stroke prognosis. Receiver operating characteristic (ROC) curves were constructed to compare the effects of cerebral collaterals and SVD on predicting the prognosis. Results: Of the 274 enrolled patients, 174 (63.50%) were identified as having a favorable prognosis, and 100 (36.50%) were identified as having an unfavorable prognosis. After adjusting for covariates, the logistic regression analysis identified that unfavorable prognosis was related to the total SVD score (Model 1, adjusted odds ratio = 1.73, 95% CI: 1.15-2.61, P < 0.01; Model 2, adjusted odds ratio = 1.85, 95% CI: 1.23-2.79, P < 0.01) and Tan score (Model 1, adjusted odds ratio = 0.38, 95% CI: 0.23-0.64, P < 0.01; Model 2, adjusted odds ratio = 0.52, 95% CI: 0.33-0.82, P < 0.01). Compared with cerebral collaterals (AUC = 0.59; 95% CI: 0.52-0.67; P < 0.01) or SVD (AUC = 0.62; 95% CI: 0.56-0.69; P < 0.01) alone, the combination of collaterals and SVD (AUC = 0.66; 95% CI: 0.59-0.73; P < 0.01) had higher diagnostic value for an unfavorable prognosis, and the optimal sensitivity and specificity were 77.01 and 53.00%, respectively. Conclusions: The total SVD burden was related to the prognosis of patients with LAA stroke. Compared with cerebral collaterals or SVD alone, cerebral collaterals combined with total SVD burden are better at predicting the prognosis of patients with acute LAA stroke.

Association Between White Matter Hyperintensities and Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Objectives: Previous studies of the associations between white matter hyperintensities (WMH) and chronic kidney disease (CKD) were still conflicting; therefore, our study aimed to conduct a systematic review of all of the available research on this topic and a meta-analysis of the association between WMH and CKD among observational studies. Setting and Design: Systematic review and meta-analysis. Outcome Measures: Severity of WMH. Methods and Participants: All relevant studies in public databases were examined until 15 November 2020. Two independent reviewers assessed all the included studies using the Cross-Sectional/Prevalence Study Quality (CSSQ) scale, and then literature review and meta-analyses were undertaken. Results: We pooled the odds ratio (OR) for the presence of WMH, periventricular hyperintensities (PVH), and deep subcortical white matter hyperintensities (DWMH) of patients with CKD vs. non-CKD patients by subgroup analysis, and the results obtained were WMH OR 2.07, 95% CI [1.58, 2.70], PVH OR 2.41, 95% CI [1.90, 3.05], and DWMH OR 2.11, 95% CI [1.60, 2.80], respectively. The main outcome showed that patients with CKD were more likely to have WMH in the brain compared to the normal controls. Another meta-analysis showed a statistically significant decline in renal function in patients with moderate to severe WMH compared with those with no to mild WMH. Conclusions: The findings indicated that patients with CKD were more likely to experience WMH than demographically matched controls. On the other hand, patients with moderate to severe WMH in the brain had poor renal function more frequently than those with no to mild WMH.

Can hyperuricemia predict the progression risk of cerebral small vessel disease?

AIMS: Uric acid (UA) may play a crucial role in the process of cerebral small vessel disease (SVD), but few follow-up studies have focused on the effect of UA in the progression of SVD. The present study aimed to ascertain whether serum UA levels are associated with the risk of SVD progression. METHODS: We performed an observational clinical study in adults older than 45 years with cranial magnetic resonance imaging (MRI) from 30 October 2015, to 28 January 2021. The patients were divided into two groups according to whether their total burden of SVD scores increased or not during the follow-up: SVD progression (increased by at least one point) and without SVD progression (increased 0 points). Cox regression and Kaplan-Meier survival analyses were used for univariate analysis between groups to identify the risk factors for SVD progression. RESULTS: Ultimately, 261 eligible patients were included in the final analysis. Of the 261 eligible patients, 73 were included in the SVD progression group, and 188 were included in the group without SVD progression. Correlation analysis found that the levels of UA and the ratio of hyperuricemia (HUA) showed statistically significant correlations with SVD progression risk (r = 0.197 and Crammer's V = 0.213, respectively, P < 0.01). Cox regression and Kaplan-Meier survival analyses showed that after adjustment for covariates, HUA was an independent risk factor for the incidence of SVD progression. The risk of SVD progression in patients with HUA was higher than that in those without HUA (HR (95% CI), 1.77 (1.03-3.05), P < 0.05). CONCLUSIONS: High serum UA levels are independently related to the risk of SVD progression, thus highlighting not only the influence of traditional risk factors such as hypertension and age on SVD but also the UA levels of patients for individualized treatment.

Association between small dense low-density lipoprotein cholesterol and neuroimaging markers of cerebral small vessel disease in middle-aged and elderly Chinese populations.

BACKGROUND: Cerebral small vascular disease (CSVD) is one of the leading causes of death in the aged population and is closely related to abnormalities in low-density lipoprotein cholesterol (LDL-C). Our study aims to clarify the relationship between small and dense low-density lipoprotein cholesterol (sdLDL-C) (a subcomponent of LDL-C) and neuroimaging markers of CSVD. METHODS: In total, 1211 Chinese adults aged ≥45 years with cranial magnetic resonance imaging (MRI) were recruited in this retrospective study from January 2018 to May 2021. Serum lipids and other baseline characteristics were investigated in relation to the occurrence of CSVD. A logistic regression model was performed to analyze the relationships between LDL subtypes and CSVD risk, and the Pearson correlation coefficient was used to analyze the correlation between clinical characteristics and CSVD risk. ROC curves and AUCs were created and depicted to predict the best cutoff value of LDL-C subtypes for CSVD risk. Based on these data, we performed comprehensive analyses to investigate the risk factors for CSVD. RESULTS: Ultimately, 623 eligible patients were included in the present study. Of the 623 eligible patients, 487 were included in the CSVD group, and 136 were included in the group without CSVD (control group). We adjusted for confounders in the multivariate logistic regression model, and LDL-C3 was still higher in the CSVD patients than in the group of those without CSVD (OR (95% CI), 1.22(1.08-1.38), P < 0.05). Pearson correlation showed that there was a positive correlation between the levels of LDL-C3, LDL-C4, LDL-C5, glucose, age, hypertension, previous ischemic stroke and CSVD risk (r > 0.15, P < 0.01). Moreover, the best cutoff value of LDL-C3 to predict CSVD was 9.5 mg/dL with 68.4% sensitivity and 72.8% specificity, and the best cutoff value of LDL-C4 to predict CSVD was 5.5 mg/dL with 50.5% sensitivity and 90.4% specificity. CONCLUSION: The results indicate that LDL-C3 is an independent risk factor for CSVD. A new prediction model based on LDL-C3 and LDL-C4 can help clinicians identify high-risk CSVD, even in people with normal LDL-C levels. The levels of sdLDL-C should be considered in the assessment and management of CSVD.

MCT2 overexpression promotes recovery of cognitive function by increasing mitochondrial biogenesis in a rat model of stroke.

Monocarboxylate transporter 2 (MCT2) is the predominant monocarboxylate transporter expressed by neurons. MCT2 plays an important role in brain energy metabolism. Stroke survivors are at high risk of cognitive impairment. We reported previously that stroke-induced cognitive impairment was related to impaired energy metabolism. In the present study, we report that cognitive function was impaired after stroke in rats. We found that MCT2 expression, but not that of MCT1 or MCT4, was markedly decreased in the rat hippocampus at 7 and 28 days after transient middle cerebral artery occlusion (tMCAO). Moreover, MCT2 overexpression promoted recovery of cognitive function after stroke. The molecular mechanism underlying these effects may be related to an increase in adenosine monophosphate-activated protein kinase-mediated mitochondrial biogenesis induced by overexpression of MCT2. Our findings suggest that MCT2 activation ameliorates cognitive impairment after stroke.

Validation of the Chinese version of Addenbrooke's Cognitive Examination III for diagnosing dementia.

OBJECTIVE: The aim of this study was to validate the reliability of the Chinese version of Addenbrooke's Cognitive Examination III (ACE-III) for detecting dementia. Furthermore, the present study compares the diagnostic accuracy of ACE-III with that of mini-mental state examination (MMSE). METHODS: One hundred seventy-seven patients with dementia and 180 healthy controls were included in the study. RESULTS: The reliability of ACE-III was very good (α-coefficient = 0.888). There was a significant negative correlation between Clinical Dementia Rating Scale score and total ACE-III score. Further, there was a positive correlation between MMSE score and total ACE-III score. Age exerted a significant effect on total ACE-III score, memory score, and language score. In the present study, the cutoff score of 83 showed a sensitivity of 91.1% and a specificity of 83.1%. CONCLUSIONS: The present findings support that the Chinese version of ACE-III is a reliable assessment tool for dementia. Copyright © 2017 John Wiley & Sons, Ltd.

[Evaluation and analysis of cognitive function in chronic renal failure patients].

OBJECTIVE: To explore the characteristics of cognitive impairment and correlation analysis in patients with chronic renal failure (CRF). METHODS: The Addenbrooke's cognitive examination revised (ACE-R) scale was used to evaluate the cognitive function for 101 cases of chronic renal failure patients (group CRF) receiving outpatient and inpatient treatments and selected 30 individuals with normal renal function as normal controls (group NC) for cross-sectional analysis. T test, receiver operating characteristic (ROC) curve and other statistical methods were adopted for comparing differences. RESULTS: (1) Compared with group NC (83.4 ± 6.5), group CRF (71.9 ± 17.6) showed significantly statistical difference on Addenbrooke's cognitive examination revised (ACE-R) scale scores (P < 0.01); (2)compared with normal controls, the patients with CRF had significantly statistical difference on the scores of visual spatial ability (11.5 ± 3.2, 14.0 ± 3.0 respectively), language fluency (7.0 ± 2.6, 8.7 ± 1.9) (P < 0.01) and memory (18.1 ± 7.0, 21.5 ± 3.6 respectively) (P < 0.05); (3) the cognitive function of patients with CRF were significantly positive correlated with glomerular filtration rate (GFR) (r = 0.614, P < 0.01) and negatively correlated with the duration of illness (r = -0.492, P < 0.01); (4) From ROC curve and the area under curve (AUC), ACE-R scale (AUC = 0.680) showed a higher sensitivity than mini-mental state examination scale (AUC = 0.576) in assessing cognitive function in patients with CRF (P < 0.01). CONCLUSION: (1) Under similar basic conditions of age, level of education and background, CRF patients showed significant damage overall cognitive function, cognitive impairment in visual spatial ability, executive function, long-term memory and logical judgment ability was particularly impaired. Immediate and delayed memory, attention, orientation and language ability also manifested different degrees of decline; (2) the severity of cognitive impairment in patients with CFR was closely related with the level of GFR; (3) the ACE-R scale showed a higher sensitivity than mini-mental state examination scale in assessing cognitive function in patients with CRF.