A Nomogram Including Total Cerebral Small Vessel Disease Burden Score for Predicting Mild Vascular Cognitive Impairment in Patients with Type 2 Diabetes Mellitus.

Background: Total cerebral small vessel disease (CSVD) burden score is an important predictor of vascular cognitive impairment (VCI). However, few predictive models of VCI in type 2 diabetes mellitus (T2DM) patients have included the total CSVD burden score, especially in the early stage of VCI. Objective: To develop and validate a nomogram that includes the total CSVD burden score to predict mild VCI in patients with T2DM. Methods: A total of 322 eligible participants with T2DM who were divided into mild and normal cognitive groups were enrolled in this retrospective study. Demographic data, laboratory data and imaging markers of CSVD were collected. The total CSVD burden score was calculated by combining the different CSVD markers. Step-backward multivariable logistic regression analysis with the Akaike information criterion was applied to select significant predictors and develop a best-fit predictive nomogram. The performance of the nomogram was assessed in terms of discriminative ability, calibrated ability, and clinical usefulness. Results: The nomogram model consisted of five variables: age, education, hemoglobin A1c level, serum homocysteine level, and total CSVD burden score. A nomogram with these variables showed good discriminative ability (area under the receiver operating characteristic curve was 0.801 in internal verification). In addition, the Hosmer-Lemeshow test (χ2 =9.226, P=0.417) and bootstrap-corrected calibration plot indicated that the nomogram had good calibration. The Brier score of the predictive model was 0.178. Decision curve analysis demonstrated that when the threshold probability ranged between 16% and 98%, the use of the nomogram to predict mild VCI in patients with T2DM provide a greater net benefit. Conclusions: The nomogram, composed of age, education, stroke, HbA1c level, Hcy level, and total CSVD burden score, had good predictive accuracy and may provide clinicians with a practical tool for predicting the risk of mild VCI in T2DM patients.

Association of triglyceride-glucose index with major depressive disorder: A cross-sectional study.

The triglyceride-glucose (TyG) index has been proposed as a new marker for insulin resistance, which is associated with a risk of major depressive disorder (MDD). This study aims to explore whether the TyG index is correlated with MDD. In total, 321 patients with MDD and 325 non-MDD patients were included in the study. The presence of MDD was identified by trained clinical psychiatrists using the International Classification of Diseases 10th Revision. The TyG index was calculated as follows: Ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The results revealed that the MDD group presented higher TyG index values than the non-MDD group (8.77 [8.34-9.17] vs 8.62 [8.18-9.01], P < .001). We also found significantly higher morbidity of MDD in the highest TyG index group than in the lower TyG index group (59.9% vs 41.4%, P < .001). Binary logistic regression revealed that TyG was an independent risk factor for MDD (odds ratio [OR] 1.750, 95% confidence interval: 1.284-2.384, P < .001). We further assessed the effect of TyG on depression in sex subgroups. The OR was 3.872 (OR 2.014, 95% confidence interval: 1.282-3.164, P = .002) for the subgroup of men. It is suggested that the TyG index could be closely associated with morbidity in MDD patients; thus, it may be a valuable marker for identifying MDD.

Gender heterogeneity in the influencing factors for cerebral microbleeds in acute ischemic stroke patients.

BACKGROUND: Cerebral microbleeds (CMBs) are common in acute ischemic stroke (AIS) patients. The presence of CMBs increases the risk of hemorrhagic transformation in AIS patients, and it is also closely associated with cognitive decline and even dementia. At present, there exist different opinions on the independent risk factors for CMBs, and there is no consensus on whether there are gender differences in -post-stroke CMB. Therefore, this study sought to investigate gender heterogeneity in the influencing factors for CMBs by studying male and female AIS patients. METHODS: This was a China-based, Single-center, retrospective review of data from 482 AIS inpatients at the Neurology Department of Hebei General Hospital (NCT05882123). Both demographic and clinical data were collected from the study subjects. Different head magnetic resonance imaging sequences were used to assess the subjects' CMBs, white matter lesions, and old lacunar infarcts (LI). Various statistical methods, including the t-test, χ2 test, and logistic regression, were used to analyze the gender heterogeneity of the influencing factors for CMBs in AIS patients. RESULTS: When compared with the male AIS patients, the female AIS patients were older and had higher total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, ApoA, ApoB, and fibrinogen levels. The female AIS patients also had higher National Institute of Health Stroke Scale scores and hypertension disease composition ratios. By contrast, the proportions of female AIS patients with a history of smoking and a history of alcohol consumption were both lower than the corresponding proportions of male AIS patients. These differences were all statistically significant (p < .05). There were no statistically significant differences in the incidence and severity of CMBs between the male and female AIS patients (χ2 ＝ 0.851, 3.092, p > .05). The univariate and multivariate stepwise logistic regression analyses confirmed that age (OR = 1.074, 95% CI: 1.013-1.139, p = .016) and old LI (OR = 4.295, 95% CI: 1.062-17.375, p = .041) were independent risk factors for comorbid CMBs in the female AIS patients, while blood glucose (OR = 0.692, 95% CI: 0.494-0.968, p = .031) was an independent protective factor for comorbid CMBs in the female AIS patients. However, these factors were not found to be independent risk or protective factors for comorbid CMBs in male AIS patients. CONCLUSION: There are gender differences in the influencing factors for CMBs in AIS patients. Age, old LIs, and blood glucose are independent risk or protective factors for comorbid CMBs in female AIS patients, although they are not associated with the risk of developing CMBs in male AIS patients.

Retinal Microvascular Diameters are Associated with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Objective: To investigate the association between retinal microvascular diameters and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 690 patients with T2DM were included in this retrospective study. Patients were divided into DKD and non-DKD groups according to urine microalbumin/creatinine ratio and estimated glomerular filtration rate. Retinal microvascular diameters were measured by the automated retinal image analysis system. Multivariate logistic regression analysis and restricted cubic splines were used to assess the relationships between the retinal microvascular diameters and DKD in patients with T2DM. Results: Multivariate logistic regression showed that widened diameters of retinal venules and narrowed diameters of retinal arterioles were associated with DKD after adjusting for potential confounding variables. There was a significant linear trend between the diameters of superior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.080), inferior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.111) and central retinal venular equivalent (CRVE) (P for trend < 0.001, P for non-linearity = 0.392) and risk of DKD in patients with T2DM. The restricted cubic splines showed that narrowed retinal arteriolar diameters, superior and inferior nasal retinal venulas were associated with the risk of DKD in a non-linear fashion (all P for non-linearity < 0.001). Conclusion: Wider retinal venular diameters and narrower retinal arteriolar diameters were associated with an increased risk of DKD in patients with T2DM. Widened retinal venular diameters, especially CRVE, superior and inferior temporal retinal venula, were positively associated with an increased risk of DKD in a linear fashion. In contrast, narrowed retinal arteriolar diameters were associated with the risk of DKD in a non-linear fashion.

Monitoring the Formation of Nickel-Poor and Nickel-Rich Oxide Cathode Materials for Lithium-Ion Batteries with Synchrotron Radiation.

The syntheses of Ni-poor (NCM111, LiNi1/3Co1/3Mn1/3O2) and Ni-rich (NCM811 LiNi0.8Co0.1Mn0.1O2) lithium transition-metal oxides (space group R3̅m) from hydroxide precursors (Ni1/3Co1/3Mn1/3(OH)2, Ni0.8Co0.1Mn0.1(OH)2) are investigated using in situ synchrotron powder diffraction and near-edge X-ray absorption fine structure spectroscopy. The development of the layered structure of these two cathode materials proceeds via two utterly different reaction mechanisms. While the synthesis of NCM811 involves a rock salt-type intermediate phase, NCM111 reveals a layered structure throughout the entire synthesis. Moreover, the necessity and the impact of a preannealing step and a high-temperature holding step are discussed.

Systemic Immune-Inflammation Index is Associated with Cerebral Small Vessel Disease Burden and Cognitive Impairment.

Objective: This study sought to explore the associations of the systemic immune-inflammation index (SII) with total cerebral small vessel disease (CSVD) burden and cognitive impairment. Methods: We enrolled 201 patients in the retrospective study with complete clinical and laboratory data. The SII was calculated as platelet count × neutrophil count/lymphocyte count. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Total CSVD burden was assessed based on magnetic resonance imaging. We performed logistic regression models, Spearman correlation, and mediation analysis to evaluate the associations of SII with CSVD burden and cognitive impairment. Results: After adjustment for confounding factors in the multivariate binary logistic regression model, elevated SII (odds ratio [OR], 3.263; 95% confidence interval [CI], 1.577-6.752; P = 0.001) or severe CSVD burden (OR, 2.794; 95% CI, 1.342-5.817; P = 0.006) was significantly associated with the risk of cognitive impairment. Correlation analyses revealed that SII levels were negatively associated with MMSE scores (rs = -0.391, P < 0.001), and positively associated with the total CSVD burden score (rs = 0.361, P < 0.001). Moreover, SII was significantly related to the severity of the CSVD burden (OR, 2.674; 95% CI, 1.359-5.263; P = 0.004). The multivariable-adjusted odds ratios (95% CI) in highest tertile versus lowest tertile of SII were 8.947 (3.315-24.145) for cognitive impairment and 4.945 (2.063-11.854) for severe CSVD burden, respectively. The effect of higher SII on cognitive impairment development was partly mediated by severe CSVD burden. Conclusion: Elevated SII is associated with severe CSVD burden and cognitive impairment. The mediating role of severe CSVD burden suggests that higher SII may contribute to cognitive impairment through aggravating CSVD burden.

Subclinical Hypothyroidism is Associated with Cognitive Impairment in Patients with Cerebral Small Vessel Disease.

Objective: To investigate the association between subclinical hypothyroidism (SCH) and cognitive function in patients with cerebral small vessel disease (CSVD). Methods: We evaluated 528 patients with CSVD in this retrospective study. SCH was defined as elevated levels of thyroid stimulating hormone with normal concentrations of free thyroxine. Magnetic resonance imaging was performed to assess the total CSVD burden score and the Montreal Cognitive Assessment was used to measure the cognitive function. Participants were grouped based on cognitive function or total CSVD burden score. Multivariate logistic regression and mediation analysis models were used to estimate the association of SCH with cognitive function and CSVD burden. Results: SCH was an independent risk factor for cognitive impairment in patients with CSVD after adjustment for potential confounding factors (OR: 1.939; 95% CI: 1.170 to 3.213; P=0.010). Additionally, SCH was independently associated with severe CSVD burden after adjustment for potential confounding factors (OR: 1.668; 95% CI: 1.085 to 2.564; P=0.020). Mediation analysis found a significant moderating effect (P=0.021) of the severe CSVD burden on the relation between SCH and cognitive impairment after adjustment for potential confounding factors. A 30.1% of the total effect between this relation was attributable to the presence of severe CSVD burden. Conclusion: SCH was associated with an increased risk of cognitive impairment in patients with CSVD. The mediating role of severe CSVD burden suggests that SCH may lead to cognitive impairment through the presence of severe CSVD burden. These findings may suggest strategies for screening for SCH in the context of cognitive impairment in patients with severe CSVD.

Baicalin facilitates remyelination and suppresses neuroinflammation in rats with chronic cerebral hypoperfusion by activating Wnt/ß-catenin and inhibiting NF-κB signaling.

One main factor contributing to the cognitive loss in vascular dementia (VD) is white matter lesions (WMLs) carried on by chronic cerebral hypoperfusion (CCH). A secondary neuroinflammatory response to CCH accelerates the loss and limits the regeneration of oligodendrocytes, leading to progressive demyelination and insufficient remyelination in the white matter. Thus, promoting remyelination and inhibiting neuroinflammation may be an ideal therapeutic strategy. Baicalin (BAI) is known to exhibit protective effects against various inflammatory and demyelinating diseases. However, whether BAI has neuroprotective effects against CCH has not been investigated. To determine whether BAI inhibits CCH-induced demyelination and neuroinflammation, we established a model of CCH in rats by occluding the two common carotid arteries bilaterally. Our results revealed that BAI could remarkably ameliorate cognitive impairment and mitigate CA1 pyramidal neuron damage and myelin loss. BAI exhibited enhancement of remyelination by increasing the expression of myelin basic protein (MBP) and oligodendrocyte transcription factor 2 (Olig2), inhibiting the loss of oligodendrocytes and promoting oligodendrocyte regeneration in the corpus callosum of CCH rats. Furthermore, BAI modified microglia polarization to the anti-inflammatory phenotype and inhibited the release of pro-inflammatory cytokines. Mechanistically, BAI treatment significantly induced phosphorylation of glycogen synthase kinase 3ß (GSK3ß), enhanced the expression of ß-catenin and its nuclear translocation. Simultaneously, BAI reduced the expression of nuclear NF-κB. Collectively, our results suggest that BAI ameliorates cognitive impairment in CCH-induced VD rats through its pro-remyelination and anti-inflammatory capacities, possibly by activating the Wnt/ß-catenin and suppressing the NF-κB signaling.

Dulaglutide Improves Gliosis and Suppresses Apoptosis/Autophagy Through the PI3K/Akt/mTOR Signaling Pathway in Vascular Dementia Rats.

Dulaglutide is a new type of hypoglycemic agent that agonizes glucagon-like peptide-1 receptor (GLP-1RA). It can be concluded from previous studies that a GLP-1RA can reduce apoptosis and regulate autophagy in the nervous system, while related research on dulaglutide in vascular dementia (VD) has not been reported. In our study, the VD rat model was established by bilateral carotid artery occlusion, and the results of the Morris water maze test (MWM) and open-field test showed that the application of dulaglutide could effectively reduce the cognitive decline of VD rats without changing the behavior in the open-field test, which was used to assess an anxiety-like phenotype. We applied HE staining and immunofluorescence labeling to show that dulaglutide treatment significantly alleviated neuronal damage in the hippocampal region of VD rats, and reduced microglial and astrocyte proliferation. Western blot results showed that dulaglutide reduced VD-induced neuronal apoptosis (BCL2/BAX, c-caspase3) and autophagy (P62, LC3B, Beclin-1), and upregulated phosphorylation of PI3K/Akt/mTOR signaling pathway. KEGG pathway analysis of RNA-Sequence results showed that the differentially expressed genes in the dulaglutide treatment group were significantly enriched in the mTOR signaling pathway, and the repressor of mTOR, Deptor, was down-regulated. In conclusion, this study suggested that dulaglutide may alleviate learning and memory impairment and neuron damage in VD rats by attenuating apoptosis, regulating autophagy, and activating the PI3K/Akt/mTOR signaling pathway in neurons, which may make it a promising candidate for the simultaneous treatment of VD and diabetes.

Retinal thickness changes in different subfields reflect the volume change of cerebral white matter hyperintensity.

Purpose: To investigate the relationship between the retinal thickness in different subfields and the volume of white matter hyperintensity (WMH), with the hope to provide new evidence for the potential association between the retina and the brain. Methods: A total of 185 participants aged over 40 years were included in our study. Magnetic resonance imaging (MRI) was used to image the WMH, and WMH volume was quantitatively measured by a specific toolbox. The thickness of the total retina, the retinal nerve fiber layer (RNFL), and the ganglion cell and inner plexiform layer (GCIP) was measured by optical coherence tomography (OCT) in nine subfields. The association between retinal thickness and WMH volume was demonstrated using binary logistic regression and Pearson correlation analysis. Results: Participants were divided into two groups by the WMH volume (‰, standardized WMH volume) median. In the quartile-stratified binary logistic regression analysis, we found that the risk of higher WMH volume showed a positive linear trend correlation with the thickness of total retina (95% CI: 0.848 to 7.034; P for trend = 0.044)/ GCIP (95% CI: 1.263 to 10.549; P for trend = 0.038) at the central fovea, and a negative linear trend correlation with the thickness of nasal inner RNFL (95% CI: 0.086 to 0.787; P for trend = 0.012), nasal outer RNFL (95% CI: 0.058 to 0.561; P for trend = 0.004), and inferior outer RNFL (95% CI: 0.081 to 0.667; P for trend = 0.004), after adjusting for possible confounders. Correlation analysis results showed that WMH volume had a significant negative correlation with superior outer RNFL thickness (r = -0.171, P = 0.02) and nasal outer RNFL thickness (r = -0.208, P = 0.004). Conclusion: It is suggested that central fovea and outer retina thickness are respectively associated with WMH volume. OCT may be a biological marker for early detection and longitudinal monitoring of WMH.

Cerebral small vessel disease mediates the association between homocysteine and cognitive function.

Objective: To investigate the relations of serum total homocysteine (tHcy) with cerebral small vessel disease (CSVD) and cognitive function and evaluate whether CSVD mediates the effect of serum tHcy on cognitive function. Methods: A total of 1,033 consecutive eligible participants who received serum tHcy, brain magnetic resonance imaging (MRI), and neuropsychological assessment were included in this retrospective study. White matter hyperintensity, lacune, cerebral microbleed, and enlarged perivascular space were evaluated based on brain MRI. We used multivariate binary logistic regression analysis, multivariate ordinal logistic regression analysis, and mediation analyses to assess the relations of serum tHcy with CSVD and cognitive function. Results: Serum tHcy levels were higher in patients with cognitive impairment than those with no cognitive impairment. Logistic regression analyses showed elevated serum tHcy was associated with cognitive impairment [odds ratio (OR): 10.475; 95% confidence interval (CI): 4.522 to 24.264; p < 0.001] and a higher CSVD burden score (OR: 17.151; 95% CI: 8.785 to 33.921; p < 0.001) after adjusting potential confounders. Compared with the lowest tHcy quartile, the multivariable-adjusted OR of the highest quartile was 4.851 (95% CI: 3.152 to 7.466; p for the trend < 0.001) for cognitive impairment, 3.862 (95% CI: 2.467 to 6.047; p for the trend < 0.001) for a severe CSVD burden score. Mediation analyses showed significant moderating effects (9.3-23.6%) by different imaging markers of CSVD on the association between higher serum tHcy levels and cognitive impairment. Conclusion: Elevated serum tHcy is associated with cognitive impairment and the development of CSVD. A proportion of the association between elevated serum tHcy and cognitive impairment may be attributed to the presence of different imaging markers of CSVD, especially the severe CSVD burden score.

Triglyceride glucose index is associated with cerebral small vessel disease burden and cognitive impairment in elderly patients with type 2 diabetes mellitus.

Objective: To investigate the relations of Triglyceride glucose (TyG) index with cerebral small vessel disease (CSVD) burden and cognitive function in aged patients with type 2 diabetes mellitus (T2DM). Methods: A total of 308 elderly patients with T2DM were included in this retrospective study. The standardized Chinese version of Mini-Mental State Examination was used to assess cognitive function. The total CSVD burden score was assessed by combining four imaging markers of CSVD, including the presence of white matter hyperintensity, cerebral microbleeds in the deep, lacunes and enlarged perivascular spaces in the basal ganglia. The TyG index was calculated as the formula of ln [fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. We used logistic regression analysis and mediation analysis to investigate the relations of TyG index with CSVD and cognitive function. Results: Multivariate binary logistic regression analysis showed that increased TyG index (OR: 2.241; 95% Confidence Interval(CI): 1.439 to 3.490; P <0.001), or severe CSVD burden (OR: 2.198; 95% CI: 1.283 to 3.763; P = 0.004) was associated with an increased risk of cognitive impairment in elderly patients with T2DM after adjusting for potential confounders. In addition, TyG index was an independent risk factor of severe CSVD burden (OR: 1.472; 95% CI: 1.003 to 2.160; P = 0.048) after controlling for potential confounders. Compared with the lowest TyG index tertile, the multivariable-adjusted OR of the highest tertile was 3.298 (95% CI: 1.685 to 6.452; P for trend <0.001) for cognitive impairment, 1.933 (95% CI: 1.010 to 3.698; P for trend = 0.047) for severe CSVD burden. Mediation analysis found a significant moderating effect of the severe CSVD burden on the association between higher TyG index levels and cognitive impairment. Conclusions: The increased TyG index is an independent risk factor for cognitive impairment and severe CSVD burden in clinical practice. A proportion of the effect of increased TyG index on cognitive impairment may be due to the aggravation of CSVD burden.

Cerebral Small Vessel Disease is Associated with Mild Cognitive Impairment in Type 2 Diabetes Mellitus.

Objective: Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment, but the underlying cerebral small vessel disease (CSVD)-related structural brain correlates are unclear. The aim of this study was to investigate the relationship between various imaging markers of CSVD and mild cognitive impairment (MCI) in patients with T2DM. Methods: A total of 228 eligible participants with T2DM who were divided into MCI group and normal cognitive group based on neuropsychological assessment were enrolled in this retrospective study. White matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVS) were evaluated based on brain magnetic resonance imaging (MRI). The total CSVD burden score was calculated by combining the above four markers of CSVD. Binary logistic regression analysis was used to evaluate the relationship between different imaging markers of CSVD and MCI in patients with T2DM. Kruskal-Wallis test and Jonckheere-Terpstra test were used to compare mean MoCA scores among individuals with varying CSVD markers. Results: In the multivariate binary logistic regression analyses, moderate or severe total CSVD burden (OR: 3.29, 95% CI: 1.63-7.38, P=0.004; OR: 10.97, 95% CI: 4.94-24.34, P<0.001, respectively), moderate dWMH (OR: 3.26, 95% CI: 1.43-7.41, P=0.005), extensive lacunes (OR: 4.97, 95% CI: 1.79-13.81, P=0.002), and moderate BG-EPVS (OR: 3.84, 95% CI: 1.81-8.13, P<0.001) were associated with MCI in patients with T2DM related to MCI after adjusting for potential confounders. There was a trend for significant decrease in MoCA scores with increase severity of dWMH, pWMH, lacunes, BG-EPVS, deep CMBs, or total CSVD burden (P for trend <0.05). Conclusion: Different imaging markers of CSVD, particularly total CSVD burden, were associated with an increased risk of MCI and decline in MoCA scores in patients with T2DM. These findings may provide clues for future studies to explore early diagnostic imaging markers of cognitive impairment in relation to T2DM.

Long-Term Use of Metformin Is Associated With Reduced Risk of Cognitive Impairment With Alleviation of Cerebral Small Vessel Disease Burden in Patients With Type 2 Diabetes.

Objective: Type 2 diabetes (T2D) is a risk factor for cognitive impairment and cerebral small vessel disease (CSVD). The relation of metformin use and cognitive impairment or CSVD is not clear. The objective of this study was to investigate the cross-sectional effects of long-term use of metformin on total CSVD burden and cognitive function in patients with T2D. Methods: A total of 234 participants with T2D from the memory clinic in Hebei General Hospital were enrolled in this retrospective study. Duration of metformin use and dosage were recorded. Along with cerebral magnetic resonance imaging (MRI) examination, Mini-Mental State Examination (MMSE) was also performed to assess their cognitive status. We determined the validated total CSVD score (ranging from 0-4) by combining four markers of CSVD that were visually rated. We used binary logistic regression analysis, ordinal logistic regression analysis and mediation analysis to assess the relation of long-term use of metformin with CSVD burden and cognitive function. Results: Binary logistic regression analysis showed long-term use of metformin was associated with reducing the risk of cognitive impairment (OR: 0.446; 95% Confidence Interval (CI): 0.249 to 0.800; P = 0.007), after adjustment of potential confounders, such as total CSVD burden score, age, HbA1c, hypertension, history of stroke, homocysteine, body mass index, TG and HDL-C. Ordinal logistic regression analysis suggested that long-term use of metformin was associated with alleviation of total CSVD burden score (OR: 0.583; 95% CI: 0.359 to 0.943; P = 0.027), after adjusting for age, HbA1c, hypertension, history of stroke, homocysteine, body mass index, TG and HDL-C. Mediation analysis showed significant mediation by the presence of severe CSVD burden score for long-term use of metformin in relation to cognitive impairment. Conclusion: Long-term use of metformin was associated with lower rates of cognitive impairment and lower total CSVD burden score in patients with T2D. A proportion of the relation between long-term use of metformin and cognitive impairment may be attributable to alleviation of CSVD burden.

Homocysteine is Associated with the Development of Cerebral Small Vessel Disease: Retrospective Analyses from Neuroimaging and Cognitive Outcomes.

OBJECTIVE: As the population ages, a growing burden of cerebral small vessel disease (cSVD) has sparked extensive concerns recently. Homocysteine (Hcy), as a traditional risk factor for atherosclerosis, may also participate in the development of cSVD. By comprehensively assessing Hcy's correlation with different MRI markers of cSVD and cognitive outcomes in a homogeneous population with cSVD, this study aims to explore the value of Hcy in the clinical management of cSVD. METHODS: 231 inpatients with MRI-confirmed cSVD were enrolled in this retrospective study (mean age 66.4±10.0 years, male sex 47.6%). Along with brain MRI and plasma total Hcy (tHcy) examination, Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were also performed to assess their global cognitive function. Burdens of cSVD neuroimaging features encompassing white matter hyperintensity (WMH), lacunes of presumed vascular origin, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS) were evaluated based on brain MRI demonstrations. RESULTS: After adjusting for possible confounders, statistical analyses showed that plasma tHcy levels were not only correlated with burdens of deep/periventricular WMH (P < 0.001, P for trend < 0.001; P < 0.001, P for trend < 0.001), lacunes (P < 0.001, P for trend < 0.001), lobar CMBs (P = 0.002), and EPVS in the basal ganglia (P < 0.001, P for trend = 0.002) but also remained an independent predictor of cognitive impairment (B=-0.159, 95%CI -0.269--0.049, P = 0.005, P for trend < 0.001) in the patients with cSVD. CONCLUSIONS: Plasma tHcy levels are associated with the development of cSVD in a dose-independent manner and may predict the cognitive outcomes in cSVD patients. These findings provide a potential clue to cSVD's physiopathology and future disease management.

Data on prevalence of atrial fibrillation and its association with stroke in low-, middle-, and high-income regions of China.

Data presented in this article are supplementary material to our research article entitled " Prevalence of Atrial Fibrillation in Different Socioeconomic Regions of China and Its Association with Stroke: Results from a National Stroke Screening Survey" (Wang et al., 2018) [1]. This data article summarizes previous studies of Atrial Fibrillation (AF) prevalence in China, and estimates the association between AF and stroke in different socioeconomic regions of China through a national survey.

Prevalence of atrial fibrillation in different socioeconomic regions of China and its association with stroke: Results from a national stroke screening survey.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. This study aimed to estimate the prevalence of AF in different socioeconomic regions of China and identify its association with stroke, through a national survey. METHODS: The study included 726,451 adults aged ≥40 years who were participants of the China National Stroke Screening and Prevention Project, a nationally representative cross-sectional study. Stepwise logistic regression analyses were conducted to investigate the association between AF and stroke. RESULTS: The overall standardized prevalence rate of AF was 2.31%. The prevalence of AF was highest in high-income regions (2.54%), followed by middle-income regions (2.33%), and lowest in low-income regions (1.98%). Women had a higher prevalence of AF than men in all regions (low-income regions, 2.30% vs 1.65%; middle-income regions, 2.78% vs 1.89%; and high-income regions, 2.96% vs 2.12%). Compared with urban residents, the prevalence of AF among rural residents was higher in low- (2.03% vs 1.91%) and middle-income regions (2.69% vs 1.90%), but lower in high-income regions (2.44% vs 2.58%). Participants with AF were more likely to have a stroke than those without AF (9.48% vs 2.26%). After adjusting for age, sex, location, overweight or obese, smoking, drinking, physical inactivity, hypertension, diabetes, dyslipidemia, and a family history of stroke, results showed that AF was significantly associated with stroke. CONCLUSIONS: The prevalence of AF has increased in recent years, and it was positively correlated with socioeconomic status, sex (women), location (rural areas), and stroke.

Edaravone attenuates oxidative stress induced by chronic cerebral hypoperfusion injury: role of ERK/Nrf2/HO-1 signaling pathway.

Objectives The potential protective effects and mechanisms of edaravone have not been well elucidated in vascular dementia (VaD) induced by chronic cerebral hypoperfusion (CCH). The aim of this study was to investigate whether edaravone could improve cognitive damage in rats induced by CCH, and whether the effects of edaravone were associated with ERK/Nrf2/HO-1 signaling pathway. Methods CCH was induced by bilateral common carotid arteries occlusion (BCCAO). Sprague-Dawley (SD) rats were randomly divided into four groups: sham (sham-operated) group, vehicle (BCCAO + normal saline) group, edaravone3.0 group and edaravone6.0 group. The edaravone3.0 and edaravone6.0 group rats were provided 3.0 mg/kg and 6.0 mg/kg of edaravone, respectively, intraperitoneal (i.p.) injection twice daily following the first day after BCCAO. In this experiment, the spatial learning and memory were assessed using the Morris water maze. The malondialdehyde (MDA) contents and superoxide dismutase (SOD) activities in the hippocampus were measured biochemically. And, the levels of total ERK1/2 (t-ERK1/2), Phospho-ERK1/2 (p-ERK1/2), total Nrf2 (t-Nrf2), nuclear Nrf2 (n-Nrf2), and HO-1 were assessed by western blot. Results The results showed that the treatment with edaravone significantly improved CCH-induced cognitive damage, and boosted endogenous antioxidants SOD activity and HO-1 level, decreased MDA contents in the hippocampus by activating Nrf2 signaling pathway which was related to ERK1/2. We also found that the neuronal morphology of the hippocampal CA1 area significantly improved and the number of Nrf2 positive cells markedly increased in the edaravone treatment groups. Conclusion Our results demonstrated a neuroprotective effect of edaravone on hippocampus against oxidative stress and cognitive deficit induced by CCH. The mechanism may be related to the enhancement of antioxidant defense system by activating ERK/Nrf2/HO-1 signaling pathway.

Cerebral small vessel disease and post-stroke cognitive impairment.

Cerebral small vessel disease (CSVD) refers to a group of pathological processes with multifarious etiologies that affect the small arteries, arterioles, venules, and capillaries of the brain. Features seen on neuroimaging include white matter hyperintensities, lacunar infarction, cerebral microbleeds, brain atrophy, microinfarcts and enlarged perivascular spaces (EPVS). CSVD gives rise to one in five strokes worldwide and is a leading cause of cognitive impairment and dementia, especially in the elderly. Post-stroke cognitive impairment (PSCI) is one of the most common subtypes of cognitive impairment. The underlying mechanisms of PSCI are not known in detail. A growing body of evidence has been suggesting that CSVD plays an important role in the pathogenesis of PSCI. This article reviews the advances in research on the relationship between CSVD and PSCI.