Vascular Cognitive Impairment Group Research Articles

Evaluation of glymphatic system activity by diffusion tensor image analysis along the perivascular space (DTI-ALPS) in dementia patients.

Dementia is a clinical syndrome caused by multiple etiologies, usually manifests with progressive and diffuse brain dysfunction. The activity of the human glymphatic system was evaluated in cases of dementia by the diffusion tensor image analysis along the perivascular space (DTI-ALPS). We recruited 28 healthy subjects and 77 patients, including 38 with Alzheimer's disease (AD),18 with mild cognitive impairment (MCI), 28 with normal controls (NC) and 21 with vascular cognitive impairment (VCI). All participants underwent DTI scanning. Diffusivities in the X, Y and Z axes were obtained in the lateral ventricle body plane of all subjects. We assessed the diffusivity along the perivascular spaces, as well as projection fibers and association fibers, respectively, in order to acquire an DTI-ALPS-index and correlated them with mini mental state examination (MMSE) and montreal cognitive assessment (MOCA) scores using partial correlation which the influence of age was controlled. The AD, MCI, and VCI patients showed significantly lower DTI-ALPS-index (p < 0.001) compared to the NC. Besides, the VCI group had significantly higher DTI-ALPS-index than the AD group (p = 0.007). There was a significant positive correlation between DTI-ALPS-index and MMSE and MOCA scores (the effect of age was controlled), showing that lower water diffusivity along the perivascular spaces associated with dementia.The higher Dzassoc led to the reduced DTI-ALPS-index in VCI, while lower Dxassoc contributed to the decrease of DTI-ALPS-index in AD. The evaluation of DTI-ALPS demonstrates impairment of the glymphatic system in dementia patients by decreased DTI-ALPS-index. Different from AD, the VCI patients show glymphatic drainage disorder rather than glymphatic system impairment. This article comprehensively covers several types of dementia and performs the comparison of VCI, AD and MCI in glymphatic system dysfunction.

Structural and functional activities of brain in patients with vascular cognitive impairment: A case-controlled magnetic resonance imaging study.

This study aimed to identify abnormal brain regions and imaging indices of vascular cognitive impairment (VCI) and explore specific imaging diagnostic markers of VCI. In this study, 24 patients with VCI were allocated to the VCI group and 25 healthy subjects were assigned to the healthy control (HC) group. Demographic data and neuropsychological test scores were compared using SPSS 25.0. The structural and functional imaging data were post-processed and statistically analyzed using CAT12, DPARSF and SPM12 software, based on the MATLAB platform. The structural and functional indices of gray matter volume (GMV) and regional homogeneity (ReHo) were obtained, and inter-group data were analyzed using an independent-sample t test. Sex, age, years of education, and total brain volume were used as covariates. Compared to the HC group, the GMV of VCI in the VCI group decreased significantly in the rectus muscles of the bilateral gyrus, left superior temporal gyrus, left supplementary motor area (SMA), right insula, right superior temporal gyrus, right anterior cuneiform lobe, and right anterior central gyrus (PRECG) (P < .05, FWE correction), without GMV enlargement in the brain area. ReHo decreased in the right inferior temporal gyrus (ITG), right parahippocampal gyrus, and left temporal pole (middle temporal gyrus, right lingual gyrus, left posterior central gyrus, and right middle temporal gyrus), the areas of increased ReHo were the left caudate nucleus, left rectus gyrus, right anterior cingulate gyrus and lateral cingulate gyrus (P < .05, FWE correction). Correlation analysis showed that the GMV of the left superior temporal gyrus was positively correlated with the Montreal Cognitive Assessment (MoCA) score (P < .05), and the GMV of the right insula was positively correlated with the MESE and long delayed memory scores (P < .05). There was a significant positive correlation between the ReHo and short-term delayed memory scores in the middle temporal gyrus of the left temporal pole (P < .05). The volume of GMV and ReHo decreased in VCI patients, suggesting that impairment of brain structure and function in specific regions is the central mechanism of cognitive impairment in these patients. Meanwhile, the functional indices of some brain regions were increased, which may be a compensatory mechanism for the cognitive impairment associated with VCI.

18F-FDG PET and a classifier algorithm reveal a characteristic glucose metabolic pattern in adult patients with moyamoya disease and vascular cognitive impairment.

Vascular cognitive impairment (VCI) is a critical issue in moyamoya disease (MMD). However, the glucose metabolic pattern in these patients is still unknown. This study aimed to identify the metabolic signature of cognitive impairment in patients with MMD using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) and establish a classifier to identify VCI in patients with MMD. One hundred fifty-two patients with MMD who underwent brain 18F-FDG PET scans before surgery were enrolled and classified into nonvascular cognitive impairment (non-VCI, n = 52) and vascular cognitive impairment (VCI, n = 100) groups according to neuropsychological test results. Additionally, thirty-three health controls (HCs) were also enrolled. Compared to HCs, patients in the VCI group exhibited extensive hypometabolism in the bilateral frontal and cingulate regions and hypermetabolism in the bilateral cerebellum, while patients in the non-VCI group showed hypermetabolism only in the cerebellum and slight hypometabolism in the frontal and temporal regions. In addition, we found that the patients in the VCI group showed hypometabolism mainly in the left basal ganglia compared to those in the non-VCI group. The sparse representation-based classifier algorithm taking the SUVr of 116 Anatomical Automatic Labeling (AAL) areas as features distinguished patients in the VCI and non-VCI groups with an accuracy of 82.4%. This study demonstrated a characteristic metabolic pattern that can distinguish patients with MMD without VCI from those with VCI, namely, hypometabolic lesions in the left hemisphere played a more important role in cognitive decline in patients with MMD.

Correlations among peripheral blood markers, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events.

Both inflammation and cerebral white matter injury are closely associated with vascular cognitive impairment (VCI). The aim of this study was to analyze the correlation between peripheral serological markers, white matter injury, and cognitive function in patients with non-disabling ischemic cerebrovascular events (NICE); to identify potential biological markers for the diagnosis and prediction of VCI; and to provide a basis for the early diagnosis and intervention of VCI. We collected clinical data, along with demographic and medical history data, from 151 NICE patients. Fasting venous blood samples were collected. Based on the Montreal Cognitive Assessment (MoCA) after admission, we divided the patients into normal cognitive function (NCF) and VCI groups, and then classified them into mild white matter hyperintensity (mWMH) and severe white matter hyperintensity (sWMH) based on Fazekas scores. The differences in serological marker levels were compared between the cognitive function groups and the white matter hyperintensity groups. Binary logistic regression models and receiver operating characteristic curves were used to analyze the diagnostic predictive value of serological markers for VCI in patients with NICE and in the white matter hyperintensity subgroups. Among 151 patients with NICE, 95 were male and 56 were female. Lymphocyte count (OR = 0.405, p = 0.010, 95% CI [0.201, 0.806]), red blood cell count (OR = 0.433, p = 0.010, 95% CI [0.228, 0.821]), and hemoglobin level (OR = 0.979, p = 0.046, 95% CI [0.958, 0.999]) were protective factors for cognitive function in patients with NICE. The sWMH group had a higher age, granulocyte/lymphoid ratio (NLR), and neutrophil percentage but a lower MoCA score, hemoglobin level, and lymphocyte count than the mWMH group. In the mWMH group, lymphocyte count (AUC = 0.713, p = 0.003, 95% CI [0.593, 0.833]) had an acceptable predictive value for the diagnosis of VCI, whereas white blood cell count (AUC = 0.672, p = 0.011, 95% CI [0.545, 0.799]), red blood cell count (AUC = 0.665, p = 0.014, 95% CI [0.545, 0.784]), and hemoglobin level (AUC = 0.634, p = 0.047, 95% CI [0.502, 0.765]) had marginal predictive value for the diagnosis of VCI. In the sWMH group, no significant differences were found in serological markers between the NCF and VCI groups. Lymphocyte count, red blood cell count, and hemoglobin level were independent protective factors for cognitive function in patients with NICE; they can be used as potential biological markers to distinguish VCI in patients with NICE and are applicable to subgroups of patients with mWMH.

[Effects of total saponins from Trillium tschonoskii Maxim on vascular cognitive impairment and its mechanisms].

Objective: To investigate neuroprotective effects of total saponins from Trillium tschonoskii Maxim (TST) on vascular cognitive impairment (VCI) rats through inflammatory body of the NOD-like body protein 3 (NLRP3) regulated by endoplasmic reticulum stress (ERS). Methods: SD rats were divided into sham-operated group (SHAM), model group (VCI, bilateral neck arterial ligation (BCCAO) method), TST intervention group (TST, 100 mg/kg), and positive group (donepezil hydrochloride, 0.45 mg/kg ), continuous administration for 4 weeks. The ability of learning and memory was evaluated by the morris water labor. The tissue pathological changes were observed by HE and NISSL staining. Western blot was used to detectendoplasmic reticulum-related proteins GRP78, IRE1, XBP1. Inflammasome-related proteins NLRP3, ASC, Caspase-1, IL-18, IL-1β. Results: Compared with the SHAM group, the escape latency of VCI group rats was prolonged significantly, and the number of times of crossing the platform and the percentage of target quadrant residence time were shortened (P＜0.01); The cells in the hippocampus of VCI rats were damaged, with obvious pyknosis, decreased number of neurons and damage of cell body structure; The endoplasmic reticulum and inflammatory corpuscle-associated proteins were increased in VCI group (P＜0.05 or P＜0.01). Compared with the VCI group, the TST group and the positive group had less time to search for the platform, and the ratio of the times of crossing the platform to the time in the target quadrant was longer (P＜0.05 or P＜0.01). There was no significant difference in the times of crossing the platform between the positive group and VCI group (P＞0.05); The cell damage, nuclear pyknosis and the number of neurons in TST and positive groups were significantly reduced; The endoplasmic reticulum associated proteins and inflammatory body associated proteins in TST group and positive group were decreased to different degrees (P＜0.05 or P＜0.01). Conclusion: TST has neuroprotective effects on VCI rats, and its mechanism may be related to the involvement of ERS in the regulation of NLRP3 inflammatory small bodies.

Effect and Mechanism of Yisui Fuyongtang (YSFYT) Decoction on Cognitive Function and Synaptic Plasticity in Rats with Vascular Cognitive Impairment.

Vascular cognitive impairment (VCI) has emerged as the second major disease responsible for dementia, and there is still a lack of effective treatment methods for this disorder to date. Clinical medications have found that Yisui Fuyongtang (YSFYT) Decoction is effective in improving neurological signs and learning-memory functions in patients who develop white matter lesions and whole brain atrophy. To clarify the effect and molecular regulation mechanism of YSFYT Decoction on model rats, this research analyzed the influence of YSFYT Decoction on the learning-memory ability and lipid metabolism of rats based on behavioral and biochemical analysis. Further pathology and protein detection methods were adopted to investigate the action of YSFYT Decoction on the neurons in the hippocampus of model rats and the regulation of the brain derived neurotrophic factor (BDNF)-tyrosine protein kinase receptor B (TrkB) signaling pathway. Compared with the VCI group, after YSFYT Decoction administration, the ratio of swimming time in the platform, number of crossing the platform, number of active avoidance, and proportion of active avoidance of the rats were markedly increased, whereas the response latency was substantially reduced (p < 0.05). Biochemical tests indicated that contents of lipoprotein lipase (LPL), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) of the model rats in YSFYT Decoction treatment group were greatly reduced, whereas those of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD) were elevated (p < 0.05). Additionally, Bcl-2 expression in YSFYT Decoction treatment group was significantly increased, but neuron apoptosis of the hippocampus tissue was reduced. Meanwhile, neuron number was apparently higher than that in VCI model group. Following Yisui Decoction treatment, expressions of growth-associated protein 43 (GAP43), synaptophysin (SYP), postsynaptic density 95 (PSD95), NMDAR subunit 2B (NR2B), BDNF, TrkB, phospho-mitogen-activated protein kinase (p-MAPK), extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), and phospho-protein kinase B (p-AKT) were markedly elevated. Taken together, YSFYT Decoction could activate the BDNF-TrkB signaling pathway, elevate Bcl-2 expression, and minimize neuronal apoptosis in hippocampus, thereby improving the behavioral characteristics and biochemical indicators of the VCI rat model.

Erythrocytes Are an Independent Protective Factor for Vascular Cognitive Impairment in Patients With Severe White Matter Hyperintensities.

Background and Purpose: Hemoglobin is one of the main proteins in erythrocytes. There are significant correlations between low hemoglobin and white matter hyperintensities (WMH) and cognitive impairment. This study explored whether erythrocytopenia has predictive value for vascular cognitive impairment (VCI) in patients with WMH.Method: We conducted a cross-sectional study of 302 patients, including 62 with cerebral small vessel disease and 240 with stroke. Basic demographic data and fasting blood were collected. First, all patients were divided into normal cognition (NC), mild VCI (mVCI), and severe VCI (sVCI) groups (subgroups later) based on cognitive behavior scores. Second, all patients were divided into mild WMH (mWMH) and severe WMH (sWMH) groups based on Fazekas scores. The differences in blood markers between different groups or subgroups with different cognitive levels were analyzed by univariate analysis. Then, binary logistic regression was used to analyze the diagnostic value of erythrocyte counts for VCI in the sWMH group, and ordinal logistic regression was used to analyze the predictive value of multiple variables for different cognitive levels.Results: Univariate analysis showed that erythrocytes, hemoglobin, high-sensitivity C-reactive protein, retinol binding protein and prealbumin were potential blood markers for different cognitive levels in sWMH patients. Among them, erythrocytopenia has good predictive value for the diagnosis of mVCI (AUC = 0.685, P = 0.008) or sVCI (AUC = 0.699, P = 0.003) in patients with sWMH. Multivariate joint analysis showed that erythrocytes were an independent protective factor reducing the occurrence of VCI in patients with sWMH (OR = 0.633, P = 0.045). Even after adjusting for age, there was still a significant difference (P = 0.047).Conclusion: Erythrocytes are an independent protective factor for VCI in patients with sWMH. Promoting hematopoietic function may have potential value for prevention of cognitive decline in patients with cerebrovascular disease.

Impact of Brain MRI Markers on Major and Mild Vascular Cognitive Impairment in CADASIL

Background: Cognitive impairment is the second most common clinical manifestation in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, understanding of cognitive impairment in CADASIL has been hampered by lack of consensus on diagnosis of vascular cognitive impairment (VCI). We used vascular impairment of cognition classification consensus study principles (VICCCS-1) and protocols (VICCCS-2) to assess the cognitive impairment in CADASIL. We also evaluated the impact of MRI markers on major and mild VCI in CADASIL.Methods: We prospectively recruited 64 patients who underwent standardized brain MRI and detailed neuropsychological test. MRI analysis included number of lacunes, number of cerebral microbleeds (CMB), normalized volume of white-matter hyperintensities (nWMH), and brain parenchymal fraction (BPF). BPF has been used to measure brain atrophy. The patients were divided into three groups: those with normal cognition (CADASIL-NC, n=14), those with mild VCI (CADASIL-mild VCI, n=38), and those with major VCI (CADASIL-major VCI, n=11).Results: The three groups differed according to age, with the major VCI group being older. The major VCI group had more lacunes, more CMB, more extensive white matter lesions and lower BPF than NC group. There were no significant differences between NC and mild VCI groups in BPF. BPF and age were the independent predictors of major VCI. There was a tendency that women were at higher risk for mild VCI, though it did not reach statistical significance. Women were older than men, but had lower number of lacunes in mild VCI.Conclusions: These findings suggest that brain atrophy and age are the main predictors of major VCI in CADASIL.

Predictive value of serum adiponectin and hemoglobin levels for vascular cognitive impairment in ischemic stroke patients.

Objectives:To investigate the potential predictive value of serum adiponectin (APN) and hemoglobin (Hb) levels for the occurrence of vascular cognitive impairment in ischemic stroke patients.Methods:Eighty ischemic stroke patients, admitted to our hospital between June 2019 and November 2020, were retrospectively divided into no cognitive impairment (NCI) group (n=43) and cognitive impairment (CI) group (n=37) based on Montreal Cognitive Assessment (MoCA) scale scoring at three months follow-up. ELISA was used to assess serum Hb and APN levels and receiver operating characteristic (ROC) curves were created to evaluate correlation.Results:Serum APN and Hb levels were lower in the vascular cognitive impairment group compared to non-impaired counterparts. Pearson correlation analysis showed that both APN and Hb levels were positively correlated with MoCA scores. Area under curve analysis indicated predictive value for serum APN and Hb for predicting cognitive impairment in ischemic stroke patients.Conclusion:Serum APN and Hb levels in ischemic stroke patients have value for predicting vascular cognitive impairment and may be suitable for helping dictate treatment planning.

Magnetic Resonance Image Feature Analysis under Deep Learning in Diagnosis of Neurological Rehabilitation in Patients with Cerebrovascular Diseases.

To explore the impact of magnetic resonance imaging (MRI) image features based on deep learning algorithms on the neurological rehabilitation of patients with cerebrovascular diseases, eighty patients with acute cerebrovascular disease were selected as the research objects. According to whether the patients were with vascular cognitive impairment (VCI), they were divided into VCI group (34 cases) and non-VCI group (46 cases). In addition, based on the convolutional neural network (CNN), a new multimodal CNN image segmentation algorithm was proposed. The algorithm was applied to the segmentation of MRI images of patients with vascular cognitive impairment (VCI) and compared with the segmentation results of CNN and fully CNN (FCN). As a result, the segmentation results of the three different algorithms showed that the Dice coefficient, accuracy, and recall of the multimodal CNN algorithm were 0.78 ± 0.24, 0.81 ± 0.28, and 0.88 ± 0.32, respectively, which were significantly increased compared to those of other two algorithms (P < 0.05). The neurological evaluation results showed that the MMSE and MoCA scores of VCI patients were 15.4 and 14.6 ± 5.31, respectively, which were significantly lower than those of the non-VCI group (P < 0.05). The TMT-a and TMT-b scores of VCI patients were 221.7 and 385.9, respectively, which were significantly higher than those of the non-VCI group (P < 0.05). The FA and MD values of nerve function-related fibers shown in the MRI images of the VCI group were significantly different from those of the non-VCI group (P < 0.05). Therefore, the neurological recovery process of VCI patients was affected by multiple neurocognitive-related fiber structures. To sum up, the multimodal CNN algorithm can sensitively and accurately reflect the degree of neurological impairment in patients with cerebrovascular disease and can be applied to disease diagnosis and neurological evaluation of VCI patients.

Plasma osteopontin as a biomarker of Alzheimer\u2019s disease and vascular cognitive impairment

Cerebrovascular disease (CeVD) and neurodegenerative dementia such as Alzheimer’s disease (AD) are frequently associated comorbidities in the elderly, sharing common risk factors and pathophysiological mechanisms including neuroinflammation. Osteopontin (OPN) is an inflammatory marker found upregulated in vascular diseases as well as in AD. However, its involvement in vascular dementia (VaD) and pre-dementia stages, namely cognitive impairment no dementia (CIND), both of which fall under the spectrum of vascular cognitive impairment (VCI), has yet to be examined. Its correlations with inflammatory cytokines in cognitive impairment also await investigation. 80 subjects with no cognitive impairment (NCI), 160 with CIND and 144 with dementia were included in a cross-sectional study on a Singapore-based memory clinic cohort. All subjects underwent comprehensive clinical, neuropsychological and brain neuroimaging assessments, together with clinical diagnoses based on established criteria. Blood samples were collected and OPN as well as inflammatory cytokines interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF) were measured using immunoassays. Multivariate regression analyses showed significant associations between increased OPN and VCI groups, namely CIND with CeVD, AD with CeVD and VaD. Interestingly, higher OPN was also significantly associated with AD even in the absence of CeVD. We further showed that increased OPN significantly associated with neuroimaging markers of CeVD and neurodegeneration, including cortical infarcts, lacunes, white matter hyperintensities and brain atrophy. OPN also correlated with elevated levels of IL-6, IL-8 and TNF. Our findings suggest that OPN may play a role in both VCI and neurodegenerative dementias. Further longitudinal analyses are needed to assess the prognostic utility of OPN in disease prediction and monitoring.

Addition of Aβ42 to Total Cerebral Small Vessel Disease Score Improves the Prediction for Cognitive Impairment in Cerebral Small Vessel Disease Patients.

PurposeTo investigate the associations between concentrations of Aβ40 and Aβ42 and vascular cognitive impairment (VCI) in cerebral small vessel disease (CSVD) patients and evaluate the value of combination of levels of Aβ40 or Aβ42 and the total CSVD score in predicting VCI.Patients and MethodsA total of 199 CSVD patients were divided into VCI group and non-VCI group according to the criteria of VCI. Demographic data, MRI markers of CSVD, blood pressure, vascular risk factors, laboratory markers, and serum Aβ40 and Aβ42 concentration were collected. Univariate analysis was performed with the Student’s t-test, Mann–Whitney U-test or Chi-square test. Variables with P<0.10 in univariate analysis were then included in multivariate analysis that used a backward stepwise logistic regression model. The predictive values were assessed with receiver operating characteristic (ROC) curve.ResultsVCI was determined in 112 CSVD patients (56.3%). Hyperlipidemia (OR: 1.618, 95% CI: 1.265–3.049), the total CSVD score (OR: 1.414, 95% CI: 1.213–2.278) and serum Aβ42 concentration (OR: 1.401, 95% CI: 1.212–1.946) were independent risk factors for VCI in CSVD patients with adjustment for age, education years, diabetes and fasting blood-glucose (FBG). The area under curves (AUCs) were 0.640 (SE: 0.040, 95% CI: 0.563–0.718), 0.733 (SE: 0.035, 95% CI: 0.664–0.802) and 0.827 (SE: 0.030, 95% CI: 0.768–0.887), respectively, for the total CSVD score, serum Aβ42 concentration and their combination applied in predicting VCI in CSVD patients. Z test demonstrated that the AUC of combination prediction was significantly higher than individual prediction (0.827 vs 0.640, Z=3.740, P<0.001; 0.827 vs 0.733, Z=2.039, P=0.021).ConclusionCombination of Aβ42 and total CSVD score could significantly elevate the predictive value of cognitive impairment in CSVD patients.

Recognition of Cognitive Impairment in Adult Moyamoya Disease: A Classifier Based on High-Order Resting-State Functional Connectivity Network.

Objective: Vascular cognitive impairment (VCI) is a common complication in adult patients with moyamoya disease (MMD), and is reversible by surgical revascularization in its early stage of mild VCI. However, accurate diagnosis of mild VCI is difficult based on neuropsychological examination alone. This study proposed a method of dynamic resting-state functional connectivity (FC) network to recognize global cognitive impairment in MMD.Methods: For MMD, 36 patients with VCI and 43 patients with intact cognition (Non-VCI) were included, as well as 26 normal controls (NCs). Using resting-state fMRI, dynamic low-order FC networks were first constructed with multiple brain regions which were generated through a sliding window approach and correlated in temporal dimension. In order to obtain more information of network interactions along the time, high-order FC networks were established by calculating correlations among each pair of brain regions. Afterwards, a sparse representation-based classifier was constructed to recognize MMD (experiment 1) and its cognitive impairment (experiment 2) with features extracted from both low- and high-order FC networks. Finally, the ten-fold cross-validation strategy was proposed to train and validate the performance of the classifier.Results: The three groups did not differ significantly in demographic features (p > 0.05), while the VCI group exhibited the lowest MMSE scores (p = 0.001). The Non-VCI and NCs groups did not differ significantly in MMSE scores (p = 0.054). As for the classification between MMD and NCs, the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of the classifier reached 90.70, 88.57, 93.67, and 73.08%, respectively. While for the classification between VCI and Non-VCI, the AUC, accuracy, sensitivity, and specificity of the classifier reached 91.02, 84.81, 80.56, and 88.37%, respectively.Conclusion: This study not only develops a promising classifier to recognize VCI in adult MMD in its early stage, but also implies the significance of time-varying properties in dynamic FC networks.

SOLUBLE INTERCELLULAR ADHESION MOLECULE (SICAM-1) AS A BIOMARKER OF VASCULAR COGNITIVE IMPAIRMENT IN OLDER ADULTS

Background: Endothelial dysfunction and subsequent inflammation contribute to the development of vascular cognitive impairment (VCI). Soluble intercellular adhesion molecule-1 (sICAM-1) is upregulated in endothelial dysfunction and promotes an inflammatory response; however, the relationship between sICAM-1 and VCI remains equivocal. Objective: To determine whether sICAM-1 contributes to the prediction of VCI. Methods: Community-dwelling older adults (n=172) from the “Cohort of Obesity, Sarcopenia and Frailty of Older Mexican Adults” (COSFOMA) study were identified as VCI or controls using standard neuropsychological evaluations and neuroimaging. sICAM-1 was quantified using ELISA, and multivariate logistic regression determined the association between sICAM-1 and VCI. Results: 31 VCI cases were identified. sICAM-1 was higher in VCI [VCI: 450.7 (241.6) ng/ml vs. Control: 296.9 (140.9) ng/ml]. sICAM-1 concentrations above the 90th percentile (464.1 ng/mL) was associated with VCI group membership in all models [OR = 6.9 (95% CI: 1.1- 42.2)]. The final saturated model explained 64% of the variance in VCI group membership. Conclusion: High concentrations of sICAM-1 are independently associated with VCI group membership. Efforts to further characterize the relationship between indices of endothelial dysfunction and pathological changes to the aging brain should be further pursued.

Soluble Intercellular Adhesion Molecule-1 (sICAM-1) as a Biomarker of Vascular Cognitive Impairment in Older Adults

Background: Endothelial dysfunction and subsequent inflammation contribute to the development of vascular cognitive impairment (VCI). Soluble intercellular adhesion molecule-1 (sICAM-1) is upregulated in endothelial dysfunction and promotes an inflammatory response; however, the relationship between sICAM-1 and VCI remains equivocal. Objective: To determine whether sICAM-1 contributes to the prediction of VCI. Methods: Community-dwelling older adults (n = 172) from the “Cohort of Obesity, Sarcopenia and Frailty of Older Mexican Adults” (COSFOMA) study were identified as VCI or controls using standard neuropsychological evaluations and neuroimaging. sICAM-1 was quantified using ELISA, and multivariate logistic regression determined the association between sICAM-1 and VCI. Results: A total of 31 VCI cases were identified. sICAM-1 was higher in VCI (VCI: 450.7 [241.6] ng/mL vs. controls: 296.9 [140.9] ng/mL). sICAM-1 concentrations above the 90th percentile (464.1 ng/mL) were associated with VCI group membership in all models (OR: 6.9, 95% CI: 1.1–42.2). The final saturated model explained 64% of the variance in VCI group membership. Conclusion: High concentrations of sICAM-1 are independently associated with VCI group membership. Efforts to further characterize the relationship between indices of endothelial dysfunction and pathological changes to the aging brain should be further pursued.

[Effects of berberine on learning and memory ability in vascular cognitive impairment rats].

To investigate the effects of berberine on learning and memory ability in vascular cognitive impairment rats. Sixty-eight Wistar rats were randomly divided into control group (n=10), sham operated group (n=10) and the modeling group of vascular cognitive impairment rat (n=48), then the rats in modeling group were randomly divided into four groups (n=10): vehicle group, berberine low dose group (20 mg/kg), medium dose group (40 mg/kg) and high dose group (60 mg/kg). Bilateral common carotid arteries were occluded in rats to establish vascular cognitive impairment (VCI) model. Different doses of berberine were intraperitoneally injected into the treatment group and normal saline was intraperitoneally injected into the other groups once a day for a total of 34 days. After 28 days of administration, Morris water maze was used to test the learning and memory ability of rats. After the water maze experiment, the levels of superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha(TNF-α), interleukin-1 beta (IL-1β), 5-hydroxytryptamine (5-HT) and monoamine oxidase (MAO) in the forebrain cortex were detected. Compared to sham group, the escape latency in VCI group was significantly extended (P＜0.01) and the times of passing through the platform were decreased remarkably (P＜0.01). The levels of SOD, GSH and 5-HT in the hippocampus or anterior cortex were decreased significantly (P＜0.01), while the contents of MDA, TNF-α, IL-1β and MAO were increased remarkably (P＜0.01). Compared with VCI group, the escape latency in berberine-treated groups was shortened significantly (P＜0.01, P＜0.05) and the times of passing through the platform were increased remarkably (P＜0.01, P＜0.05), the levels of SOD, GSH and 5-HT were increased significantly (P＜0.01), while the contents of TNF-α, IL-1β and MAO were decreased remarkably (P＜0.01). Berberine could significantly improve the spatial learning and memory abilities of rats with vascular cognitive impairment. The mechanism may be related to the effects of berberine on the hippocampal antioxidant stress, anti-inflammatory response and the monoamine neurotransmitter system in the forebrain cortex. Berberine 60 mg/kg dose group had better effect.

Correlations of serum cystatin C level and gene polymorphism with vascular cognitive impairment after acute cerebral infarction.

The aim of this study was to explore the possible correlations of serum cystatin C level and cystatin C gene (CST3) polymorphism with vascular cognitive impairment in patients who had acute cerebral infarction. A total of 152 patients with acute cerebral infarction were recruited in this case-control study. Patients were divided into vascular cognitive impairment (VCI) group (n = 71) and cognitive impairment no dementia (CIND) group (n = 81). The serum concentrations of cystatin C were measured with immunoturbidimetric assay while the gene polymorphisms of CST3 were determined by technique polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In the VCI group, serum cystatin C level was significantly higher than that in the control group. The frequency of the B allele was found to be higher in the VCI group as compared with that of the CIND group (18.5% vs 7.7%, p = 0.006). In logistic regression analysis, significant associations of VCI with high serum cystatin C level (OR 3.837 (1.176-12.520), p = 0.026) and CST3 B allele (OR 2.038 (1.048-3.963), p = 0.036) were also found. A high cystatin C level and CST3 B allele confer risks for VCI after acute cerebral infarction. It is probable that measurement of the serum cystatin C level and detection of CST3 gene polymorphism would aid in the early diagnosis of VCI, but further studies are warranted.

Study of clinical risk factors and predictors of post stroke vascular cognitive impairment

Introduction: Cognitive impairment due to cerebro vascular disease is termed” vascular cognitive Impairment “(VCI) and forms a spectrum that includes vascular dementia and milder forms of cognitive impairment. Vascular cognitive impairment has some varied and diverse aetiology. This is particularly important as apart from age vascular risk factors, are the most important and presently the only treatable precursor to dementia. This prospective observational study was carried out in indept. Of medicine, GMC Bhopal. Methods: A standard protocol was applied at admission and 3 months after stroke, this protocol included clinical, functional and cognitive assessments, various lab tests and MMSE. Results: Amongst the various risk factors hypertension, diabetes mellitus, prior stroke, dyslipidemia, ischemic heart disease, tobacco chewing, smoking, family history of dementia was more frequently seen in vascular cognitive impairment group. In this study, the frequency of patients having post stroke vascular cognitive impairment (VCI)is 54%. 18%of the patients had VaD (Vascular dementia), 36% of the patients had VMCI(vascular mild cognitive impairment), 46% of the patients had NO VCI (no vascular cognitive impairment. There was significant association of risk factors like Hypertension (p=0.022) diabetes mellitus (P=0.038), dyslipidaemia (p=0.034), prior stroke(p=0.046) with development of vascular cognitive impairment. Post stroke dementia has considerable morbidity. Conclusion: The predictors of development of Vascular cognitive impairment following stroke in this study are lower educational status, Hypertension, Diabetes mellitus, Dyslipidemia, Prior stroke, urinary incontinence, High sys. BP, NIHSS score, LDL level, abnormal ECG, Strategic site lesion and greater severity of age related white matter changes.

Correlation of Stress Hyperglycemia after Ischemic Stroke with Early Vascular Cognitive Impairment.

Objective To investigate the influence and forecast value of stress hyperglycemia on the early vascular cognitive impairment (VCI) in stroke patients.Methods Totally 422 patients with acute non-diabetic stroke were divided into three groups according to the fasting plasma glucose level:the euglycemia group (<6.1 mmol/L),the mild stress hyperglycemia group (6.1-7.0 mmol/L),and the severe stress hyperglycemia group (≥7.0 mmol/L).Mini-mental state examination,Alzheimer's disease rating scale cognitive subscale,and clinical dementia rating scale were used to evaluate early cognition in post-stroke patients,and patients were divided into three groups accordingly:normal cognitive function group,mild VCI group,and vascular dementia group.Correlation analysis was carried out on the level of stress hyperglycemia and the degree of VCI.Results Of these 422 patients,stress hyperglycemia was identified in 62 cases (14.7%).The risk of stress hyperglycemia was higher in patients with a high degree of education [(8.39±3.85)years vs.(6.62±4.39)years,P=0.037)] or a history of cardiovascular disease (45.2% vs.18.3%,P=0.001).VCI was detected in 270 patients (64.0%).Age,sex,smoking,National Institute of Health Stroke Scale score,Hamilton Depression Rating Scale score,stress hyperglycemia,and history of cardiovascular disease were related with early VCI after non-diabetic ischemic stroke (P<0.05).Multivariate Logistic regression analysis showed that stress hyperglycemia was an independent risk factor for VCI in patients with non-diabetic ischemic stroke (OR=3.086,95% CI=1.065-8.929).The risks of cognitive impairment in the mild stress hyperglycemia group and the severe stress hyperglycemia group were higher than that of the euglycemia group,while it was also higher in the severe stress hyperglycemia group than in the mild stress hyperglycemia group (61.11% vs.75.00% vs.90.91%).Stress hyperglycemia was positively correlated with the high risk of early cognitive impairment in stroke patients (rs=0.185,P=0.007).Conclusion There is a significant correlation between stress hyperglycemia and early VCI after ischemic stroke.

The Brief Memory and Executive Test (BMET): A cognitive screening tool to detect and differentiate vascular cognitive impairment and Alzheimer's disease.

While there are several cognitive screening tests available for the detection of cortical dementias such as Alzheimer's disease (AD), these are rarely designed to be sensitive to vascular cognitive impairment (VCI). The Brief Memory and Executive Test (BMET) is a screening measure designed to be sensitive to the cognitive profile of both VCI and AD. This study investigated the ability of the BMET to detect AD, and to differentiate between VCI and AD. This study included 150 patients, with either SVD, both with (n=48) and without VCI (n=51), or AD (N=51) and 51 healthy controls. Participants were aged between 40 and 90years of age and completed both the BMET and the MMSE. Receiver operator characteristic (ROC) curve analysis showed as before the BMET is a good predictor SVD. Additionally, the BMET was a good predictor of AD (AUC=0.96) and performed at least as well as the MMSE (AUC=0.92) when differentiating AD patients from healthy controls. The BMET had a sensitivity of 86% and specificity of 100% for detecting AD patients from control subjects. Using the difference in cognitive profile between the AD and VCI group, we developed an index score which correctly classified 76% of patients as either having VCI or AD. The BMET is a brief and sensitive tool for the detection of cognitive impairment due to both SVD and AD and can be used to aid in the differentiation of the 2 diseases.