Incidence Of Vascular Dementia Research Articles

Nasal Administration of bFGF-Loaded Nanoliposomes Attenuates Neuronal Injury and Cognitive Deficits in Mice with Vascular Dementia Induced by Repeated Cerebral Ischemia‒Reperfusion.

Basic fibroblast growth factor (bFGF) shows great potential for preventing vascular dementia (VD). However, the blood‒brain barrier (BBB) and low bioavailability of bFGF in vivo limit its application. The present study investigated how nasal administration of bFGF-loaded nanoliposomes (bFGF-lips) affects the impaired learning and cognitive function of VD mice and the underlying mechanism involved. A mouse model of VD was established through repeated cerebral ischemia‒reperfusion. A Morris water maze (MWM) and novel object recognition (NOR) tests were performed to assess the learning and cognitive function of the mice. Hematoxylin and eosin (HE) staining, Nissl staining and TUNEL staining were used to evaluate histopathological changes in mice in each group. ELISA and Western blot analysis were used to investigate the molecular mechanism by which bFGF-lips improve VD incidence. Behavioral and histopathological analyses showed that cognitive function was significantly improved in the bFGF-lips group compared to the VD and bFGF groups; in addition, abnormalities and the apoptosis indices of hippocampal neurons were significantly decreased. ELISA and Western blot analysis revealed that bFGF-lips nasal administration significantly increased the concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), bFGF, B-cell lymphoma 2 (Bcl-2), phosphorylated protein kinase B (PAKT), nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1) and haem oxygenase-1 (HO-1) in the hippocampus of bFGF-lips mice compared with the VD and bFGF groups. Furthermore, the concentrations of malondialdehyde (MDA), caspase-3 and B-cell lymphoma 2-associated X (Bax) were clearly lower in the bFGF-lips group than in the VD and bFGF groups. This study confirmed that the nasal administration of bFGF-lips significantly increased bFGF concentrations in the hippocampi of VD mice. bFGF-lips treatment reduced repeated I/R-induced neuronal apoptosis by regulating apoptosis-related protein concentrations and activating the phosphatidylinositol-3-kinase (PI3K)/(AKT)/Nrf2 signaling pathway to inhibit oxidative stress.

Association between aphasia and risk of dementia after stroke

Background and purposeAlthough findings from published studies suggest post-stroke aphasia is associated with an increased risk of dementia, few studies have evaluated its association in a nationally representative cohort with long-term follow-up. No studies have reported data by type of stroke. Therefore, we examined the association between post-stroke aphasia and the risk of developing dementia. MethodsUsing claims data from Taiwan's universal health insurance program, a cohort of patients ≥18 years old with an initial hospitalization for stroke in 2002–2005 were identified and followed up until December 31, 2016. Patients with newly diagnosed aphasia during stroke hospitalization or within 6 months of discharge were defined as the aphasia group. Cox proportional hazards models were used to estimate hazard ratios (HRs) for developing overall, vascular, and non-vascular dementia in patients with and without post-stroke aphasia. ResultsDuring a median follow-up period of 7.9 and 8.6 years for the aphasia (n=17063) and non-aphasia groups (n=105940), respectively, overall dementia incidence was similar, whereas vascular dementia incidence was higher in the aphasia group (7.52 vs. 5.52 per 1000 person-years). The adjusted HRs (95% confidence intervals) were 1.11 (1.06–1.17), 1.42 (1.31–1.53), and 0.94 (0.88–1.01) for overall, vascular, and non-vascular dementia, respectively. The association between aphasia and the risk of vascular dementia did not differ by stroke type (P for interaction=0.43). The analysis of 16856 propensity score-matched pairs revealed similar results. ConclusionPatients with post-stroke aphasia have an increased risk of developing vascular dementia irrespective of the type of stroke.

Ambient air pollution and risk of incident dementia in older men living in a region with relatively low concentrations of pollutants: The Health in Men Study

BackgroundIn areas with moderate to severe air pollution, pollutant concentrations are associated with dementia risk. It is unclear whether the same relationship is present in regions with lower ambient air pollution. ObjectiveTo determine whether exposure to air pollution is associated with risk of incident dementia in general, and Alzheimer's disease and vascular dementia in particular, in older men living in a relatively low ambient air pollution region. MethodsThe cohort comprised 11,243 men residing in Perth, Australia. Participants were aged ≥65 years and free of a dementia diagnosis at time of recruitment in 1996–1999. Incident dementia was identified from recruitment to 2018 via ICD diagnosis codes and subsequent study waves. Concentrations for three air pollutants, nitrogen dioxide (NO2), fine particulate matter less than 2.5 μm in diameter (PM2.5), and black carbon (BC) were estimated at participants’ home addresses using land-use regression models. We used Cox proportional hazards regression models adjusting for smoking status, physical activity, BMI, education, and socio-economic status. ResultsOf 3053 (27.2%) incident cases of dementia, 1670 (54.7%) and 355 (11.6%) had documented Alzheimer's disease and vascular dementia. The average concentration of NO2 was 13.5 (SD 4.4) μg/m3, of PM2.5 was 4.54 (SD 1.6) μg/m3 and of BC was 0.97 (SD 0.29) ×10−5 m−1. None of the air pollutants were associated with incident dementia or Alzheimer's disease. In the unadjusted model, increased exposure to PM2.5 was associated with an increased risk of vascular dementia (for a 5 μg/m3 increase: HR 1.62, 95% CI 1.13, 2.31). However, this association was attenuated following adjustment for confounders (HR 1.39, 95% CI 0.93, 2.08). NO2 and BC were not associated with vascular dementia incidence. DiscussionExposure to air pollution is not associated with increased risk of incident dementia in older men living in a region with relatively low ambient air pollution.

Association of the inflammation-related proteome with dementia development at older age: results from a large, prospective, population-based cohort study

BackgroundChronic inflammation is a central feature of several forms of dementia. However, few details on the associations of blood-based inflammation-related proteins with dementia incidence have been explored yet.MethodsThe Olink Target 96 Inflammation panel was measured in baseline serum samples (collected 07/2000–06/2002) of 1782 older adults from a German, population-based cohort study in a case-cohort design. Logistic regression models were used to assess the associations of biomarkers with all-cause dementia, Alzheimer’s disease, and vascular dementia incidence.ResultsDuring 17 years of follow-up, 504 participants were diagnosed with dementia, including 163 Alzheimer’s disease and 195 vascular dementia cases. After correction for multiple testing, 58 out of 72 tested (80.6%) biomarkers were statistically significantly associated with all-cause dementia, 22 with Alzheimer’s disease, and 33 with vascular dementia incidence. We identified four biomarker clusters, among which the strongest representatives, CX3CL1, EN-RAGE, LAP TGF-beta-1, and VEGF-A, were significantly associated with dementia endpoints independently from other inflammation-related proteins. CX3CL1 (odds ratio [95% confidence interval] per 1 standard deviation increase: 1.41 [1.24–1.60]) and EN-RAGE (1.41 [1.25–1.60]) were associated with all-cause dementia incidence, EN-RAGE (1.51 [1.25–1.83]) and LAP TGF-beta-1 (1.46 [1.21–1.76]) with Alzheimer’s disease incidence, and VEGF-A (1.43 [1.20–1.70]) with vascular dementia incidence. All named associations were stronger among APOE ε4-negative subjects.ConclusionWith this large, population-based cohort study, we show for the first time that the majority of inflammation-related proteins measured in blood samples are associated with total dementia incidence. Future studies should concentrate not only on single biomarkers but also on the complex relationships in biomarker clusters.

The effect of occupation on the incidence of vascular dementia: A 12-year follow-up cohort study

IntroductionVascular dementia (DV) is the second cause of dementia with 15.8-20% of cases. Previous studies of the effect of occupation in DV do not show conclusive results, therefore, the objective was to analyze if the type of occupation can vary the risk of developing DV in those older than 55 years. Material and methodsIn the ZARADEMP project, a community sample of 4,803 individuals were followed longitudinally in four waves. The occupation was classified following the National Classification of Occupations (CNO-11) and the International Standard Classification of Occupations (ISCO-08). Different standardized instruments were used: the medical and psychiatric histories (History and Aetiology Schedule) and other risk factors (Mini-Mental Status Examination, Geriatric Mental State-AGECAT). For this study, we calculated incidence rates, incidence rate ratios and hazard ratios in multivariate Cox regression models, stratified by gender. For this study, we included 3,883 participants. ResultsIn women, the risk of DV was doubled in Blue-collar workers, with a moderate effect (Cohen’s d=0.54) and multiplying by 2.7 in Homeworks respect to White Collar with a moderate effect (Cohen's d=0.77), although they did not reach statistical significance. We did not observe the effect of occupation on the risk of DV in men. ConclusionsWe have found a moderate but non-significant effect between occupation and DV risk in women. We found no effect of occupation on the risk of VD in males while other clinical factors (age, diabetes or body mass index) presented a clearer effect than the occupation.

Long-term low-dose acetylsalicylic use shows protective potential for the development of both vascular dementia and Alzheimer’s disease in patients with coronary heart disease but not in other individuals from the general population: results from two large cohort studies

BackgroundNo population-based cohort study investigated a potential inverse association between long-term low-dose acetylsalicylic acid (ASA) use and all-cause dementia and its two most common sub-types Alzheimer’s disease (AD) and vascular dementia (VD) so far.MethodsCox regression models with inverse probability of treatment weighting to model the underlying cardiovascular risk were used to assess the associations of low-dose ASA use with all-cause dementia, AD, and VD incidence in community-dwelling older adults from the German ESTHER study (N = 5258) and the UK Biobank (N = 305,394). Inclusion criteria were age of 55 years or older and completed drug assessment. Meta-analyses of the individual participant data from the two prospective cohort studies were performed.ResultsFour hundred seventy-six cases of all-cause dementia, 157 cases of AD, and 183 cases of VD were diagnosed over a median of 14.3 years of follow-up in ESTHER. In the UK Biobank, 5584 participants were diagnosed with all-cause dementia, 2029 with AD, and 1437 with VD over a median of 11.6 years. The meta-analysis of both cohorts revealed a weak reduction in hazards for all-cause dementia (hazard ratio (HR) [95% confidence interval (CI)]: 0.96 [0.93 to 0.99]). The strongest protective effect of low-dose ASA was observed in participants with coronary heart disease (CHD) in both cohorts, and a significant interaction was detected. In particular, in meta-analysis, a 31% reduction in hazard for AD, 69% for VD and 34% for all-cause dementia were observed (HR [95% CI]: 0.69 [0.59 to 0.80], 0.31 [0.27 to 0.35], 0.46 [0.42 to 0.50], respectively). Furthermore, compared to non-users, users of low-dose ASA for 10 years or longer (who likely use it because they have CHD or a related diagnosis putting them at an increased risk for cardiovascular events) demonstrated a strong protective effect on all dementia outcomes, especially for VD (HR [95% CI]: 0.48 [0.42 to 0.56]) whereas no protective associations were observed with shorter low-dose ASA use.ConclusionsThe protective potential of low-dose ASA for all-cause dementia, AD, and VD seems to strongly depend on pre-existing CHD and the willingness of patients to take it for a minimum of ten years.

Triad of minimal antenatal care, pre-eclampsia and dementia in rural women: A deep insight and call for awareness.

Pre-eclampsia, a prominent gestational hypertensive disorder, affects around 2-8% of pregnancies and is the dominating cause of late- life maternal morbidities worldwide. Frequent signs of this disorder such as proteinuria, hypertension, and thrombocytopenia, are detected by physicians during the routine antenatal checkups of expectant women. Pre-eclampsia, if left untreated, delineates with complications like central nervous system dysfunction, microangiopathies, thromboembolism, and cerebrovascular accidents in later life of women.[1] Vascular dementia is noticed as one of the late-life complications in women with a history of preeclampsia. Two cohort analyses disclosed a significantly increased risk of vascular dementia in later life of women with a history of preeclampsia. [2,3] Incidence of vascular dementia was noticed as being thrice more common in these women when compared to the non-pre-eclamptic ones. [2] Like all over the world, high percentage of pre-eclampsia cases are also rampant in the rural areas of Pakistan. An analysis from Sukkar, rural Sindh, Pakistan, showed that Preeclampsia and eclampsia cases in a tertiary care hospital accounted for 112 (5.56%) of total 2012 deliveries. Out of these cases, 6.45% were unbooked, depicting the negligence of antenatal care, and 5.8% were found linked to low education levels. [4] The extensive urban-rural gap in the utilization of antenatal care can be determined by the fact that according to reports, 70% of women in the lower quantile of South Asia undergo labor at home in comparison 40% of them deliver without any professional assistance. In Southeast Asia, only 17.7% of lower area women were recorded to use public maternity facilities.[5] A survey from Interior Sindh of Pakistan reported that most rural women have no access to maternity centres within 10km of their living. The authors further stated that the rural residents believed that medical interventions could pose a threat to pregnancy so they preferred untrained midwives over proper maternity centre visits, which could be one of the prime reasons for undiagnosed gestational disorders in these women.[6] Lack of antenatal care utilization could be due to paucity of awareness amongst rural women or the dearth of maternity centres in such underdeveloped areas. Together these factors presented as the key attributes to vascular dementia favouring pre-eclampsia. In rural areas, where barriers to healthcare services and socioeconomic inequality already prevail, this untended rise is a red flag situation. Respective Governments should channel efforts in expanding the accessible maternity setups in these poorly facilitated areas. --Continue

Inflammation biomarkers for future development of all‐cause dementia, Alzheimer's disease, and vascular dementia

AbstractBackgroundInflammation is one of the key mechanisms involved in the development and progression of dementia. However, not all details on the association between inflammation and dementia have been explored yet. Inflammatory biomarkers can be measured at an early stage of dementia and thus can contribute to an early diagnosis. Besides, these biomarkers could contribute to drug development or therapeutic strategies.MethodBiomarkers from the Olink Proseek® Inflammation panel were analyzed in blood samples of a longitudinal German, population‐based cohort including 1782 older adults. Logistic regression models were used to identify associations of these biomarkers with all‐cause dementia, Alzheimer's disease (AD), and vascular dementia (VD) incidence. Strongly associated biomarkers were further analyzed in subgroup and sensitivity analyses for dementia risk factors like age, diabetes, and APOE ε4 polymorphism. Moreover, clusters including highly correlated biomarkers (r > 0.5) were built based on these biomarkers.ResultDuring 17 years of follow‐up, 504 participants were diagnosed with dementia, including 163 AD and 195 VD cases. A total number of 56 biomarkers showed a significant association with all‐cause dementia, 22 biomarkers were significantly associated with AD, and 33 with VD incidence, even after correction for multiple testing. The strongest, independent associations were found for the biomarkers CX3CL1 (OR [95% CI] per 1 standard deviation (SD): 1.41 [1.24‐1.60]) and EN‐RAGE (1.41 [1.25‐1.60]) with all‐cause dementia incidence, EN‐RAGE (1.51 [1.25‐1.83]) and LAP TGF‐beta‐1 (1.46 [1.21‐1.76]) with AD incidence, and VEGF‐A (1.43 [1.20‐1.70]) with VD incidence.ConclusionThis study was the first to assess the associations of blood‐based biomarkers from the Olink Proseek® Inflammation panel with all‐cause dementia, AD, and VD incidence in a large, prospective, population‐based cohort study. The biomarkers CX3CL1, EN‐RAGE, LAP TGF‐beta‐1, and VEGF‐A, were independently associated with different forms of dementia and have great potential as predictive biomarkers.

Analysis of the Characteristics and Related Risk Factors of Vascular Dementia After Ischemic Stroke Based on Nuclear Magnetic Resonance

VD (Vascular Dementia) refers to clinical dementia caused by brain tissue damage caused by cerebrovascular disease factors. It is one of the common types of dementia. This paper examines patients with first stroke to determine whether to list them as observation objects and randomly divides the observation objects into intervention groups and control groups. Studies have shown that the incidence of VD after a stroke is closely related to the location of the stroke, and the incidence of VD in the intervention group is significantly lower than that in the control group. In addition, there were no significant adverse reactions in the intervention group. In this paper, 51 patients with VD after cerebral infarction were selected as the VD group, and 48 patients with non-VD after cerebral infarction were selected as the non-VD group. All 99 patients with stroke were assessed for cognitive function using the simple mental scale and the Montreal Cognitive Assessment Scale within 3 months after stroke. The characteristics of skull MRI (Magnetic Resonance Imaging) and related risk factors in patients with VD and non-VD were compared and analyzed. The results showed that age, hypertension, and diabetes were associated with the occurrence of VD.

Epidemiological aspects of vascular dementia in the Northwestern Federal District in 2010-2019

Study design is descriptive epidemiological. We analyzed the data of 11 entities that are part of the North-West Federal District, including in comparison with general indicators for the Russian Federation. There was an increase in the prevalence and a decrease in the incidence of vascular dementia in 2019 compared to 2010. In the Northwestern Federal District, both indicators were higher than all-Russian ones. A small number of cases of vascular dementia can be observed at a young age, but its exponential growth is observed after 60 years. Among previously ill vascular dementia and newly diagnosed, there is an almost twofold predominance of women. The results can be used in solving issues of the organization of psychiatric care and developing prevention algorithms for vascular dementia.

Incident Dementia in Elderly Patients with Nonalcoholic Fatty Liver Disease in Germany

Dementia and NAFLD are two frequent conditions that share underlying risk factors mainly in the realm of metabolic disease. Additionally, an association between NAFLD and brain aging has been proposed. Therefore, we investigated the hypothesis if NAFLD is an independent risk factor for emerging dementia. In this population-based cohort study, elderly patients (≥ 65 years) with NAFLD diagnosed between 2000 and 2015 were matched 1:1 to a cohort without NAFLD based on ICD-10 coding in the Disease Analyzer database. Matching criteria were age, sex, physician, index year, and co-diagnoses associated with dementia. The primary outcomes of this study were all-cause dementia diagnoses, the incidence of vascular dementia, and antidementive drug prescription. A total of 22,317 patients with NAFLD were matched to 22,317 patients without NAFLD. Within 10 years of the index date, 16.0% of patients with NAFLD and 15.6% of the patients without NAFLD were diagnosed with dementia. On Cox regression analysis, there is no association between NAFLD and the incidence of all-cause dementia (HR 0.97, 95% CI 0.92–1.04), vascular dementia (HR 0.89, 95% CI 0.78–1.02), or the new prescription of antidementive therapy (HR 0.87, 95% CI 0.76–1.01). In sensitivity analyses, there was no association between NAFLD and dementia in different age-groups as well as men or women. In conclusion, in this database study of elderly patients coded with NAFLD no independent association with incident dementia was detected. Risk assessment regarding dementia in patients with NAFLD should be carried out in the same way as for metabolic burdened patients.

Association between Anxiety and Vascular Dementia Risk: New Evidence and an Updated Meta-Analysis.

The association between anxiety and vascular dementia (VaD) is unclear. We aimed to reliably estimate the association between anxiety and VaD risk using meta-analysis to pool new results from a large community-based cohort (Zaragoza Dementia and Depression (ZARADEMP) study) and results from previous studies. ZARADEMP participants (n = 4057) free of dementia were followed up on for up to 12 years. Cases and subcases of anxiety were determined at baseline. A panel of four psychiatrists diagnosed incident cases of VaD by consensus. We searched for similar studies published up to October 2019 using PubMed and Web of Science. Observational studies reporting associations between anxiety and VaD risk, and adjusting at least for age, were selected. Odds ratios (ORs) from each study were combined using fixed-effects models. In the ZARADEMP study, the risk of VaD was 1.41 times higher among individuals with anxiety (95% CI: 0.75–2.68) compared with non-cases (p = 0.288). Pooling this result with results from two previous studies yielded an OR of 1.65 (95% CI: 1.07–2.53; p = 0.022). These findings indicate that anxiety is associated with an increased risk of VaD. Taking into account that anxiety is commonly observed in the elderly, treating and preventing it might reduce the prevalence and incidence of VaD. However, whether anxiety is a cause of a prodrome of VaD is still unknown, and future research is needed to clarify this.

Associations of urinary 8-iso-prostaglandin F2α levels with all-cause dementia, Alzheimer's disease, and vascular dementia incidence: results from a prospective cohort study.

Prospective studies on a potential association of 8-iso-prostaglandin F2α (8-iso-PGF2α ) levels, a biomarker of lipid peroxidation, with dementia are limited. Multivariate Cox regression models were used to assess potential associations of urinary 8-iso-PGF2α levels with all-cause, Alzheimer's disease (AD), and vascular dementia (VD) incidence in 5853 older adults from a German, population-based cohort. Over 14 years of follow-up, 365 all-cause dementia cases including 127 VD and 109 AD cases were diagnosed. Participants in the top compared to the bottom 8-iso-PGF2α tertile had a 45% increased risk of all-cause dementia incidence (hazard ratio [95% confidence interval]: 1.45 [1.12 to 1.88]). Interaction with the apolipoprotein E (APOE) ԑ4/ԑ4 genotype was detected (P = .02). Furthermore, continuously modeled, logarithmized 8-iso-PGF2α levels were statistically significantly associated with all-cause dementia and AD incidence. Oxidative stress may be involved in the pathogenesis of dementia. Individuals with increased 8-iso-PGF2α levels and the APOE ԑ4/ԑ4 genotype showed a considerably increased dementia risk.

Variability in Total Cholesterol Concentration Is Associated With the Risk of Dementia: A Nationwide Population-Based Cohort Study.

Introduction: Although total cholesterol (TC) variability is suggested as a risk factor for cardiovascular and cerebrovascular disease, there is no previous study to evaluate the association between TC variability and the development of dementia.Methods: Using the Korean National Health Insurance Service–Health Screening Cohort (NHIS-HEALS), the main outcomes were newly diagnosed all-cause dementia, Alzheimer's disease (AD), or vascular dementia (VaD) between January 1, 2008, and December 31, 2015. Visit-to-visit TC variability was measured as variability independent of the mean (TC-VIM), coefficient variance (TC-CV), and standard deviation (TC-SD).Results: In a total of 131,965 Koreans, there were 3,722 all-cause dementia (2.82%), 2,776 AD (2.10%), and 488 VaD (0.37%) during the median follow-up of 8.4 years. Kaplan–Meier curves showed increased cumulative incidences for all in the group of the highest quartiles of TC variability compared to the others. Regression using the Fine and Gray hazards model showed a steadily increasing risk of all-cause dementia with higher quartiles of TC variability. After adjusting for confounders including mean TC level and comparing the highest and lowest TC-VIM quartiles, the hazard ratios (HRs) for all-cause dementia and AD were 1.15 [95% confidence interval (CI) = 1.05–1.27; P = 0.003] and 1.12 (95% CI = 1.00–1.25; P = 0.040), respectively. The incidence of VaD was not significantly higher in the higher-quartile groups compared to that in the lowest-quartile group in TC-VIM variability (HR 1.22; 95% CI = 0.95–1.59; P = 0.122). These associations were consistent with TC variability defined by TC-CV or TC-SD.Conclusions: For the first time, we have demonstrated that a higher visit-to-visit variability in TC independent of mean TC is associated with an increased risk of all-cause dementia and AD in the general population.

IL-10 targets Th1/Th2 balance in vascular dementia.

The pathogenesis of vascular dementia (VD) is not fully elucidated. Th1/Th2 balance may change in VD, leading to numerous inflammatory cytokines secretion. Interleukin-10 (IL-10) is an immune suppressor, while its function in VD and correlation with Th1/Th2 balance are still unclear. The healthy male rats were randomly divided into three groups, including sham group, model group, and IL-10 group. Th1 and Th2 cytokines IL-2, IL-4, IL-6, and tumor necrosis factor-α (TNF-α) expressions in the serum were tested by enzyme-linked immunosorbent assay (ELISA). IL-10 expression in brain tissue and peripheral blood was detected by Real-Time PCR and ELISA. The correlation relationship between IL-10 and T helper cells 1/2 (Th1/Th2) cytokines was analyzed. Hippocampus cell apoptosis was determined by caspase 3 activity kit. Nuclear transcription factor 2 κB (NF-κB) expression was evaluated by Western blot. IL-10 levels were decreased, caspase 3 activity was enhanced, NF-κB expression was declined, IL-2 and TNF-α secretion were up-regulated, while IL-4 and IL-6 secretion were reduced in hippocampus tissue and peripheral blood from VD model rat compared to sham group (p<0.05). IL-10 significantly attenuated caspase 3 activity, up-regulated NF-κB expression, reduced IL-2 and TNF-α secretion, and enhanced IL-4 and IL-6 secretion (p<0.05). IL-10 was negatively correlated with Th1 cytokines and positively correlated with Th2 cytokines (p<0.05). IL-10 expression declined in VD and participated in regulating Th1/Th2 balance. IL-10 participated in VD incidence and development through regulating cell apoptosis and NF-κB expression.

Mitochondrial factor and cell cytokines associate with TCM syndrome scale in vascular dementia patients.

Mitochondrial factor and cell cytokines play important roles in the incidence of vascular dementia (VD), but their correlations with inflammatory and mitochondrial factors and the role of both in the kidney essence deficiency pattern and phlegm turbidity blocking orifice pattern are not clear. This study was aimed at studying the correlations between the serum mitochondrial factor and cell cytokines with TCM Syndrome Scale in vascular dementia. According to the inclusion criteria we collected 108 vascular dementia patients which were divided into the kidney essence deficiency pattern and phlegm turbidity blocking orifice pattern based on the TCM Syndrome Scale. We measured serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) concentration using an enzyme-linked immunosorbent assay (ELISA) and serum malondialdelyde (MDA) and superoxide dismutase (SOD) was quantified according to instructions of kits from the 108 patients (45 in kidney essence deficiency pattern, 63 in phlegm turbidity blocking orifice pattern). The scale scores were assessed using TCM Syndrome Scale, MMSE, Hachinski, Barthel, BBS, CDR. There was a significant difference on the scores of CDR and the factors of the memory, judgment, social affairs, personal care, family and hobbies among the two groups, The means of kidney essence deficiency group was higher than that of phlegm turbidity blocking orifice pattern group. IL-18 and SOD in the phlegm turbidity blocking orifice group was higher than those in the kidney essence deficiency pattern; IL-6 in phlegm turbidity blocking orifice pattern group was lower than that in the kidney essence deficiency pattern. By logistic regression analysis, we demonstrated that high concentration of IL-6, TNF-α, and MDA were associated with increased TCM syndrome scores in two groups, while IL-6, IL-18, TNF-α, SOD were associated with decreased MMSE, Barthel. Our study support the notion that IL-6 plays a more important role in the integral of kidney essence deficiency pattern, IL-18 is a more important factor in phlegm turbidity blocking orifice pattern. The results can be used as the theoretical basis of traditional Chinese Medicine prescription and pharmacological research in future, through decrease in IL-6 lever and increase in SOD in integral kidney essence deficiency pattern, and IL-18 as the main anti inflammation index in phlegm turbidity blocking orifice pattern.

Cerebrolysin alleviates cognitive deficits induced by chronic cerebral hypoperfusion by increasing the levels of plasticity-related proteins and decreasing the levels of apoptosis-related proteins in the rat hippocampus

The incidence of vascular dementia (VaD) has rapidly increased over the past few decades. Although officially approved medications for VaD remain limited, cerebrolysin (CBL) had preventive and treatment effects on VaD in some clinical trials. However, the underlying mechanisms have not been determined. The aim of this study was to determine whether CBL protects against cognitive deficits in a rat model of VaD induced by chronic cerebral hypoperfusion by increasing the levels of plasticity-related proteins and decreasing the levels of apoptosis-related proteins. In our study, adult male Sprague-Dawley rats were subjected to bilateral common carotid artery occlusion (BCCAO) surgery. The animals were randomly divided into four groups after the operation: Sham, Vehicle, L-CBL (2.5ml/kg), and H-CBL (5ml/kg). CBL was administered after the operation daily for 28 days. The CBL treatment significantly decreased the escape latency and increased the percentage of time the rat spent in the target quadrant of the Morris water maze (MWM) task. Pathological changes in the hippocampus, such as reduced cell count numbers and obvious pyknosis, were observed using haematoxylin–eosin (HE) staining. Furthermore, CBL significantly increased the expression of plasticity-related synaptic proteins, such as postsynaptic density protein 95 (PSD-95), protein kinase C subunit gamma (PKCγ), phosphorylated cAMP response element binding protein (p-CREB), and decreased the expression of apoptosis-related proteins in the hippocampus. In summary, CBL likely protects against cognitive deficits by improving synaptic plasticity and decreasing apoptosis.

Dl-3-n-butylphthalide can improve the cognitive function of patients with acute ischemic stroke: a prospective intervention study

Objectives: The present study investigated the effects of dl-3-n-butylphthalide on cognitive function of patients with acute ischemic stroke (AIS).Methods: A total of 104 patients with AIS admitted between October 2012 and June 2013 were assigned to either the Treatment (standardized treatment plus dl-3-n-butylphthalide) or Control (standardized treatment alone) groups. Cognitive function was assessed by the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ) and Mini-Mental State Examination (MMSE) before and 1 month after treatment, when high-sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy) were also detected. A multivariate logistic regression analysis was done for explore the independent risk factors for vascular dementia (VD).Results: The proportion of cognitive impairment was significantly lower after treatment than before in both the Treatment (88% vs. 64%, P = 0.023) and Control (87% vs. 70%, P = 0.047) groups. Vascular dementia dropped from 30 to 10% in the Treatment (P = 0.035) and from 25.9 to 16.7% in the Control (P = 0.027) groups. Total cognitive improvement was more significant in the Treatment Group (P = 0.018); naming, memory, attention, and linguistic abilities were significantly improved (all P < 0.05). Serum Hcy and hs-CRP levels were significantly lower in the Treatment Group than in the Control Group 1 month after treatment (P < 0.05).Discussion: Dl-3-n-butylphthalide could significantly improve the cognitive function of AIS patients 1 month after stroke. Hcy was involved in the incidence of VD 1 month after AIS. However, further studies are necessary because of differences between groups at baseline.

Bee Venom Ameliorates Cognitive Dysfunction Caused by Neuroinflammation in an Animal Model of Vascular Dementia.

Vascular dementia (VaD) is caused by the reduction of blood supply by vessel occlusion and is characterized by progressive cognitive decline. VaD incidence has been growing due to the aging population, placing greater strain on social and economic resources. However, the pathological mechanisms underlying VaD remain unclear. Many studies have used the bilateral common carotid artery occlusion (BCCAO) animal model to investigate potential therapeutics for VaD. In this study, we investigated whether bee venom (BV) improves cognitive function and reduces neuroinflammation in the hippocampus of BCCAO animals. Animals were randomly divided into three groups: a sham group (n=15), BCCAO control group (n=15), and BV-treated BCCAO group (n=15). BCCAO animals were treated with 0.1μg/g BV at ST36 ("Joksamli" acupoint) four times every other day. In order to investigate the effect of BV treatment on cognitive function, we performed a Y-maze test. In order to uncover any potential relationship between these results and neuroinflammation, we also performed Western blotting in the BCCAO group. Animals that had been treated with BV showed an improved cognitive function and a reduced expression of neuroinflammatory proteins in the hippocampus, including Iba-1, TLR4, CD14, and TNF-α. Furthermore, we demonstrated that BV treatment increased pERK and BDNF in the hippocampus. The present study thus underlines the neuroprotective effect of BV treatment against BCCAO-induced cognitive impairment and neuroinflammation. Our findings suggest that BV may be an effective complementary treatment for VaD, as it may improve cognitive function and attenuate neuroinflammation associated with dementia.

Renin–angiotensin system-targeting antihypertensive drugs and risk of vascular cognitive impairment: A meta-analysis

ObjectivesTo evaluate the effects of renin–angiotensin system (RAS)-targeting antihypertensive drugs and its classes on the incidence of vascular cognitive impairment (VCI). MethodsPubmed, Embase, and Cochrane Library database of selected articles, and previous systematic reviews through May 2015 were searched. Studies that evaluated the association between use of RAS-targeting drugs and VCI were included. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using fixed effects models or random effects models. ResultsIn all studies as a whole, the use of RAS-targeting drugs was significantly associated with a reduced risk of VCI (RR, 0.87; 95% CI, 0.75–0.98) and vascular dementia (VD) (RR, 0.78; 95% CI, 0.64–0.93), compared no use of RAS-targeting drugs. Subgroup analysis showed that subjects with Angiotensin-Converting Enzyme Inhibitors (ACEI) use significantly associated with a reduced incidence of VCI (RR, 0.81; 95% CI 0.70–0.91) and VD (RR, 0.75; 95% CI, 0.57–0.93); however, subjects with Angiotensin Receptor Blockers (ARB) use had not this effect on VCI (RR, 0.94; 95% CI 0.76–1.13) or VD (RR, 0.94; 95% CI, 0.45–1.44). In an analysis of subgroups, case-control studies found that the use of RAS-targeting drugs could effectively decrease the incidence of VCI (RR, 0.77; 95% CI 0.66–0.87) and VD (RR, 0.77; 95% CI, 0.66–0.88); however, the randomized trials alone showed no significant effect on the incidence of VCI (RR, 0.94; 95% CI 0.82–1.07) or VD (RR, 0.94; 95% CI, 0.35–1.53). Meanwhile, in an analysis of cognitive impairment of vascular origin (VaCI), no significant association was found between RAS-targeting drugs, ACEI, or ARB and the incidence of VaCI. ConclusionRAS-targeting drugs treatment may produce remarkable efficacy on reducing the incidence of VCI and VD. Meanwhile, ACEI use, rather than ARB use, significantly protects against VCI and VD incidence. However, among the classes of RAS-targeting drugs, neither ACEI nor ARB plays protective role in VaCI incidence. Further more RCTs are required to reliably establish whether RAS-targeting drugs use decreases the risk of VCI (VD and VaCI).