Vascular Dementia Group Research Articles

Changes in choroidal thickness quantified by Optical Coherence Tomography across cognitive impairment: data from the NORFACE cohort.

Optical coherence tomography (OCT) enables high-resolution imaging of ocular structures in health and disease. Choroid thickness (CT) is a key vascular retinal parameter that can be assessed by OCT and might be relevant in the evaluation of the vascular component of cognitive decline. We aimed to investigate CT changes in a large cohort of individuals cognitive unimpaired (CU), with mild cognitive impairment due to Alzheimer's (MCI-AD), mild cognitive impairment due to cerebrovascular disease (MCI-Va), Alzheimer's disease dementia (ADD), and vascular dementia (VaD). Clinical, demographical, ophthalmological and OCT data from the Neuro-ophthalmological Research at Fundació ACE (NORFACE) project were analyzed. CT was assessed in the macula across nine Early Treatment Diabetic Retinopathy Study (ETDRS) quadrants, average thickness, total volume, and subfoveal choroidal thickness. Differences of CT among the five diagnostic groups were assessed in a multivariate regression model, adjusting for demographic and cardiovascular risk factors and OCT image quality. A comparison between manual and automatic CT measurements in a subset of participants was also performed. The study cohort comprised 1,280 participants: 301 CU, 196 MCI-AD, 112 MCI-Va, 578 ADD, and 93 VaD. CT was significantly increased in individuals with cognitive impairment compared to those CU, particularly in the VaD and MCI-Va groups and in the peripheral ETDRS regions. No significant differences were found in inner superior, center and subfoveal choroidal thickness. The interaction of sex and diagnosis had no effect in differentiating CT. Mini-Mental State Examination (MMSE) scores were not correlated to CT. Manual and automated CT measurements showed good reliability. Our findings indicated that peripheral choroidal thickening, especially in patients with cerebrovascular disease, may serve as a potential choroidal biomarker for cognitive decline and suggest different pathogenic pathways in AD and VaD. Further research is required to explore CT as a reliable ocular biomarker for cognitive impairment.

Role of BIX01294 in the intracranial inhibition of H3K9 methylation lessens neuronal loss in vascular dementia model.

Dementia develops as a result of multiple factors, including cerebrovascular disease which is called vascular dementia (VD). Histone-3 lysine-9 dimethylation (H3K9me2) broadly increases during VD and inhibits neuroprotective gene expressions. So, we aimed to determine how H3K9me2 inhibitor (BIX01294) affects neuronal damage in VD. An in vivo model of VD was used followed by BIX01294 treatment. Behavioral tests, hematoxylin, and eosin (H&E), Congo red, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were carried out. Hippocampal phosphorylated cyclic-AMP responsive element binding protein (p-CREB), c-fos, brain-derived neurotrophic factor (BDNF), and H3K9me2, were detected by western blot analysis technique. Neurological deficit and anxiety-related behavior significantly reduced in the treatment group compared to the VD group (p < 0.05). BIX01294 improved spatial and passive avoidance memory (p < 0.01 and p < 0.05, respectively) compared to the VD group. Treatment with BIX01294 restored the level of p-CREB/CREB ratio (p < 0.05), cfos (p < 0.01), BDNF (p < 0.01), and suppressed H3K9me2 (p < 0.001) when compared to the VD group. BIX01294 microinjection reduced the apoptosis level in TUNEL staining (p < 0.05), and raised neural cell count in H&E staining (p < 0.01); amyloid beta accumulation significantly decreased in the treatment group (p < 0.05) compared to the VD group. In conclusion, long-term treatment with a low dose of BIX01294 can prevent the progression of neuronal loss in VD model by raising the expression of neurotrophic factors, and reducing the apoptosis level.

Distribution of neuropsychiatric profiles and comorbid diseases in dementia subtypes

Objectives: Alzheimer’s disease (AH) is the most prevalent cause of dementia, followed closely by vascular dementia. Mixed vascular-Alzheimer’s dementia (MVAD) is more evident in individuals aged 80 and above. Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after AH. Vascular risk factors play important role in the pathogenesis of dementia syndromes. Behavioral and psychological symptoms represent a significant portion of the non-cognitive manifestations in dementia patients. This study aimed to evaluate the distribution of chronic diseases, behavioral disorders, psychiatric findings, and medication use in patients followed with different dementia diagnoses. Methods: Prevalance of chronic diseases, behavioral disorders, psychiatric findings as well as the usage of antidepressant and antipsychotic medications among patients followed up in dementia outpatient clinics with the diagnosis of AD, mild cognitive impairment (MCI), vascular dementia (VaD), FTD, and MVAD were investigated. Neuropsychiatric inventory (NPI) was applied to the patients. Results: Four hundred and fifty-five patients were accepted in the study. The patients were distributed as follows: AD (n=303, female/male: 187/115, age = 78±8 years), MCI (n=53, female/male: 31/22, age = 69±10 years), VaD (n=31, female/male: 18/13, age = 68±9 years), FTD (n=32, female/male: 17/15, age = 68±9 years), and MVAD (n=36, female/male: 16/20, age = 76±10 years). Both AD and MVAD groups were significantly older than the other groups (F = 23.2, P&amp;lt;0.0001). The ratio of comorbid chronic diseases was 80% in the AD group, 72% in the MCI group, 91% in the VaD group, 59% in the FTD group, and 93% in the MVAD group. In the whole group, antipsychotic drug use was 27.5% and antidepressant drug use was 28.9%. The mean NPI score was 32.9±28 in antipsychotic users and 16±19 in non-users (P&amp;lt;0.0001). The mean NPI of antidepressant users was 17.6±19 and 21.9±25 (P=0.055) in non-users. Conclusion: There is a comorbid chronic disease burden in all dementia subtypes, although at varying intensities, and as the chronic disease burden increases, behavioral disorders and psychotic findings increase, and accordingly, the use of antipsychotics also increases.

Treadmill exercise prevents recognition memory impairment in VD rat model and enhancement of hippocampal structural synaptic plasticity.

In vascular dementia (VD), memory impairment caused by the damage of synaptic plasticity is the most prominent feature that afflicts patients and their families. Treadmill exercise has proven beneficial for memory by enhancing synaptic plasticity in animal models including stroke, dementia, and mental disorders. The aim of this study was to examine the effects of treadmill exercise on recognition memory and structural synaptic plasticity in VD rat model. Male Sprague-Dawley rats were randomly assigned into four groups: control group (C group, n=6), vascular dementia group (VD group, n=6), treadmill exercise and vascular dementia group (Exe-VD group, n=6), and treadmill exercise group (Exe group, n=6). Four-week treadmill exercise was performed in the Exe-VD and Exe groups. Then, the common carotid arteries of rats in the VD and Exe-VD groups were identified to establish the VD model. Behavior tests (open-field test and novel recognition memory test) were adopted to evaluate anxiety-like behavior and recognition memory. Transmission electron microscopy and Golgi staining were performed to observe synaptic ultrastructure and spine density in the hippocampus. Our study demonstrated that VD rat exhibited significantly anxiety-like behavior and recognition impairment (p <.01), while treadmill exercise significantly alleviated anxiety-like behavior and improved recognition memory in VD rat (p <.01). Transmission electron microscopy revealed that hippocampal synapse numbers were significantly decreased in the VD group compared to the control group (p <.05). These alterations were reversed by treadmill exercise, and the rats exhibited healthier synaptic ultrastructure, including significantly increased synapse (p <.05). Meanwhile, golgi staining revealed that the spine numbers of the hippocampus were significantly decreased in the VD group compared to the control group (p <.05). When compared with the VD group, hippocampal spine numbers were significantly increased in the Exe-VD group (p <.05). The improvement of VD-associated recognition memory by treadmill exercises is associated with enhanced structural synaptic plasticity in VD rat model.

Influence of Behavioral and Psychological Symptoms on Caregiver Burden for Different Types of Dementia: Clinical Experience in Lima, Peru

Introduction: People caring for patients with dementia are prone to suffering from burden. Behavioral and psychological symptoms of dementia (BPSD) may have an impact on caregiver burden. In Latin American countries, there is a lack of research on caregiver burden. We aimed to determine which BPSD have the greatest impact on caregiver burden among Peruvian patients with dementia and to compare the effects of BPSD on caregiver burden across different types of dementia. Methods: A cross-sectional study was conducted on 231 patients living with Alzheimer’s dementia (AD), behavioral variant frontotemporal dementia (bvFTD), dementia with Lewy bodies (DLB), and vascular dementia (VD) and their caregivers who attended a Peruvian memory clinic. BPSD were assessed with the Neuropsychiatric Inventory (NPI). Caregiver burden was assessed with the Zarit Burden Inventory. We used analysis of variance to compare the AD, bvFTD, DLB, and VD groups. Correlations between Zarit Burden Inventory and NPI subscale scores were assessed with Spearman’s correlation. Results: DLB caregivers had significantly higher levels of burden than the other patient groups (p < 0.05) and higher total NPI scores than caregivers for other patient groups (p < 0.05). bvFTD caregivers had significantly higher total NPI scores than AD and VD caregivers (p < 0.05). Hallucinations, aberrant motor behavior, and apathy were the symptoms most significantly correlated with caregiver burden in those caring for DLB, bvFTD, and AD patients, respectively. Conclusion: Neuropsychiatric symptoms are higher in DLB caregivers. Hallucinations, aberrant motor behavior, and apathy are the main symptoms correlated with burden.

Evaluation of Peripheral Inflammatory Activity in Different Types of Dementia

Aim: Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by pathophysiological processes involving neuroinflammation, neurodegeneration, and synaptic dysfunction. Vascular dementia (VaD) stands as the second most prevalent form among all dementia types, sharing common pathophysiological mechanisms with AD, such as vascular oxidative stress and chronic inflammation.The neutrophil-to-lymphocyte ratio (NLR) is considered a simple, noninvasive, and widely available clinical marker of inflammation. The aim of this study is to investigate the potential differences between these two different types of dementia in terms of NLR values. Materials and Methods:The data of patients diagnosed with AD or VaD and healthy controls who applied to a University Hospital Neurology outpatient clinic were retrospectively examined, and the groups were analyzed with statistical methods in terms of NLR levels. Results: A total of 39 AD, 32 VaD, and 30 healthy controls were enrolled in the study. Hemogram analyses revealed significantly elevated NLR values in both the AD and VaD groups compared to the healthy control group (p = .001, p = .001, respectively). AD and VaD groups demonstrated no significant difference in NLR (p = .787).Additionally, as a result of regression analyses, it was determined that age and NLR were independent variables associated with the presence of dementia. Conclusions:NLR values are at higher levels in AD and VaD patient groups compared to healthy controls. Our results support the role of peripheral inflammation in the pathogenesis of VaD, as in AD. Additional studies are needed on potential inflammatory biomarkers of VaD.

Vascular endothelial growth factor is an effective biomarker for vascular dementia, not for Alzheimer's disease: A meta-analysis.

Vascular pathology is known to contribute to dementia and vascular endothelial growth factor (VEGF) is a well-established biomarker associated with vascular alterations. Nonetheless, research findings on VEGF in Alzheimer's disease (AD) and vascular dementia (VaD) are inconsistent across various studies. We conducted a meta-analysis to elucidate relationships between VEGF and AD/VaD. Twenty-four studies were included. Pooled data showed that both blood and cerebrospinal fluid (CSF) VEGF levels were higher in VaD patients, whereas no significant difference was found between AD patients and healthy controls. However, the correlation between blood VEGF and AD was found among studies with AD pathology verification. And blood VEGF levels were higher in AD patients than controls in "age difference<5 years" subgroup and CSF samples for European cohorts. This study highlights that VEGF is more effective for the diagnosis of VaD and vascular factors are also an important contributor in AD. Vascular endothelial growth factor (VEGF) levels were higher in the vascular dementia group, but not in the overall Alzheimer's disease (AD) group.Correlation between VEGF and AD was found among studies with clear AD pathological verification.Elevated VEGF in the cerebrospinal fluid might be a diagnostic marker for AD in European populations.

Treadmill exercise pretreatment ameliorated structural synaptic plasticity impairments of medial prefrontal cortex in vascular dementia rat and improved recognition memory

This study aimed to investigate structural synaptic plasticity in the medial prefrontal cortex of rats under treadmill exercise pretreatment or naive conditions in a vascular dementia model, followed by recognition memory performance in a novel object recognition task. In this study, 24 Sprague–Dawley rats were obtained and randomly assigned into 4 groups as follows: control group (Con group, n = 6), vascular dementia (VD group, n = 6), exercise and vascular dementia group (Exe + VD group, n = 6), and exercise group (Exe group, n = 6). Initially, 4 weeks of treadmill exercise intervention was administered to the rats in the Exe + VD and Exe groups. Then, to establish the vascular dementia model, the rats both in the VD and Exe + VD groups were subjected to bilateral common carotids arteries surgery. One week later, open-field task and novel recognition memory task were adopted to evaluate anxiety-like behavior and recognition memory in each group. Then, immunofluorescence and Golgi staining were used to evaluate neuronal number and spine density in the rat medial prefrontal cortex. Transmission electron microscopy was used to observe the synaptic ultrastructure. Finally, microdialysis coupled with high-performance liquid chromatography was used to assess the levels of 5-HT and dopamine in the medial prefrontal cortex. The behavior results showed that 4 weeks of treadmill exercise pretreatment significantly alleviated recognition memory impairment and anxiety-like behavior in VD rats (P < 0.01), while the rats in VD group exhibited impaired recognition memory and anxiety-like behavior when compared with the Con group (P < 0.001). Additionally, NeuN immunostaining results revealed a significant decrease of NeuN-marked neuron in the VD group compared to Con group (P < 0.01), but a significantly increase in this molecular marker was found in the Exe + VD group compared to the Con group (P < 0.01). Golgi staining results showed that the medial prefrontal cortex neurons in the VD group displayed fewer dendritic spines than those in the Con group (P < 0.01), and there were more spines on the dendrites of medial prefrontal cortex cells in Exe + VD rats than in VD rats (P < 0.01). Transmission electron microscopy further revealed that there was a significant reduction of synapses intensity in the medial prefrontal cortex of rats in the VD group when compared with the Con group(P < 0.01), but physical exercise was found to significantly increased synapses intensity in the VD model (P < 0.01). Lastly, the levels of dopamine and 5-HT in the medial prefrontal cortex of rats in the VD group was significantly lower compared to the Con group (P < 0.01), and treadmill exercise was shown to significantly increased the levels of dopamine and 5-HT in the VD rats (P < 0.05). Treadmill exercise pretreatment ameliorated structural synaptic plasticity impairments of medial prefrontal cortex in VD rat and improved recognition memory.

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.

Iron and risk of dementia: Mendelian randomisation analysis in UK Biobank

BackgroundBrain iron deposition is common in dementia, but whether serum iron is a causal risk factor is unknown. We aimed to determine whether genetic predisposition to higher serum iron status...

Is Montreal Cognitive Assessment a valuable test for the differentiation of Alzheimer's disease, frontotemporal dementia, dementia with Lewy body, and vascular dementia?

This study examined the diagnostic value of the total MoCA score and its subscores in differentiating Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), and vascular dementia (VaD). A total of 241 patients (AD=110, FTD=90, DLB=28, and VaD=13) and 59 healthy persons, who were referred to a dementia clinic with memory impairment in Firoozgar Hospital, were included in this study. MoCA tests were performed in all patients and normal persons. By using the receiver operating characteristic (ROC) curve and measuring the area under the curve (AUC) for the total MoCA score in each group, AUC was 0.616, 0.681, 0.6117, and 0.583 for differentiating AD, FTD, DLB, and VaD patients, respectively. Among the groups, just the VaD group showed no significant usefulness in using the total MoCA score to differentiate it. To compare MoCA subscores, AD patients had higher scores in digit span, literal fluency, and abstraction but lower delayed recall scores compared with FTD patients. The total MoCA score and its subscores could not differentiate people with different types of dementia in the setting of screening.

Amide proton transfer could be a surrogate imaging marker for predicting vascular cognitive impairment

BackgroudEmerging evidence suggests an overlap in the underlying pathways contributing to both cerebral small vessel disease (CSVD) and the neurodegenerative disease. Studies investigating the progression of CSVD should incorporate markers that reflect neurodegenerative lesions. ObjectiveWe aim to investigate whether Amide proton transfer (APT) can serve as a potential marker for reflecting vascular cognitive impairment (VCI). MethodParticipants were categorized into one of three groups based on their Montreal Cognitive Assessment (MoCA) scores: normal control group (age,54.9 ± 7.9; male, 52.9%), mild cognitive impairment (MCI) group (age,55.7 ± 6.9; male, 42.6%), or vascular dementia (VaD) group (age,57.6 ± 5.5, male, 58.5%). One way analysis of variance was performed to compare the demographic and APT variables between groups. Multiple logistic regression analysis wwas constructed to examine the relationship between APT values and VCI grouping. A hierarchical linear regression model was employed to examine the associations between patients' demographic factors, imaging markers, APT values, and MoCA. ResultsThe APT values of frontal white matter, hippocampus, amygdala, and thalamus were significantly different among different groups (p < 0.05). The APT values of frontal white matter, amygdala, and thalamus indicate a significant positive effect on MCI grouping. the APT values of frontal white matter, amygdala, and thalamus indicate a significant positive effect on VaD grouping. The demographic data, CSVD imaging markers and APT values can account for 5.1%, 20.1% and 27.7% of the variation in MoCA, respectively. ConclusionAPT imaging can partially identifying and predicting the occurrence of VCI.

Second formant transitions for acoustic analysis to differentiate among dementia types

Recent evidence indicates that acoustic features associated with emotional prosody in speech may be an inexpensive, non-invasive method for differentiating among dementia types. In particular, frequency measures in the speech of people with dementia have been associated with listeners’ perception of emotional prosody. The purpose of this study was to determine if second formant (F2) transition information would enhance these differentiations. Prerecorded speech samples of Cookie Theft picture descriptions from 10 individuals with dementia of the Alzheimer’s type (DAT), 5 with vascular dementia (VaD), 9 with MCI, and 10 neurologically healthy controls (NHC) were obtained from the DementiaBank. Nine words that had initial obstruent consonants that occurred at least two times in each of the participant groups were selected for measurement. The F2 durations, extents, and slope were measured and analyzed. Across group comparisons revealed no pattern for F2 durations or extents. The fricatives had longer F2 durations than the plosives. Across word comparisons revealed significant differences across the consonant vowel combinations for all three measures. A group by word interaction occurred for the F2 slope with the VaD group exhibiting larger slopes than the other two groups.

Risk factors for vascular dementia

Background. An increase in the number of older people with cognitive disorders, including dementia, is expected.The aim. To study the risk factors for vascular dementia.Material and methods. 39 patients with vascular dementia (ICD-10 diagnosis code F01) were examined. The comparison group consisted of 167 people. According to the MMSE (Mini Mental State Examination) scale, moderate dementia was detected in 56.4 % of cases, severe – in 43.6 %; in the comparison group, 94 % had mild and 6 % – moderate cognitive impairment.Results. In the vascular dementia group, the following risk factors were registered significantly more often: ischemic heart disease – at the age of 70–79 years (57.1 %; p = 0.000) and in the group as a whole (56.4 %; p = 0.000); diabetes mellitus – at the age of 60–69 years (100 %; p = 0.005); arterial hypertension – at the age of 70–79 years (100 %; p = 0.000) and in the group as a whole (87.2 %; p = 0.000). In the comparison group, the frequency of body mass index over 25 was significantly higher at the age of 70–79 years (60 %; p = 0.000), 80 years and older (64.3 %; p = 0.037) and in the group as a whole (68.9 %; p = 0.000). Among people with moderate cognitive impairment, the following risk factors were significantly more common: coronary heart disease – at the age of 60–69 years (10 %; p = 0.001); diabetes mellitus – at the age of 70–79 years (40 %; p = 0.025) and in the group as a whole (50 %; p = 0.033), the frequency of body mass index over 25 – at the age of 80 years and older (70 %; p = 0.000) and in the group as a whole (100 %; p = 0.000).Conclusion. Risk factors for the development of cognitive disorders (coronary heart disease, hypertension, diabetes mellitus, overweight) are potentially reversible; their timely detection can reduce the development of cognitive disorders and dementia.

Early diagnostic value of intima-media thickness and D-dimer levels for vascular dementia.

To evaluate the diagnostic value of combination of D-dimer and Doppler Intima-Media Thickness (IMT) based on clinical data for vascular dementia (VaD). In this study, 100 cases of initial VaD were diagnosed by Zhenjiang Fourth People Hospital as VaD group, and 100 healthy were engaged as control group, medical history and test results were collected for evaluation. IMT and D-dimer were highly correlated with the onset of VaD. The sensitivity of combination diagnosis for early VaD: 90.2%, the specificity: 87.9%, the area under the curve (AUC) is 0.872, which were superior to IMT or D-dimer alone. D-dimer and IMT are significantly increased in the initial onset of cerebrovascular diseases, and combined detection of them is conducive to early diagnosis and evaluation of the disease. Given the limitations of D-dimer and IMT, combined detection is more conducive to early diagnosis and prognosis, and can be used as screening and routine examination items, even evaluate the severity of cognitive decline.

Dendrobium Nobile Polysaccharides Attenuates Ferroptosis and Improves Cognitive Function in Vascular Dementia Rats.

To investigate the neuroprotective effect and mechanism of Dendrobium nobile polysaccharide (DNP) on vascular dementia (VD) rats. VD model rats were prepared by permanent ligation of bilateral common carotid arteries. Cognitive function was tested by morris water maze test, mitochondrial morphology and ultrastructure of hippocampal synapses were tested by transmission electron microscopy, GSH, xCT, GPx4, and PSD-95 expressions were tested by western blot and PCR. The number of platform crossing was significantly increased, and the escape latency was significantly shorter in DNP group. The expressions of GSH, xCT and GPx4 in the hippocampus were up-regulated in DNP group. Moreover, the synapses of DNP group were relatively intact and synaptic vesicles increased, the length of synaptic active zone and PSD thickness were significantly increased, and PSD-95 protein expression was significantly up-regulated compared VD group. DNP may take a neuroprotective effect by inhibiting ferroptosis in VD.

Multi-approach comparative study of EEG patterns associated with the most common forms of dementia

Electroencephalography’s (EEG) sensitivity in discriminating dementia syndromes remains unclear. This study aimed to investigate EEG markers in patients with major cognitive disorders. The studied population included 4 groups of patients: Alzheimer's disease with associated vascular lesions, Alzheimer’s disease without vascular lesions (AD-V), Lewy body disease and vascular dementia (VaD); and completed by a control group composed by cognitively unimpaired patients. EEGs were analysed quantitatively using spectral analysis, functional connectivity and micro-states. By comparison to the controls, expected slowing and alterations of functional connectivity were detected in patients with dementia. Among these patients, an overall increase in power in the alpha band was observed in the VaD group, mainly when compared to the 2 AD groups, while the Alzheimer’s disease without vascular lesions group exhibited increased power in the beta-2 band and higher functional connectivity in the same frequency band. Micro-state analyses revealed differences in temporal dynamics for the VaD group.A number of EEG modifications reported as markers of some syndromes were found, but others were not reproduced.

Profiling inflammatory mechanisms, hyperphosphorylated tau of hippocampal tissue and spatial memory following vitamin D3 treatment in the mice model of vascular dementia

BackgroundThe aim of this study was to investigate the effect of vitamin D3 (VitD3) on inflammatory mechanisms, hyperphosphorylated tau (p-tau) in the hippocampus, and cognitive impairment of the mouse model of vascular dementia (VaD). MethodsIn this study, 32 male mice were randomly assigned to the control, VaD, VitD3 (300 IU/Kg/day), and VitD3 (500 IU/Kg/day) groups. VaD and VitD3 groups were gavaged daily for 4 weeks with a gastric needle. For biochemical assessments, blood samples and the hippocampus were isolated. IL-1β and TNF-α were analyzed by ELISA, and p-tau and other inflammatory molecules were measured by western blot. ResultsVitD3 supplements significantly (P < 0.05) decreased the level of inflammatory factors in the hippocampus and prevented apoptosis. However, regarding p-tau in hippocampal tissue, this decrease was not statistically significant (P > 0.05). The results of behavioral assessments showed that VitD3 significantly improved the spatial memory of treated mice. ConclusionThese results suggest that the neuroprotective effects of VitD3 are mainly associated with their anti-inflammatory effects.

Integrated transcriptome and metabolome analysis to investigate the mechanism of intranasal insulin treatment in a rat model of vascular dementia.

Introduction: Insulin has an effect on neurodegenerative diseases. However, the role and mechanism of insulin in vascular dementia (VD) and its underlying mechanism are unknown. In this study, we aimed to investigate the effects and mechanism of insulin on VD. Methods: Experimental rats were randomly assigned to control (CK), Sham, VD, and insulin (INS) + VD groups. Insulin was administered by intranasal spray. Cognitive function was evaluated using the Morris's water maze. Nissl's staining and immunohistochemical staining were used to assess morphological alterations. Apoptosis was evaluated using TUNEL-staining. Transcriptome and metabolome analyses were performed to identify differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs), respectively. Results: Insulin significantly improved cognitive and memory functions in VD model rats (p < 0.05). Compared with the VD group, the insulin + VD group exhibited significantly reduced the number of Nissl's bodies numbers, apoptosis level, GFAP-positive cell numbers, apoptosis rates, and p-tau and tau levels in the hippocampal CA1 region (p < 0.05). Transcriptomic analysis found 1,257 and 938 DEGs in the VD vs. CK and insulin + VD vs. VD comparisons, respectively. The DEGs were mainly enriched in calcium signaling, cAMP signaling, axon guidance, and glutamatergic synapse signaling pathways. In addition, metabolomic analysis identified 1 and 14 DEMs between groups in negative and positive modes, respectively. KEGG pathway analysis indicated that DEGs and DEMs were mostly enriched in metabolic pathway. Conclusion: Insulin could effectively improve cognitive function in VD model rats by downregulating tau and p-tau expression, inhibiting astrocyte inflammation and neuron apoptosis, and regulating genes involved in calcium signaling, cAMP signaling, axon guidance, and glutamatergic synapse pathways, as well as metabolites involved in metabolic pathway.

Diffusion Tensor Imaging as a Tool to Evaluate the Cognitive Function of Patients With Vascular Dementia: A Meta-Analysis.

Vascular dementia (VaD) is the most common type of dementia secondary to Alzheimer's disease. The pathologic mechanism of VaD is complex, and VaD still lacks a more objective diagnosis and evaluation method. Diffusion tensor imaging (DTI) can better detect the organizational structure and functional characteristics compared with any other diagnosis methods. Therefore, DTI has broad application in evaluating the severity and prognosis of VaD. This study aimed to assess the value of DTI in evaluating the cognitive function of patients with VaD. Authors searched Pubmed, Embase, and Cochrane Library, using the search terms, such as "diffusion tensor imaging," "DTI," "Vascular Dementia," "Arteriosclerotic Dementia," "Cognition," and "Cognitive." A voxel-based meta-analysis combined with quality statistics was performed, using the anisotropic effect-size version of the signed differential mapping method. A total of 8 case-control studies were included in this meta-analysis. The sample size of patients ranged from 35 to 60, including 166 patients in the VaD group and 177 healthy individuals. The DTI imaging of the brain tissue of VaD patients was significantly different from that of healthy individuals. DTI imaging of the brain tissue of VaD patients was clearly different from that of healthy controls. Therefore it may be feasible to use DTI imaging as a diagnostic method for VaD.