Risk Factor For Vascular Dementia Research Articles

Hypercholesterolemia and the Increased Risk of Vascular Dementia: a Cholesterol Perspective.

Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer's disease.Hypercholesterolemia may increase the risk of dementia, but the association between cholesterol and cognitive function is very complex. From the perspective of peripheral and brain cholesterol, we review the relationship between hypercholesterolemia and increased risk of VaD and how the use of lipid-lowering therapies affects cognition. Epidemiologic studies show since 1980, non-HDL-C levels of individuals has increased rapidly in Asian countries.The study has suggested that vascular risk factors increase the risk of VaD, such as disordered lipid metabolism. Dyslipidemia has been found to interact with chronic cerebral hypoperfusion to promote inflammation resulting in cognitive dysfunction in the brain.Hypercholesterolemia may be a risk factor for VaD. Inflammation could potentially serve as a link between hypercholesterolemia and VaD. Additionally, the potential impact of lipid-lowering therapy on cognitive function is also worth considering. Finding strategies to prevent and treat VaD is critical given the aging of the population to lessen the load on society. Currently, controlling underlying vascular risk factors is considered one of the most effective methods of preventing VaD. Understanding the relationship between abnormal cholesterol levels and VaD, as well as discovering potential serum biomarkers, is important for the early prevention and treatment of VaD.

Exploring the common mechanism of vascular dementia and inflammatory bowel disease: a bioinformatics-based study.

Emerging evidence has shown that gut diseases can regulate the development and function of the immune, metabolic, and nervous systems through dynamic bidirectional communication on the brain-gut axis. However, the specific mechanism of intestinal diseases and vascular dementia (VD) remains unclear. We designed this study especially, to further clarify the connection between VD and inflammatory bowel disease (IBD) from bioinformatics analyses. We downloaded Gene expression profiles for VD (GSE122063) and IBD (GSE47908, GSE179285) from the Gene Expression Omnibus (GEO) database. Then individual Gene Set Enrichment Analysis (GSEA) was used to confirm the connection between the two diseases respectively. The common differentially expressed genes (coDEGs) were identified, and the STRING database together with Cytoscape software were used to construct protein-protein interaction (PPI) network and core functional modules. We identified the hub genes by using the Cytohubba plugin. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to identify pathways of coDEGs and hub genes. Subsequently, receiver operating characteristic (ROC) analysis was used to identify the diagnostic ability of these hub genes, and a training dataset was used to verify the expression levels of the hub genes. An alternative single-sample gene set enrichment (ssGSEA) algorithm was used to analyze immune cell infiltration between coDEGs and immune cells. Finally, the correlation between hub genes and immune cells was analyzed. We screened 167 coDEGs. The main articles of coDEGs enrichment analysis focused on immune function. 8 shared hub genes were identified, including PTPRC, ITGB2, CYBB, IL1B, TLR2, CASP1, IL10RA, and BTK. The functional categories of hub genes enrichment analysis were mainly involved in the regulation of immune function and neuroinflammatory response. Compared to the healthy controls, abnormal infiltration of immune cells was found in VD and IBD. We also found the correlation between 8 shared hub genes and immune cells. This study suggests that IBD may be a new risk factor for VD. The 8 hub genes may predict the IBD complicated with VD. Immune-related coDEGS may be related to their association, which requires further research to prove.

Vascular, Imaging and Cognition Association of China (VICA) Study: Rationale and Design

AbstractBackgroundChina has the highest number of patients with dementia in the world, and about 15‐30% of these cases are caused by vascular disease. Currently, the pathophysiological mechanism that cause vascular cognitive impairment (VCI) remain insufficiently understood. Therefore, early diagnosis and prognostic indicators of VCI are critically important for managing its onset and development To this end, several Chinese institutions have joined forces to establish “Vascular, Imaging and Cognition Association of China” (VICA) (Figure 1). The objective of VICA is to identify new targets for intervention and prompting intelligent graded and stratified treatment.MethodVICA is the first large‐scale multi‐center VCI consortium in China. It consists of seven advanced centers and over two hundred primary hospitals across the country. Included VICA are three different populations at risk for VCI: (a) high vascular risk factors for dementia, (b) cerebral small vessel disease, and (c) acute ischemic stroke or transient ischemic attacks (TIA).ResultAll individuals will be enrolled and monitored for at least 1 year using serial neuropsychological assessment, neuroimaging and collection of multi‐omics data from biospecimens (e.g., blood, urine, feces). In addition, a small sample of patients will undergo PET scans to determine whether neurodegenerative pathology (such as amyloid or tau accumulation) contributes to the course of vascular dementia. The enrollment procedure of patients with stroke or TIA is shown in Figure 2.ConclusionThe overall scientific aim of VICA is to guide early clinical diagnosis and early intervention of VCI based on the integration of multiple vascular risk factors, neuroimaging features and biomarkers. VICA represents a unique scientific resource that will help better understand the dynamics of cognitive change in different populations and identify new potential therapeutic targets for this condition.

Determining Vascular Risk Factors for Dementia and Dementia Risk Prediction Across Mid- to Later Life: The Framingham Heart Study.

Determining Vascular Risk Factors for Dementia and Dementia Risk Prediction Across Mid- to Later Life: The Framingham Heart Study.

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.

Speech biomarkers of risk factors for vascular dementia in people with mild cognitive impairment.

In this study we intend to use speech analysis to analyze the cognitive impairments caused by pathologies of vascular origin such as diabetes, hypertension, hypercholesterolemia and heart disease, predictors of the development of vascular dementia. In this study, 40 participants with mild cognitive impairment were asked to read while being recorded and they were inquired about their history of the aforementioned conditions. Their speech was then analyzed. We found that some speech parameters of frequencies and syllabic rhythm vary due to these pathologies. In addition, we conducted a discriminant analysis in which we found that diabetes and hypertension can be predicted with an accuracy over 95% with few speech parameters, and hypercholesterolemia and heart disease with an accuracy over 80%. The predictor parameters found are heterogeneous, including voice quality, amplitude, frequency, and rhythm parameters. This result may lead to investigate why such important qualitative changes occur in the voice of older adults with these pathologies. Rather than trying to find a diagnostic procedure already existing in classical medicine, we expect this finding to contribute to explore the causes and concomitant pathologies of these diseases. We discuss the implications of behavioral traits, such as speech, as digital biomarkers.

MicroRNA-195 rescues the impaired MS-dCA1 neural circuit and spatial memory in rats with chronic cerebral hypoperfusion

Chronic cerebral hypoperfusion (CCH) is a common risk factor for vascular dementia and Alzheimer’s disease (AD). The previous studies have shown that CCH-induced multiple AD-like pathological changes in the hippocampus and cortex through downregulating the microRNA-195 (miR-195) expression. However, whether and how miR-195 participates in the dysfunction of the medial septum (MS)-dorsal hippocampal CA1 (dCA1) neural circuit following CCH is still obscure. In the present study, we found that miR-195 was downregulated in the MS region of CCH rats. Moreover, using electrophysiological recording and immunofluorescence staining technique, we found that the knockdown of miR-195 through the injection of lenti- AMO-195 into the MS region led to a pathological change that mimicked the damage to the MS-dCA1 neural circuit in CCH rats, including the decreased input-output (I/O) curve, increased paired-pulse ratio (PPR), decreased numbers of ChAT+ and PV+ neurons in MS, and diminished theta rhythm in the hippocampus. More importantly, exogenously supplemented miR-195 into the MS region rescued the damaged neural circuit in MS-dCA1 of CCH rats by injecting lenti-pre-miR-195. Gain-of-function of miR-195 in the MS region significantly improved the cognitive dysfunction in CCH rats assessed by the Morris water maze test. In conclusion, knockdown of miR-195 in the MS region can impair MS-dCA1 neural circuit function, while upregulation of miR- 195 can rescue the impaired function of MS-dCA1 neural circuit and spatial memory ability in CCH rats. This provides a valuable reference for future anti-dementia therapy involving miR-195.

Assessing the role of vascular risk factors in dementia: Mendelian randomization meta-analysis and comparison with observational estimates

Background: Although observational studies demonstrate that higher levels of vascular risk factors are associated with an increased risk of dementia, these associations might be explained by confounding or other biases. Mendelian randomization (MR) uses genetic instruments to test causal relationships in observational data. We sought to determine if genetically predicted modifiable risk factors (type 2 diabetes mellitus, low density lipoprotein cholesterol, high density lipoprotein cholesterol, total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, body mass index, and circulating glucose) are associated with dementia by meta-analysing published MR studies. Secondary objectives were to identify heterogeneity in effect estimates across primary MR studies and to compare meta-analysis results with observational studies. Methods: MR studies were identified by systematic search of Web of Science, OVID and Scopus. We selected primary MR studies investigating the modifiable risk factors of interest. Only one study from each cohort per risk factor was included. A quality assessment tool was developed to primarily assess the three assumptions of MR for each MR study. Data were extracted on study characteristics, exposure and outcome, effect estimates per unit increase, and measures of variation. Effect estimates were pooled to generate an overall estimate, I2 and Cochrane Q values using fixed-effect model. Results: We screened 5211 studies and included 12 primary MR studies after applying inclusion and exclusion criteria. Higher genetically predicted body mass index was associated with a higher odds of dementia (OR 1.03 [1.01, 1.05] per 5 kg/m2 increase, one study, p=0.00285). Fewer hypothesized vascular risk factors were supported by estimates from MR studies than estimates from meta-analyses of observational studies. Conclusion: Genetically predicted body mass index was associated with an increase in risk of dementia.

Determining Vascular Risk Factors for Dementia and Dementia Risk Prediction Across Mid- to Later Life: The Framingham Heart Study.

The association between vascular risk factors and dementia varies with age, making generalizability of dementia risk prediction rules to individuals of different ages challenging. We determined the most important vascular risk factors for inclusion in age-specific dementia risk scores. Framingham Heart Study Original and Offspring cohort participants with available data on the Framingham Stroke Risk Profile (FSRP) at midlife (age 55; n = 4,899, 57% women), late life (ages 65 or 70), or later life (ages 75 or 80 [n = 2,386, 62% women]) were followed for 10-year incident dementia risk from ages 65, 70, 75, and 80. Age- and sex-adjusted midlife risk factors associated with 10-year risk of dementia from age 65 included FSRP (hazard ratio [HR] 1.16, 95% CI 1.06-1.26, per 1 SD increment in log-transformed score), diabetes mellitus (DM; HR 4.31, 95% CI 1.97-9.43), and systolic blood pressure (SBP; HR 1.12, 95% CI 1.02-1.24, per 10 mm Hg increment). Late-life risk factors associated with 10-year incident dementia from ages 65 or 70 included FSRP (age 65 only: HR 1.06, 95% CI 1.02-1.10), antihypertensive use (age 65 reported: HR 1.66, 95% CI 1.12-2.46), DM (age 65 reported: HR 1.96, 95% CI 1.09-3.52), atrial fibrillation (age 65 reported: HR 2.30, 95% CI 1.00-5.27), nonstroke cardiovascular disease (nsCVD; age 65 reported: HR 1.95, 95% CI 1.24-3.07), and stroke (age 70 only: HR 3.61, 95% CI 2.21-5.92). Later-life risk factors associated with 10-year incident dementia from ages 75 or 80 included antihypertensive use (age 80 only: HR 0.74, 95% CI 0.62-0.89), DM (age 80 reported: HR 1.40, 95% CI 1.04-1.89), atrial fibrillation (age 80 reported: HR 1.43, 95% CI 1.07-1.92), and stroke (age 80 reported: HR 1.63, 95% CI 1.13-2.35). In stepwise models, SBP and DM at age 55, nsCVD at age 65, DM and stroke at ages 70 and 75, and DM, stroke, and use of antihypertensives (protective) at age 80 were the most important vascular risk factors for dementia. Our findings support the use of age-specific dementia risk scores, which should prioritize including, at age 55, SBP and DM; at age 65, nsCVD; at ages 70 and 75, DM and stroke; and at age 80, DM, stroke, and antihypertensive use.

Individual prediction and classification of cognitive impairment in patients with white matter lesions based on gray matter volume.

BackgroundVascular risk factors like white matter lesions (WMLs) are increasingly recognized as risk factors for vascular dementia (VaD) and can predict Alzheimer’s disease (AD) at least a decade before the clinical stage of the disease. This study aimed to predict cognitive decline and use machine learning techniques to classify older individuals (aged 50 years or older) with WMLs as having vascular mild cognitive impairment (VaMCI), VaD, or in good cognitive health (CH).MethodsA total of 79 individuals with WMLs were selected for this study and categorized into the following 3 groups: CH (n=25), VaMCI (n=33), and VaD (n=21). Data from the entire cohort was then divided into a training dataset (n=56) and testing dataset (n=23). The data were extracted from gray matter (GM) segmentations using voxel-based morphometry (VBM). A relevance vector regression (RVR) approach was used to test the relationship between the structural brain images and clinical scores. To predict the individual-level subtypes, we applied 2 different machine learning-based classifiers: support vector machine (SVM) and Gaussian process classification (GPC). All predictive models were trained on the training dataset and then validated on the testing dataset of age-matched participants.ResultsMulti-domain cognitive performance could be predicted based on the pattern of GM atrophy in older people with WMLs using a RVR approach. The classification of VaD versus CH (cross-validation accuracy =93.94%, test set accuracy =76.92%) and VaMCI versus CH (cross-validation accuracy =95.24%, test set accuracy =87.50%) could be successfully achieved using both SVM and GPC. However, SVM (cross-validation accuracy =67.57%, test set accuracy =70.59%) performed better than GPC in the classification of VaD versus VaMCI.ConclusionsBased on the patterns of gray matter and RVR-based model could achieve prediction of cognitive test scores, and SVM and GPC could classify the severity of cognitive impairment in older people with WMLs.

Losartan enhances cognitive and structural neuroplasticity impairments in spontaneously hypertensive rats

Hypertension is a risk factor for vascular dementia, which is the second most prevalent type of dementia, just behind Alzheimer’s disease. This highlights the brain vulnerability due to hypertension, which may increase with aging. Thus, studying how hypertension affects neural cells and behavior, as well as the effects of antihypertensives on these alterations, it’s important to understand the hypertension consequences in the brain. The spontaneously hypertensive rat (SHR) has been useful for the study of hypertension alterations in diverse organs, including the brain. Thus, we studied the losartan effects on cognitive and structural neuroplasticity impairments in SHR of 10 months of age. In the first instance, we evaluated the losartan effects on exploratory behavior and novel object recognition test (NORT) in the SHR. Then, we assessed the density and morphology of dendritic spines of pyramidal neurons from the prefrontal cortex (PFC) layers 3 and 5, and CA1 of the dorsal Hp (dHp). Our results indicate that in SHR, losartan treatment (2 months, 15 mg/Kg/day) reduces high blood pressure to age-matched vehicle-treated Wistar-Kyoto (WKY) rat levels. Moreover, losartan improved long-term memory in SHR compared with age-matched vehicle-treated WKY rats, without affecting the locomotor and anxiety behaviors. The behavioral improvement of the SHR can be associated with the increase in the number of dendritic spines and the mushroom spine population in the PFC and the dHp. In conclusion, losartan enhances cognitive impairments by controlling the high blood pressure and improving neuroplasticity in animals with chronic hypertension.

Ischemia‐triggered, immune‐mediated neurodegeneration as a component of VCID

AbstractBackgroundPost‐stroke cognitive decline is an important component of vascular dementia. Ischemia and vascular disease is present in the brains of the majority of both Alzheimer’s Disease and VCID cases, and brain ischemia alone, in the form of a clinical stroke, doubles the risk of later cognitive impairment independently of known vascular dementia risk factors. In stroke survivors one of the most distressing complications is post‐stroke cognitive decline, which occurs in up to a third of individuals within five years and impacts significantly on quality of life.MethodsTo disentangle the effects of ischemia from other vascular mechanisms of dementia, we utilize mouse models of post‐stroke cognitive decline in adult and aged mice, mouse behavior, immunohistochemistry, and gene expression. In addition, we utilize prospective longitudinal cohort studies in human stroke survivors to examine how immune phenotyping of peripheral blood predicts cognitive decline at one year and chronically.ResultsWe found that normal wildtype mice develop delayed cognitive decline after stroke that is associated with a chronic neuroimmune response characterized by B and T lymphocyte infiltration of the stroke. Both genetic and drug studies demonstrate that B lymphocytes are necessary for post‐stroke cognitive decline. In humans with stroke and dementia, we find similar B and T cell infiltration. In a prospective longitudinal cohort of stroke survivors tested with a comprehensive cognitive test battery we see a high rate of cognitive impairment in at least one cognitive domain among the participants. In keeping with an autoimmune‐like mechanism, humans with immune alterations in the acute phase after stroke are more likely to have cognitive decline after stroke.ConclusionsTaken together we have demonstrated that normal mice exhibit ischemia‐triggered immune‐mediated neurodegeneration after stroke. Human studies demonstrate similar mechanisms, however more work remains to be done to identify immune mechanisms and biomarkers that predict cognitive decline in living humans after stroke. It will then be important to determine how much these post‐ischemia maladaptive immune responses contribute to VCID.

Editors' Note: Kidney Function, Kidney Function Decline, and the Risk of Dementia in Older Adults

Dr. Xu et al. analyzed the association of kidney function with the risk of dementia in a registry of 329,822 residents of Stockholm (2006–2011), additionally assessing the association with decline in kidney function in 205,622 residents who had repeated measurements in the first year of observation. Over a median follow-up of 5 years, they found that both lower kidney function and steeper decline in kidney function were associated with the development of dementia. In response, Dr. Fischereder highlighted uncertainties about the causal association of kidney function with cognitive function and postulates that the association likely reflects common causes of renal impairment and cognitive decline such as microvascular disease. Dr. Fischereder noted potential implications of a true causal association for patients with iatrogenically decreased kidney function, such as living kidney donors. Although the authors adjusted their analyses for key comorbidities, Dr. Fischereder noted the increasing risk of dementia observed even in people with high estimated glomerular filtration rate (eGFR) in the cohort after this adjustment and suggested a subgroup analysis specifically in patients who are free of diabetes mellitus, hypertension, or tobacco use. Responding to these comments, the authors agree that causation cannot be inferred from their data but note other studies indicating an association between cognitive impairment and renal dysfunction. Regarding the underlying mechanisms, they point to experimental evidence that various uremia-induced processes may lead to dementia. They agree that chronic kidney disease may be a risk mediator for other vascular risk factors for dementia but also note that they found similar associations in people with and without diabetes or hypertension. They hypothesize that some people with especially high eGFR in the cohort may have had glomerular hyperfiltration or low muscle mass but are wary of conclusions based on dementia risk in that subgroup. They also caution against extrapolating their findings to kidney donors, noting that 10-year follow-up studies show a consistent increase in GFR for such individuals during the first few years postdonation, followed by a decline at a slower rate than controls. In summary, this exchange highlights the uncertain pathophysiologic mechanisms of the observed association between renal function and cognitive decline. At present, one might reasonably conclude that patients with renal impairment merit screening for cognitive disorders. Dr. Xu et al. analyzed the association of kidney function with the risk of dementia in a registry of 329,822 residents of Stockholm (2006–2011), additionally assessing the association with decline in kidney function in 205,622 residents who had repeated measurements in the first year of observation. Over a median follow-up of 5 years, they found that both lower kidney function and steeper decline in kidney function were associated with the development of dementia. In response, Dr. Fischereder highlighted uncertainties about the causal association of kidney function with cognitive function and postulates that the association likely reflects common causes of renal impairment and cognitive decline such as microvascular disease. Dr. Fischereder noted potential implications of a true causal association for patients with iatrogenically decreased kidney function, such as living kidney donors. Although the authors adjusted their analyses for key comorbidities, Dr. Fischereder noted the increasing risk of dementia observed even in people with high estimated glomerular filtration rate (eGFR) in the cohort after this adjustment and suggested a subgroup analysis specifically in patients who are free of diabetes mellitus, hypertension, or tobacco use. Responding to these comments, the authors agree that causation cannot be inferred from their data but note other studies indicating an association between cognitive impairment and renal dysfunction. Regarding the underlying mechanisms, they point to experimental evidence that various uremia-induced processes may lead to dementia. They agree that chronic kidney disease may be a risk mediator for other vascular risk factors for dementia but also note that they found similar associations in people with and without diabetes or hypertension. They hypothesize that some people with especially high eGFR in the cohort may have had glomerular hyperfiltration or low muscle mass but are wary of conclusions based on dementia risk in that subgroup. They also caution against extrapolating their findings to kidney donors, noting that 10-year follow-up studies show a consistent increase in GFR for such individuals during the first few years postdonation, followed by a decline at a slower rate than controls. In summary, this exchange highlights the uncertain pathophysiologic mechanisms of the observed association between renal function and cognitive decline. At present, one might reasonably conclude that patients with renal impairment merit screening for cognitive disorders.

Are tomorrow’s doctors prepared to prevent dementia? A cross-sectional study of Tasmanian medical students’ knowledge of dementia risk factors

Tomorrow’s doctors are unprepared to prevent dementia. This cross-sectional study invited medical students enrolled in the University of Tasmania 5-year medical degree (MBBS) to participate in an online questionnaire during 2019. This study measured students’ recall of risk factors, prompted and unprompted, for dementia and cardiovascular disease (CVD), and Dementia Knowledge Assessment Scale (DKAS) score. Data were collected via an online survey comprising the DKAS, and risk factor questions adapted from the Alzheimer’s Research UK National Monitor Survey, with questions on CVD risk factors added for comparison. Medical students (n = 82) proffered fewer unprompted risk factors for dementia than for CVD and were less proficient at recognizing dementia risk factors from a prompted list. Knowledge of vascular risk factors for dementia was particularly limited. Their broader dementia knowledge was generally adequate and DKAS scores were at the level of a qualified doctor by final year. Whilst medical students’ general knowledge of dementia was satisfactory, their knowledge of modifiable risk factors of dementia was limited. If replicated elsewhere, this raises concerns about whether the future medical workforce is equipped to take a necessary lead role in managing dementia risk reduction. As dementia incidence rises worldwide, and 40% cases are attributable to modifiable risk factors, educational programs may need to urgently address these deficiencies.

ShenmaYizhi Decoction Improves the Mitochondrial Structure in the Brain and Ameliorates Cognitive Impairment in VCI Rats via the AMPK/UCP2 Signaling Pathway.

BackgroundShenmaYizhi decoction (SMYZD) is an effective prescription of traditional Chinese medicine used to treat vascular dementia (VD). Modern research methods have identified its active ingredients clearly as gastrodin, ferulic acid, ginsenosides, and β-sitosterol. Chronic cerebral hypoperfusion is a driving factor or risk factor for VD, which leads to the disturbance of mitochondrial structure and function.PurposeTo observe whether SMYZD improves cognitive impairment by improving mitochondrial structure and function.MethodsForty adult rats with vascular cognitive impairment (VCI) caused by the bilateral ligation of common carotid arteries were divided into four groups randomly, including the model group, donepezil group, and low-dose and high-dose SMYZD groups, with 10 rats in each group. Additionally, a sham group was established with 10 rats as the control group. The treatment groups were administered donepezil and two different dosages of SMYZD. The donepezil group was administered 0.45 mg/kg/d donepezil, and the SMYZ-L group was administered 2.97 g/kg/d SMYZ, which were equivalent to the clinical dosage. The SMYZ-H group was administered 11.88 g/kg/d SMYZ, which is 4 times higher than the clinically equivalent dosage. A sham-operated group was used as the control group and administered an equal volume of distilled water. The rats were treated by gavage for 8 consecutive weeks. Morris water maze (MWM) test was performed to evaluate the learning and memory ability. The mitochondria of brain tissue were extracted from brain for further test. Mitochondrial morphology and the signal path of AMPK/PPARα/PGC-1α/UCP2 in mitochondria were detected.ResultsWith the SMYZD intervention, behavioral performance of rats and pathological changes of mitochondria of brain tissue were significantly improved. In the serum, SOD, GSH-Px, and GSH activities were increased, and the MDA content was decreased. Moreover, the AMPK, PPARα, PGC-1α, UCP2, and ATP5A mRNA and protein expression levels were also reversed by SMYZD.ConclusionSMYZD may provide a potential therapeutic strategy via activating the AMPK/PPARα/PGC-1α/UCP2 signal pathway to improve mitochondrial structure and energy metabolism thereby alleviate vascular cognitive impairment.

Multiomics Investigation of Hypertension and White Matter Hyperintensity as a Source of Vascular Dementia or a Comorbidity to Alzheimer's Disease.

Age-related comorbidity is common and significantly increases the burden for the healthcare of the elderly. Alzheimer's disease (AD) and hypertension are the two most prevalent age-related conditions and are highly comorbid. While hypertension is a risk factor for vascular dementia (VD), hypertension with AD (ADHyp+) is often characterized as probable vascular dementia. In the absence of imaging and other diagnostic tests, differentiating the two pathological states is difficult. Our goals are to (1) identify differences in CSF-based vascular dementia profiles, if any, between individuals who have AD only (ADHyp-), and individuals with ADHyp+ using CSF levels of amyloid β, tau and p-tau, and (2) compare genome-wide DNA profiles of ADHyp- and ADHyp+ with an unaffected control population. Genotype and clinical data were used to compare healthy controls to AD Hyp- vs. AD Hyp+. We compared the CSF biomarkers followed by evaluating genome wide profiles in three groups, and mapped SNPs to genes based on position and lowest p-value. The significant genes were examined for co-expression and known disease networks. We found no differences between Aβ, tau and p-tau levels between ADHyp- and ADHyp+. We found TOMM40 to be associated with ADHyp- as expected but not with ADHyp+. Interestingly, SLC9A3R2 polymorphism was associated with ADHyp+, and significant gene expression changes were observed for neighboring genes. Through this exploratory study using a novel cohort stratification design, we highlight the genetic differences in clinically similar phenotypes, indicating the utility of genetic profiling in aiding differential diagnosis of ADHyp+ and VD.

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.

Preservation of spatial memory and neuroprotection by the fatty acid amide hydrolase inhibitor URB597 in a rat model of vascular dementia.

BackgroundChronic cerebral hypoperfusion (CCH) is a major risk factor for vascular dementia (VaD). There are currently no broadly effective prevention or treatment strategies for VaD, but recent studies have reported promising results following vascular bypass surgery and pharmacomodulation of the brain endocannabinoid system (ECS). In this study, early effects of encephalomyosynangiosis (EMS) bypass surgery and augmented endocannabinoid signaling on CCH-induced cognitive dysfunction and neuronal damage were investigated.MethodsAn animal model of VaD was established by bilateral common carotid artery occlusion (BCCAO). Cannabinoid signaling was upregulated by treatment with the fatty acid amide hydrolase inhibitor URB597 (URB). Spatial learning and memory, cerebral blood flow (CBF), revascularization, brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling, and apoptosis were compared among Sham, BCCAO, BCCAO + EMS, BCCAO + URB, and BCCAO + URB + EMS groups. Spatial learning and memory were evaluated using the Morris water maze (MWM). The CBF in cortex and hippocampus was evaluated by 3-dimensional arterial spin labeling. The neovascularization was visualized by CD34 immunofluorescence staining, and BDNF-TrkB signaling protein expression levels were assessed by Western blotting.ResultsTreatment with URB597 but not EMS alone reversed the spatial learning and memory deficits induced by BCCAO. Neovascularization was enhanced after EMS surgery but not by URB597. Alternatively, there were no significant differences in CBF among treatment groups. Expression levels of BDNF and TrkB were significantly reduced by CCH compared to Sham treatment, and downregulation of both proteins was reversed by URB597 treatment but not EMS. BCCAO enhanced neuronal apoptosis, which was also reversed by URB597.ConclusionsAugmentation of endogenous cannabinoid signaling but not EMS protects against CCH-induced neurodegeneration and preserves spatial learning and memory, possibly by activating BDNF-TrkB signaling.

Association Between Homocysteine and Vitamin Levels in Demented Patients.

Although it is known that the nutritional status among elderly persons and, in particular, patients with dementia, is compromised, malnutrition that results in insufficient uptake of several vitamins is often not diagnosed. An elevated homocysteine level is a known strong risk factor for vascular dementia (VaD) and Alzheimer's disease (AD). Several B vitamins are involved in the metabolism of homocysteine. Therefore, we investigated the serum levels of vitamin B1, vitamin B6, folate, and vitamin B12 in 97 patients with mild cognitive impairment (MCI) or different forms of dementia and 54 elderly control persons without dementia. Compared to aged non-demented people, vitamins B1, B6, B12, and folate were decreased in serum of patients with AD, and patients with Lewy body dementia had reduced vitamin B12 level. Vitamin B6 was diminished in VaD. Patients with frontotemporal dementia showed no alterations in vitamin levels. Age was identified as an important factor contributing to the concentrations of vitamin B1 and B6 in serum, but not vitamin B12 and folate. Increased levels of total homocysteine were detected especially in MCI and AD. Homocysteine correlated negatively with levels of vitamins B6, B12, and folate and positively with Q Albumin. Our data suggest that despite increased homocysteine already present in MCI, vitamin levels are decreased only in dementia. We propose to determine the vitamin levels in patients with cognitive decline, but also elderly people in general, and recommend supplementing these nutrients if needed.

The Association Between Hypertension and Cognitive Impairment, and the Role of Antihypertensive Medications: A Literature Review.

Vascular dementia (VD) is one of the leading causes of dementia, and hypertension is a known risk factor for VD. Hypertension treatment guidelines have previously discussed an optimal blood pressure goal to prevent further cardiovascular complications with long-term management. The treatment of hypertension can prevent stroke, kidney failure, and perhaps prevent cognitive decline as well. We reviewed studies that demonstrated an association between hypertension and cognitive impairment (CI). The role of antihypertensive medications (AHM) in preventing CI was also investigated. This topic is worth exploring as dementia has high healthcare costs and will become prominent as the population in the United States ages. We used the medical subject heading (MeSH) search strategy on Pubmed and reviewed 22 articles. The studies showed that there might be a link between hypertension, AHM, and CI. The studies did not suggest a superiority of any specific AHM class to prevent CI. Further research on optimal hypertension treatment goals to prevent cognitive impairment and dementia is recommended.