Risk Of Vascular Dementia Research Articles

Abstract 4136600: Hypertensive disorders of pregnancy and the risk of Dementia, Alzheimer’s disease, and Vascular Dementia. A Systematic review and Meta-analysis of 25,03,538 women participants.

Background: Hypertensive disorders of pregnancy (HDP) are associated with maternal adverse cardiovascular outcomes. However, their association with maternal Dementia and Alzheimer’s disease is not well established with limited and conflicting results to date. Objective: We sought to evaluate the association between HDP and risk of incidence of Dementia, and Alzheimer’s disease. Methods: We performed a systematic review and meta-analysis of available literature that enrolled women with HDP and women without HDP groups. PubMed, Embase and ClinicalTrials.gov were systematically searched from inspection till May 2024 without any language restrictions. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were pooled using a random-effect model. Results: A total of 8 studies with 2503538 patients (1,51,905 in women with HDP and 23,51,633 in the women without HDP group) were included. Pooled analysis shows that HDP women were having 37% higher risk of dementia (aHR, 1.37(95%CI: 1.27-1.46), P<0.001, I2=0%) when compared with women without HDP. Further pooled analysis showed that women with HDP were having 28% higher risk of Alzheimer’s disease (aHR, 1.28(95%CI: 1.56), P<0.001, I2=53.98%), and 2-fold higher risk of vascular dementia (aHR, 2.49(95%CI: 1.29-3.68), P<0.001, I2=71.51%) when compared with women without HDP. Conclusion: Women with HDP were at higher risk of developing Dementia, and Alzheimer's disease in future.

Hyperthyroidism, hypothyroidism, thyroid stimulating hormone, and dementia risk: results from the NHANES 2011-2012 and Mendelian randomization analysis.

As the world ages, dementia places a heavy burden on society and the economy, but current methods of diagnosing dementia are still limited and there are no better therapies that target the causes of dementia. The purpose of this work is to explore the relationship between thyroid disease, thyroid stimulating hormone (TSH) concentrations, free tetraiodothyronine (FT4) concentrations and cognitive function. This study utilized cognitive function and thyroid data from the 2011-2012 National Health and Nutrition Examination Survey (NHANES) to assess the relationship between different groups of TSH and FT4 concentrations and cognitive function using weighted logistic regression and restricted cubic spline (RCS), and then used two-sample Mendelian Randomization (MR) to assess the causal relationship between hyperthyroidism, hypothyroidism, TSH and FT4 concentrations with dementia. Our analysis of the 2011-2012 NHANES data showed that the individuals with low TSH concentrations had higher Alzheimer's Disease Word List Registry Consortium1 (CERAD1) and CERAD.delay.recall scores than individuals with high TSH concentrations, and individuals with low FT4 concentrations had higher CERAD3 and Animal Fluency Test scores than individuals with high FT4 concentrations. Our results also showed a non-linear relationship between serum TSH and FT4 concentrations and the Animal Fluency Test. The TSH concentrations within the range of 1.703 to 3.145 mIU/L exhibit a positive correlation with Animal Fluency Test, whereas concentrations outside this range are negatively correlated with Animal Fluency Test. The FT4 concentrations exhibited a positive correlation with Animal Fluency Test to the left of the FT4 concentrations inflection point (0.849 ng/L), whereas to the right of this inflection point, correlation was negative. MR analysis results further indicate that genetic predisposition to hyperthyroidism may be associated with a reduced risk of dementia and vascular dementia(VaD). Conversely, genetic predisposition to hypothyroidism appears to be linked with an increased risk of dementia and VaD. Additionally, genetic predisposition to elevated TSH concentrations may be correlated with a heightened risk of risk of Alzheimer's disease (AD). This study provides evidence of a nonlinear relationship between TSH and FT4 concentrations and cognitive function, with hyperthyroidism decreasing the risk of dementia and VaD, hypothyroidism increasing the risk of dementia and VaD, and elevated serum TSH concentrations increasing the risk of AD. Furthermore, prioritizing early detection, diagnosis, and treatment through the assessment of thyroid function in individuals at high risk for developing dementia is of paramount importance. This strategy has the potential to significantly contribute to the prevention and deceleration of dementia progression.

SGLT2 Inhibitor Use and Risk of Dementia and Parkinson Disease Among Patients With Type 2 Diabetes.

Despite the mechanistic potential of sodium-glucose cotransporter 2 inhibitor (SGLT2i) to improve neurologic outcomes, the efficacy of SGLT2i in neurodegenerative disorders among patients with type 2 diabetes is not well established. This population-based cohort study aimed to investigate the association of SGLT2i use with risks of incident dementia and Parkinson disease (PD) in patients with type 2 diabetes. This was a retrospective examination of data from a cohort of 1,348,362 participants with type 2 diabetes (≥40 years), who started antidiabetic drugs from 2014 to 2019, evaluated using the Korean National Health Insurance Service Database. Propensity score matching (1:1; SGLT2i to other oral antidiabetic drugs [OADs]) produced a cohort of 358,862 participants. Primary outcomes were the individual incidence of Alzheimer disease (AD), vascular dementia (VaD), and PD. Secondary outcomes were all-cause dementia (AD, VaD, and other dementia) and a composite of all-cause dementia and PD. Cox proportional hazards models were used to investigate the association between SGLT2i use and the risks of dementia and PD. From the 358,862 participants analyzed (mean [SD] age, 57.8 [9.6] years; 58.0% male), 6,837 incident dementia or PD events occurred. Regarding the individual endpoints, SGLT2i use was associated with reduced risks of AD (adjusted hazard ratio [aHR] 0.81, 95% CI 0.76-0.87), VaD (aHR 0.69, 95% CI 0.60-0.78), and PD (aHR 0.80, 95% CI 0.69-0.91) with a 6-month drug use lag period. In addition, use of SGLT2i was associated with a 21% lower risk of all-cause dementia (aHR 0.79, 95% CI 0.69-0.90) and a 22% lower risk of all-cause dementia and PD than use of other OADs (aHR 0.78, 95% CI 0.73-0.83). The association between the use of SGLT2i and the lowered risk of these neurodegenerative disorders was not affected by sex, Charlson Comorbidity Index, diabetic complications, comorbidities, and medications. Sensitivity analysis further adjusting for bioclinical variables from health screening tests, including blood pressure, glucose, lipid profiles, and kidney function, yielded generally consistent results. In this nationwide population-based study, SGLT2i use significantly reduced the risks of neurodegenerative disorders in patients with type 2 diabetes independent of various factors including comorbidities and bioclinical parameters. This study provides Class II evidence that SGLT2 antidiabetic drugs decrease the risk of dementia and PD in people with diabetes.

Associations of metabolic syndrome with cognitive function and dementia risk: Evidence from the UK Biobank cohort.

To investigate the associations of metabolic syndrome (MetS) with cognitive function, dementia and its subtypes. Based on the participants recruited by UK Biobank, this study aims to investigate the associations of MetS with cognitive function, dementia and its subtypes. Generalized estimating equations, Cox proportional risk models, and multiple linear regression models were respectively used to assess associations between MetS and dementia-related outcomes. Among the 363,231 participants, 95,713 had MetS at baseline. The results showed that MetS was significantly associated with cognitive function related to fluid intelligence and prospective memory at follow-up. Among participants aged ≥60 years, MetS was correlated with elevated risk of all-cause dementia, particularly vascular dementia (VaD) [hazard ratio 1.115 (95% confidence interval: 1.047, 1.187), hazard ratio 1.393 (95% confidence interval: 1.233, 1.575), respectively]. With increasing MetS components, the risk of all-cause dementia and VaD tended to be elevated. MetS has also been associated with dementia-related structural changes in the brain, including alterations in overall brain volume, white matter volume, grey matter volume and white matter integrity. MetS was associated with poorer cognitive performance and might increase the risk of all-cause dementia as well as VaD, but the effect on Alzheimer's disease was not significant. Holistic control of the MetS may benefit the prevention and control of cognitive impairment and dementia.

Causal association between blood leukocyte counts and vascular dementia: a two-sample bidirectional Mendelian randomization study

While previous observational studies have suggested a link between leukocyte counts and vascular dementia (VD), the causal relationship between leukocyte counts and various subtypes of VD remains elusive. This study aimed to investigate the causal relationship between five types of leukocyte counts and VD, with the goal of improving prevention and treatment strategies. In this study, leukocyte counts were used as the exposure variable, with genome-wide association study (GWAS) data sourced from both the UK Biobank and the Blood Cell Consortium. Additionally, GWAS data for five subtypes of vascular dementia were obtained from the FinnGen database. We conducted rigorous statistical analysis and visualization using Mendelian randomization (MR) to elucidate the potential causal relationship between leukocyte counts and vascular dementia. This study, utilizing MR analysis with data from the UK Biobank and Blood Cell Consortium, identified significant causal associations between increased lymphocyte counts and VD. Specifically, lymphocyte counts were found to be causally related to multiple and mixed VD subtypes. Sensitivity analyses, including MR-Egger regression and MR-PRESSO tests, confirmed the robustness of these findings, with no evidence of reverse causality or significant horizontal pleiotropy detected. The results underscore a potential inflammatory or immunological mechanism in the pathogenesis of VD, highlighting lymphocytes as a key component in their etiology. This investigation establishes a robust association between elevated lymphocyte and leukocyte counts and an increased risk of VD, emphasizing the roles of inflammation, immune activation, and hematological factors in disease pathogenesis.

Effect of Different Durations of Treatment With Antihypertensive Drugs With Anticholinergic Effects on the Risk of Dementia: A Target Trial Emulation Study.

Studying the effect of duration of treatment on prognostic outcomes using real-world data is challenging because only people who survive for a long time can receive a treatment for a long time. Specifying a target trial helps overcome such challenge. We aimed to estimate the effect of different durations of treatment with antihypertensive drugs with anticholinergic properties (AC AHT) on the risk of vascular dementia and Alzheimer's disease by emulating a target trial using the UK CPRD GOLD database (2001-2017). Comparing treatment for 3-6 years versus ≤3 years yielded null results for both types of dementia. Comparing a longer duration of treatment, >6 years versus ≤3 years, yielded a 10-year risk ratio of 0.69 (95% CI, 0.54-0.90) for vascular dementia and 0.91 (95% CI, 0.77-1.10) for Alzheimer's disease. For illustration, we performed an analysis that failed to emulate a target trial by assigning exposure categories using post-baseline information, obtaining implausible beneficial estimates. Our findings indicate a modest benefit of longer duration of treatment with AC AHT on vascular dementia and highlight the value of the target trial emulation to avoid selection bias in the evaluation of the effect of different durations of treatment.

Visual Impairment, Eye Conditions, and Diagnoses of Neurodegeneration and Dementia

Vision and eye conditions are associated with increased risk for Alzheimer disease and related dementias (ADRDs), but the nature of the association and the underlying biological pathways remain unclear. If causal, vision would be an important modifiable risk factor with viable population-level interventions. To evaluate potentially causal associations between visual acuity, eye conditions (specifically cataracts and myopia), neuroimaging outcomes, and ADRDs. A cohort and 2-sample bidirectional mendelian randomization (MR) study was conducted using UK Biobank participants and summary statistics from previously published genome-wide association studies on cataract, myopia, and AD. The participants included in the analysis were aged 55 to 70 years without dementia at baseline (calendar years 2006 to 2010), underwent genotyping, and reported on eye conditions; a subset completed visual acuity examinations (n = 69 852-71 429) or brain imaging (n = 36 591-36 855). Data were analyzed from August 15, 2022, through November 28, 2023. Self-reported cataracts, visual acuity, and myopia measured by refraction error. ADRD, AD, and vascular dementia were identified from electronic medical records. Total and regional brain volumes were determined using magnetic resonance imaging. The sample included 304 953 participants (mean [SD] age, 62.1 (4.1) years; 163 825 women [53.72%]); 14 295 (4.69%) had cataracts and 2754 (3.86%) had worse than 20/40 vision. Cataracts (hazard ratio [HR], 1.18; 95% CI, 1.07-1.29) and myopia (HR, 1.35; 95% CI, 1.06-1.70) were associated with a higher hazard of ADRD. In MR analyses to estimate potential causal effects, cataracts were associated with increased risk of vascular dementia (inverse variance-weighted odds ratio [OR], 1.92; 95% CI, 1.26-2.92) but were not associated with increased dementia (OR, 1.21; 95% CI, 0.98-1.50). There were no associations between myopia and dementia. In MR for potential reverse causality, AD was not associated with cataracts (inverse variance-weighted OR, 0.99; 95% CI, 0.96-1.01). Genetic risk for cataracts was associated with smaller total brain (β = -597.43 mm3; 95% CI, -1077.87 to -117.00 mm3) and gray matter (β = -375.17 mm3; 95% CI, -680.10 to -70.24 mm3) volumes, but not other brain regions. In this cohort and MR study of UK Biobank participants, cataracts were associated with increased risk of dementia, especially vascular dementia, and reduced total brain volumes. These findings lend further support to the hypothesis that cataract extraction may reduce the risk for dementia.

The association between urinary sodium and the risk of dementia: Evidence from a population-based cohort study

BackgroundSodium intake reduction is crucial for cardiovascular health, however, its lasting impact on dementia remains unclear. MethodsWe included 458,577 UK Biobank participants without dementia at baseline. We estimated 24-h urinary sodium (E24hUNa) using spot urinary parameters and obtained the incidence of all-cause dementia, Alzheimer's disease, and vascular dementia from multiple sources. ResultsThe mean E24hUNa was 3.0 g (1st-99th percentile: 1.5 g–5.1 g). Over a mean follow-up of 13.6 years, 7886 (1.7 %) participants developed all-cause dementia, including 3763 (0.8 %) Alzheimer's disease and 1851 (0.4 %) vascular dementia. In the restricted cubic spline model, we identify a potential cutoff of 3.13 g for E24hUNa, below which each 1 g decrease in E24hUNa was associated with 21 % (95 % confidence interval [CI] 1.11–1.34) higher all-cause dementia risk and 35 % (95 % CI 1.11–1.63) higher vascular dementia risk (P-value <0.001 for non-linearity). The hazard ratios were 1.15 (95 % CI, 1.07–1.24) for all-cause dementia and 1.21 (95 % CI 1.04–1.40) for vascular dementia among individuals with E24hUNa below 3.13 g compared to those with E24hUNa higher than 3.13 g. LimitationsOne of the major limitations is the estimation of 24-h urinary sodium with spot urine samples. ConclusionsAn E24hUNa level below 3.13 g, equivalent to 3.37 g daily sodium intake, is associated with increased risks of all-cause and vascular dementia. This exploratory study suggests a potential lower limit below which the risk of dementia increases with a lower sodium level. Future studies are necessary to validate our findings.

Association of MAFLD and MASLD with all-cause and cause-specific dementia: a prospective cohort study

BackgroundLiver disease and dementia are both highly prevalent and share common pathological mechanisms. We aimed to investigate the associations between metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of all-cause and cause-specific dementia.MethodsWe conducted a prospective study with 403,506 participants from the UK Biobank. Outcomes included all-cause dementia, Alzheimer’s disease, and vascular dementia. Multivariable Cox proportional hazards models were used for analyses.Results155,068 (38.4%) participants had MAFLD, and 111,938 (27.7%) had MASLD at baseline. During a median follow-up of 13.7 years, 5,732 participants developed dementia (2,355 Alzheimer’s disease and 1,274 vascular dementia). MAFLD was associated with an increased risk of vascular dementia (HR 1.32 [95% CI 1.18–1.48]) but a reduced risk of Alzheimer’s disease (0.92 [0.84–1.0]). Differing risks emerged among MAFLD subtypes, with the diabetes subtype increasing risk of all-cause dementia (1.8 [1.65–1.96]), vascular dementia (2.95 [2.53–3.45]) and Alzheimer’s disease (1.46 [1.26–1.69]), the lean metabolic disorder subtype only increasing vascular dementia risk (2.01 [1.25–3.22]), whereas the overweight/obesity subtype decreasing risk of Alzheimer’s disease (0.83 [0.75–0.91]) and all-cause dementia (0.9 [0.84–0.95]). MASLD was associated with an increased risk of vascular dementia (1.24 [1.1–1.39]) but not Alzheimer’s disease (1.0 [0.91–1.09]). The effect of MAFLD on vascular dementia was consistent regardless of MASLD presence, whereas associations with Alzheimer’s disease were only present in those without MASLD (0.78 [0.67–0.91]).ConclusionsMAFLD and MASLD are associated with an increased risk of vascular dementia, with subtype-specific variations observed in dementia risks. Further research is needed to refine MAFLD and SLD subtyping and explore the underlying mechanisms contributing to dementia risk.

Role of the vessel morphology on the lenticulostriate arteries hemodynamics during atrial fibrillation: A CFD-based multivariate regression analysis

Background and objectiveAtrial fibrillation (AF) is the most common cardiac arrhythmia, inducing accelerated and irregular beating. Beside well-known disabling symptoms - such as palpitations, reduced exercise tolerance, and chest discomfort - there is growing evidence that an alteration of deep cerebral hemodynamics due to AF increases the risk of vascular dementia and cognitive impairment, even in the absence of clinical strokes. The alteration of deep cerebral circulation in AF represents one of the least investigated among the possible mechanisms. Lenticulostriate arteries (LSAs) are small perforating arteries mainly departing from the middle cerebral artery (MCA) and susceptible to small vessel disease, which is one of the mechanisms of subcortical vascular dementia development. The purpose of this study is to investigate the impact of different LSAs morphologies on the cerebral hemodynamics during AF. MethodsBy combining a computational fluid dynamics (CFD) analysis of LSAs with 7T high-resolution magnetic resonance imaging (MRI), we performed different CFD-based multivariate regression analyses to detect which geometrical and morphological vessel features mostly affect AF hemodynamics in terms of wall shear stress. We exploited 17 cerebral 7T-MRI derived LSA vascular geometries extracted from 10 subjects and internal carotid artery data from validated 0D cardiovascular-cerebral modeling as inflow conditions. ResultsOur results revealed that few geometrical variables - namely the size of the MCA and the bifurcation angles between MCA and LSA - are able to satisfactorily predict the AF impact. In particular, the present study indicates that LSA morphologies exhibiting markedly obtuse LSA-MCA inlet angles and small MCA size downstream of the LSA-MCA bifurcation may be more prone to vascular damage induced by AF. ConclusionsThe present MRI-based computational study has been able for the first time to: (i) investigate the net impact of LSAs vascular morphologies on cerebral hemodynamics during AF events; (ii) detect which combination of morphological features worsens the hemodynamic response in the presence of AF. Awaiting necessary clinical confirmation, our analysis suggests that the local hemodynamics of LSAs is affected by their geometrical features and some LSA morphologies undergo greater hemodynamic alterations in the presence of AF.

Sleep Disorders and Dementia Risk in Older Patients with Kidney Failure: A Retrospective Cohort Study.

Community-dwelling older adults with sleep disorders are at higher risk of developing dementia. Greater than 50% of older patients with kidney failure experience sleep disorders, which may explain their high burden of dementia. Among 216,158 patients (age ≥66 years) with kidney failure (United States Renal Data System; 2008-2019), we estimated the risk of dementia (including subtypes) associated with sleep disorders using Cox proportional-hazard models with propensity score weighting. We tested whether positive airway pressure (PAP) therapy was associated with reduced dementia risk among patients with obstructive sleep apnea (OSA). 26.3% of patients were diagnosed with sleep disorders; these patients had a higher five-year unadjusted cumulative incidence for any type of dementia (36.2% vs. 32.3%; P<0.001), vascular dementia (4.4% vs. 3.7%; P<0.001), and other/mixed dementia (29.3% vs. 25.8%; P<0.001). Higher risk of any type of dementia was identified in patients with insomnia (aHR=1.42; 95%CI: 1.34-1.51), sleep-related breathing disorders (SRBDs) (aHR=1.20; 95%CI: 1.17-1.23), and other sleep disorders (aHR=1.24; 95%CI: 1.11-1.39). Higher vascular dementia risk was observed in patients with insomnia (aHR=1.43; 95%CI: 1.19-1.73), SRBDs (aHR=1.15; 95%CI: 1.07-1.24). Patients with SRBDs (aHR=1.07; 95%CI: 1.00-1.15) were at higher risk of Alzheimer's disease. Among patients with OSA, PAP therapy was associated with lower risk for any type of dementia (aHR=0.82; 95%CI: 0.76-0.90), and vascular dementia (aHR=0.65; 95%CI: 0.50-0.85). Older patients with kidney failure and sleep disorders are at a higher risk of dementia. Sleep is an important modifiable factor that should be considered for targeted interventions to mitigate dementia risk in patients with kidney failure. For patients with OSA, PAP therapy is associated with lower dementia risk.

The Increased Burden of Morbidity Over the Life-Course Among Patients with COPD: A Register-Based Cohort Study in Sweden.

Patients with a diagnosis of chronic obstructive pulmonary disease (COPD) often have other chronic disorders. This study aims to describe the life-course pattern of morbidity in patients with COPD. Among all residents aged 50-90 years in Sweden in 1997, people with a hospital COPD diagnosis were identified using Swedish national registers (1997-2018). Each patient with COPD was matched by sex, birthyear and county of residency with up to five COPD-free controls. Other chronic disease diagnoses were identified during 1987-2018. Conditional logistic regression calculated risk of diseases diagnosed prior to first COPD diagnosis, producing odds ratios (OR) and 95% confidence intervals (95% CI). Cox regression estimated risk of diagnoses after first COPD diagnosis, producing hazard ratios (HR) and 95% CI. Among 2,706,814 individuals, 225,159 (8.3%) had COPD. The nested case-control sample included 223,945 COPD-cases with 1,062,731 controls. Prior to first COPD diagnosis, future COPD patients had higher risks than controls for most examined conditions. Highest risks were seen for chronic heart failure (OR = 3.25, 3.20-3.30), peripheral arterial disease (OR = 3.12, 3.06-3.18) and lung cancer (OR = 12.73, 12.12-13.37). Following the COPD diagnosis, individuals with COPD had higher risks of most conditions than individuals without COPD. Chronic heart failure (HR = 3.50, 3.46-3.53), osteoporosis (HR = 3.35, 3.30-3.42), depression (HR = 2.58, 2.53-2.64) and lung cancer (HR = 6.04, 5.90-6.18) predominated. The risk of vascular dementia was increased after COPD diagnosis (HR = 1.53, 1.48-1.58) but not Alzheimer's disease. Accumulation of chronic morbidity may precede COPD. Following the diagnosis, an increased burden of cardiovascular disease and cancer is to be expected, but subsequent depression, osteoporosis, and vascular dementia should also be noted. Management strategies for patients with COPD should consider the higher-than-average risk of multimorbidity.

Association between COVID-19 and the Risk of Vascular Dementia: A Mendelian Randomisation Study of the Potential Cognitive Sequela of COVID-19.

A growing body of observational studies and Mendelian Randomisation analyses suggest an increased risk of Alzheimer's disease and dementia following COVID-19 infection. However, evidence on the potential association between COVID-19 and vascular dementia, which is plausible given the vascular complications of COVID-19 infection, is still limited. In this study, we conducted a two-sample Mendelian Randomisation analysis to examine the potential causal relationship between COVID-19 phenotypes and the risk of vascular dementia, using summary data from large-scale GWASs. The two-sample Mendelian Randomisation analysis did not detect any significant associations of COVID-19 infection, COVID-19 hospitalisation, or critical COVID-19 with the risk of vascular dementia, with weighted average β values of -0.29 (95% CI: -0.84, 0.26; p = 0.301), -0.12 (95% CI: -0.36, 0.13; p = 0.345), and -0.07 (95% CI: -0.23, 0.09; p = 0.374), respectively. Our findings do not support the hypothesis that vascular dementia is one of the long-term sequelae of COVID-19.

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.

CCR2+ monocytes promote white matter injury and cognitive dysfunction after myocardial infarction

Survivors of myocardial infarction are at increased risk for vascular dementia. Neuroinflammation has been implicated in the pathogenesis of vascular dementia, yet little is known about the cellular and molecular mediators of neuroinflammation after myocardial infarction. Using a mouse model of myocardial infarction coupled with flow cytometric analyses and immunohistochemistry, we discovered increased monocyte abundance in the brain after myocardial infarction, which was associated with increases in brain-resident perivascular macrophages and microglia. Myeloid cell recruitment and activation was also observed in post-mortem brains of humans that died after myocardial infarction. Spatial and single cell transcriptomic profiling of brain-resident myeloid cells after experimental myocardial infarction revealed increased expression of monocyte chemoattractant proteins. In parallel, myocardial infarction increased crosstalk between brain-resident myeloid cells and oligodendrocytes, leading to neuroinflammation, white matter injury, and cognitive dysfunction. Inhibition of monocyte recruitment preserved white matter integrity and cognitive function, linking monocytes to neurodegeneration after myocardial infarction. Together, these preclinical and clinical results demonstrate that monocyte infiltration into the brain after myocardial infarction initiate neuropathological events that lead to vascular dementia.

Coffee and tea consumption and dementia risk: The role of sex and vascular comorbidities

Coffee and tea consumption and dementia risk: The role of sex and vascular comorbidities

Modulation of the Circadian Rhythm and Oxidative Stress as Molecular Targets to Improve Vascular Dementia: A Pharmacological Perspective.

The circadian rhythms generated by the master biological clock located in the brain's hypothalamus influence central physiological processes. At the molecular level, a core set of clock genes interact to form transcription-translation feedback loops that provide the molecular basis of the circadian rhythm. In animal models of disease, a desynchronization of clock genes in peripheral tissues with the central master clock has been detected. Interestingly, patients with vascular dementia have sleep disorders and irregular sleep patterns. These alterations in circadian rhythms impact hormonal levels, cardiovascular health (including blood pressure regulation and blood vessel function), and the pattern of expression and activity of antioxidant enzymes. Additionally, oxidative stress in vascular dementia can arise from ischemia-reperfusion injury, amyloid-beta production, the abnormal phosphorylation of tau protein, and alterations in neurotransmitters, among others. Several signaling pathways are involved in the pathogenesis of vascular dementia. While the precise mechanisms linking circadian rhythms and vascular dementia are still being studied, there is evidence to suggest that maintaining healthy sleep patterns and supporting proper circadian rhythm function may be important for reducing the risk of vascular dementia. Here, we reviewed the main mechanisms of action of molecular targets related to the circadian cycle and oxidative stress in vascular dementia.

Developmental priming of early cerebrovascular ageing: Implications across a lifetime.

Neurological conditions such as Alzheimer's disease and stroke represent a substantial health burden to the world's ageing population. Cerebrovascular dysfunction is a key contributor to these conditions, affecting an individual's risk profile, age of onset, and severity of neurological disease. Recent data shows that early-life events, such as maternal health during pregnancy, birth weight and exposure to environmental toxins can 'prime' the vascular system for later changes. With age, blood vessels can become less flexible and more prone to damage. This can lead to reduced blood flow to the brain, which is associated with cognitive decline and an increased risk of stroke and other cerebrovascular diseases. These in turn increase the risk of vascular dementia and Alzheimer's disease. We aim to explore how early life factors influence cerebrovascular health, ageing and disease. We have reviewed recently published literature from epidemiological studies, clinical cases and basic research which explore mechanisms that contribute to cerebrovascular and blood-brain barrier dysfunction, with a particularly focus on those that assess contribution of early-life events or vascular priming to subsequent injury. Perinatal events have been linked to acute cerebrovascular dysfunction and long-term structural reorganisation. Systemic disease throughout the lifetime that produce inflammatory or oxidative stress may further sensitise the cerebrovasculature to disease and contribute to neurodegeneration. By identifying these early-life determinants and understanding their mechanisms, scientists aim to develop strategies for preventing or mitigating cerebrovascular ageing-related issues.

Circulating cytokines and vascular dementia: A bi-directional Mendelian randomization study

Inflammatory responses are associated with the development of vascular dementia (VaD). Circulating cytokines modulate the inflammatory response and are important for the immune system. To further elucidate the role of the immune system in VaD, we used Mendelian randomization (MR) to comprehensively and bi-directionally assess the role of circulating cytokines in VaD.Using state-of-the-art genome-wide association studies, we primarily assessed whether different genetic levels of 41 circulating cytokines affect the risk of developing VaD and, in turn, whether the genetic risk of VaD affects these circulating cytokines. We used inverse variance weighting (IVW) and several other MR methods to assess the bidirectional causality between circulating cytokines and VaD, and performed sensitivity analyses.Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was inversely associated with VaD risk [odds ratio (OR): 0.74, 95 % confidence interval (CI): 0.60–0.92, P = 0.007, 0.007]. VaD was associated with seven circulating cytokines: macrophage inflammatory protein 1b (MIP-1 beta) [OR: 1.05, 95 % CI: 1.01–1.08, P = 0.009], Interleukin-12p70 (IL-12) [OR: 1.04, 95 % CI: 1.00–1.08, P = 0.047], Interleukin-17 (IL-17) [OR: 1.04, 95 % CI: 1.00–1.07, P = 0.038], Interleukin-7 (IL-7) [OR: 1.07, 95 % CI: 1.02–1.12, P = 0.009], Interferon gamma (IFN-γ) [OR: 1.03, 95 % CI: 1.00–1.07, P = 0.046], Granulocyte-colony stimulating factor (GCSF) [OR: 1.06, 95 % CI: 1.02–1.09, P = 0.001], Fibroblast growth factor (FGF) [P = 0.001], and Fibroblast growth factor (FGF) [P = 0.001]. Fibroblast growth factor basic (FGF-Basic) [OR: 1.04, 95 % CI: 1.01–1.08, P = 0.02] were positively correlated.Circulating cytokines are associated with VaD, and further studies are needed to determine whether they are effective targets for intervention to prevent or treat VaD.

Causal Association Between Allergic Diseases and Dementia: Evidence from Multivariate Mendelian Randomization Study.

The link between allergic diseases and dementia remains controversial, and the genetic causality of this link is unclear. This study investigated the causal relationship between allergic diseases and dementia using univariate and multivariate Mendelian randomization (MR) methods. We selected genome-wide association studies including 66,645 patients with allergic diseases and 12,281 patients with dementia, with statistical datasets derived from the FinnGen Consortium of European origin. After a rigorous screening process for single nucleotide polymorphisms to eliminate confounding effects, MR estimation was performed mainly using the inverse variance weighting method and the MR-Egger method. Sensitivity analyses were performed using Cochran's Q test, MR-PRESSO test, MR Pleiotropy residuals and leave-one-out analysis. Univariate and multivariate MR together demonstrated a causal relationship between atopic dermatitis and reduced vascular dementia (VaD) risk (OR = 0.89, 95% CI: 0.81-0.99, p = 0.031; OR = 0.85, 95% CI: 0.76-0.95, p = 0.003). MVMR confirmed asthma was associated with a reduction in the risk of Alzheimer's disease (AD) (OR = 0.82, 95% CI: 0.71-0.94, p = 0.005) and may be associated with a reduction in the risk of VaD (OR = 0.80, 95% CI: 0.65-0.99, p = 0.042); allergic rhinitis may be causally associated with an increased risk of AD (OR = 1.16, 95% CI: 1.00-1.35, p = 0.046) and VaD (OR = 1.29, 95% CI: 1.03-1.62, p = 0.027). In sensitivity analyses, these findings were reliable. MR methods have only demonstrated that allergic rhinitis dementia is associated with an increased risk of developing dementia. Previously observed associations between other allergic diseases and dementia may be influenced by comorbidities and confounding factors rather than causality.