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BMC Oral Health May 2024Observational studies have explored the relationships of periodontitis with brain atrophy and cognitive impairment, but these findings are limited by reverse causation,...
BACKGROUND
Observational studies have explored the relationships of periodontitis with brain atrophy and cognitive impairment, but these findings are limited by reverse causation, confounders and have reported conflicting results. Our study aimed to investigate the causal associations of periodontitis with brain atrophy and cognitive impairment through a comprehensive bidirectional Mendelian randomization (MR) research.
METHODS
We incorporated two distinct genome-wide association study (GWAS) summary datasets as an exploration cohort and a replication cohort for periodontitis. Four and eight metrics were selected for the insightful evaluation of brain atrophy and cognitive impairment, respectively. The former involved cortical thickness and surface area, left and right hippocampal volumes, with the latter covering assessments of cognitive performance, fluid intelligence scores, prospective memory, and reaction time for mild cognitive impairment to Alzheimer's disease (AD), Lewy body dementia, vascular dementia and frontotemporal dementia for severe situations. Furthermore, supplementary analyses were conducted to examine the associations between the longitudinal rates of change in brain atrophy and cognitive function metrics with periodontitis. The main analysis utilized the inverse variance weighting (IVW) method and evaluated the robustness of the results through a series of sensitivity analyses. For multiple tests, associations with p-values < 0.0021 were considered statistically significant, while p-values ≥ 0.0021 and < 0.05 were regarded as suggestive of significance.
RESULTS
In the exploration cohort, forward and reverse MR results revealed no causal associations between periodontitis and brain atrophy or cognitive impairment, and only a potential causal association was found between AD and periodontitis (IVW: OR = 0.917, 95% CI from 0.845 to 0.995, P = 0.038). Results from the replication cohort similarly corroborated the absence of a causal relationship. In the supplementary analyses, the longitudinal rates of change in brain atrophy and cognitive function were also not found to have causal relationships with periodontitis.
CONCLUSIONS
The MR analyses indicated a lack of substantial evidence for a causal connection between periodontitis and both brain atrophy and cognitive impairment.
Topics: Humans; Periodontitis; Atrophy; Mendelian Randomization Analysis; Cognitive Dysfunction; Brain; Genome-Wide Association Study; Male; Female; Aged
PubMed: 38755584
DOI: 10.1186/s12903-024-04367-7 -
PloS One 2024Strategies to prevent or delay Alzheimer's disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet...
Strategies to prevent or delay Alzheimer's disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet the effects of different BP control strategies across the life course on AD/ADRD are unknown. Randomized trials may be infeasible due to prolonged follow-up and large sample sizes. Simulation analysis is a practical approach to estimating these effects using the best available existing data. However, existing simulation frameworks cannot estimate the effects of BP control on both dementia and cardiovascular disease. This manuscript describes the design principles, implementation details, and population-level validation of a novel population-health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG) study of the effect of BP levels over the life course on dementia and cardiovascular disease. MICROSIM is an agent-based Monte Carlo simulation designed using computer programming best practices. MICROSIM estimates annual vascular risk factor levels and transition probabilities in all-cause dementia, stroke, myocardial infarction, and mortality in a nationally representative sample of US adults 18+ using the National Health and Nutrition Examination Survey (NHANES). MICROSIM models changes in risk factors over time, cognition and dementia using changes from a pooled dataset of individual participant data from 6 US prospective cardiovascular cohort studies. Cardiovascular risks were estimated using a widely used risk model and BP treatment effects were derived from meta-analyses of randomized trials. MICROSIM is an extensible, open-source framework designed to estimate the population-level impact of different BP management strategies and reproduces US population-level estimates of BP and other vascular risk factors levels, their change over time, and incident all-cause dementia, stroke, myocardial infarction, and mortality.
Topics: Humans; Michigan; Chronic Disease; Computer Simulation; Male; Dementia; Aged; Female; Risk Factors; Monte Carlo Method; Blood Pressure; Middle Aged; Cardiovascular Diseases; Adult; Alzheimer Disease; Aged, 80 and over
PubMed: 38753617
DOI: 10.1371/journal.pone.0300005 -
Frontiers in Aging Neuroscience 2024Global research hotspots and future research trends in the neurobiological mechanisms of late-life depression (LLD) as well as its diagnosis and treatment are not yet...
BACKGROUND
Global research hotspots and future research trends in the neurobiological mechanisms of late-life depression (LLD) as well as its diagnosis and treatment are not yet clear.
OBJECTIVES
This study profiled the current state of global research on LLD and predicted future research trends in the field.
METHODS
Literature with the subject term LLD was retrieved from the Web of Science Core Collection, and CiteSpace software was used to perform econometric and co-occurrence analyses. The results were visualized using CiteSpace, VOSviewer, and other software packages.
RESULTS
In total, 10,570 publications were included in the analysis. Publications on LLD have shown an increasing trend since 2004. The United States and the University of California had the highest number of publications, followed consecutively by China and England, making these countries and institutions the most influential in the field. Reynolds, Charles F. was the author with the most publications. The was the journal with the most articles and citations. According to the co-occurrence analysis and keyword/citation burst analysis, cognitive impairment, brain network dysfunction, vascular disease, and treatment of LLD were research hotspots.
CONCLUSION
Late-life depression has attracted increasing attention from researchers, with the number of publications increasing annually. However, many questions remain unaddressed in this field, such as the relationship between LLD and cognitive impairment and dementia, or the impact of vascular factors and brain network dysfunction on LLD. Additionally, the treatment of patients with LLD is currently a clinical challenge. The results of this study will help researchers find suitable research partners and journals, as well as predict future hotspots.
PubMed: 38752209
DOI: 10.3389/fnagi.2024.1393110 -
Frontiers in Pharmacology 2024The dementia epidemic, attributed to aging populations, represents a growing socio-economic burden. It is estimated that in 2019 about 55 million people worldwide were... (Review)
Review
The dementia epidemic, attributed to aging populations, represents a growing socio-economic burden. It is estimated that in 2019 about 55 million people worldwide were living with dementia. With many possible causes of dementia and the possibility of mixed dementia combining Alzheimer's disease (AD) and vascular dementia the question is whether diagnostic uncertainty exists or whether diagnostic constructs based on single etiologies are incorrect. Vascular Cognitive Impairment and Dementia (VCID) designates the extent of cognitive dysfunctions from the most benign state to that of dementia, of vascular origin. We reviewed epidemiological, pathophysiological and clinical data on VCID with a focus on VaD, as well as key data on the development of a new therapeutic solution, SaiLuoTong (MLC-SLT). From documentary research executed on different web sources (PubMed, Clintrials.gov, Z-library and Google), our initial selection for the short review of VCID and VaD was based on keywords contained in each paragraph subtitles of this article with exclusion of publications in a language other than English or published before 2010. For the review of SaiLuoTong development, there was just the language exclusion criterion. Sorted by relevance and publication date, 47 references were selected from 140 shortlisted for review. With new evidence-based classification systems, vascular cognitive impairment was proposed as umbrella term covering all forms of cognitive deficits related to vascular causes. The scope of application expanded with the VCID which includes VaD and mixed pathologies. No drugs are approved for the treatment of VaD by major Western regulatory agencies, while some traditional Chinese medicines are registered in China. VCID treatment should have a dual focus: managing the underlying cerebrovascular disease and dementia symptoms. This is the objective set for the development of the MLC-SLT, the essential data of which are reviewed in detail. To strengthen VCID and VaD research, consensus groups should attempt to consolidate scattered local research initiatives into coordinated international programs. In two VaD clinical trials, MLC-SLT improved cognitive symptoms and activities of daily living, with good safety and potential disease-modifying effect. In a placebo-controlled study in 325 patients with mild to moderate VaD and randomized according to a delayed-start design, MLC-SLT demonstrated significant improvement in memory tests and performance in executive function tasks, expanding its place in the management of VCID. At week 26, changes in VADAS-cog scores (SD) from baseline were 23.25 (0.45) for MLC-SLT 180 mg bid), 23.05 (0.45) for MLC-SLT 120 mg bid (both < 0.0001), and 20.57 (0.45) for placebo ( = 0.15). At week 52, differences between both groups MLC-SLT and placebo were 2.67 and 2.48, respectively ( < 0.0001), without significant difference between MLC-SLT groups.
PubMed: 38751782
DOI: 10.3389/fphar.2024.1343820 -
PloS One 2024Vascular dementia (VD) is a common type of dementia. This study aimed to evaluate the effects of low and high doses of lutein administration in bilateral-carotid vessel...
BACKGROUND AND AIM
Vascular dementia (VD) is a common type of dementia. This study aimed to evaluate the effects of low and high doses of lutein administration in bilateral-carotid vessel occlusion (2VO) rats.
EXPERIMENTAL PROCEDURE
The rats were divided into the following groups: the control, sham-, vehicle (2VO+V) groups, and two groups after 2VO were treated with lutein 0.5 (2VO+LUT-o.5) and 5mg/kg (2VO+LUT-5). The passive-avoidance and Morris water maze were performed to examine fear and spatial memory. The field-potential recording was used to investigate the properties of basal synaptic transmission (BST), paired-pulse ratio (PPR), as an index for measurement of neurotransmitter release, and long-term potentiation (LTP). The hippocampus was removed to evaluate hippocampal cells, volume, and MDA level.
RESULT
Treatment with low and high doses improves spatial memory and LTP impairment in VD rats, but only the high dose restores the fear memory, hippocampal cell loss, and volume and MDA level. Interestingly, low-dose, but not high-dose, increased PPR. However, BST recovered only in the high-dose treated group.
CONCLUSIONS
Treatment with a low dose might affect neurotransmitter release probability, but a high dose affects postsynaptic processes. It seems likely that low and high doses improve memory and LTP through different mechanisms.
Topics: Animals; Dementia, Vascular; Rats; Male; Neuronal Plasticity; Long-Term Potentiation; Disease Models, Animal; Hippocampus; Lutein; Memory; Rats, Wistar; Spatial Memory; Dose-Response Relationship, Drug; Maze Learning; Synaptic Transmission
PubMed: 38748711
DOI: 10.1371/journal.pone.0302850 -
The Journal of Clinical Investigation May 2024Cerebral small vessel disease (cSVD) encompasses a heterogeneous group of age-related small vessel pathologies that affect multiple regions. Disease manifestations range... (Review)
Review
Cerebral small vessel disease (cSVD) encompasses a heterogeneous group of age-related small vessel pathologies that affect multiple regions. Disease manifestations range from lesions incidentally detected on neuroimaging (white matter hyperintensities, small deep infarcts, microbleeds, or enlarged perivascular spaces) to severe disability and cognitive impairment. cSVD accounts for approximately 25% of ischemic strokes and the vast majority of spontaneous intracerebral hemorrhage and is also the most important vascular contributor to dementia. Despite its high prevalence and potentially long therapeutic window, there are still no mechanism-based treatments. Here, we provide an overview of the recent advances in this field. We summarize recent data highlighting the remarkable continuum between monogenic and multifactorial cSVDs involving NOTCH3, HTRA1, and COL4A1/A2 genes. Taking a vessel-centric view, we discuss possible cause-and-effect relationships between risk factors, structural and functional vessel changes, and disease manifestations, underscoring some major knowledge gaps. Although endothelial dysfunction is rightly considered a central feature of cSVD, the contributions of smooth muscle cells, pericytes, and other perivascular cells warrant continued investigation.
Topics: Humans; Cerebral Small Vessel Diseases; Receptor, Notch3; Collagen Type IV; High-Temperature Requirement A Serine Peptidase 1; Animals
PubMed: 38747292
DOI: 10.1172/JCI172841 -
Scientific Reports May 2024Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort...
Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02-1.09), vascular dementia (HR, 1.08; 95% CI 1.01-1.15), and non-Alzheimer's disease non-vascular dementia (HR, 1.09; 95% CI 1.03-1.14). No significant association was observed for Alzheimer's disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia.
Topics: Humans; Female; Male; United Kingdom; Dementia; Family Characteristics; Middle Aged; Biological Specimen Banks; Aged; Risk Factors; Prospective Studies; Incidence; Proportional Hazards Models; Brain; UK Biobank
PubMed: 38744903
DOI: 10.1038/s41598-024-61102-6 -
BMC Public Health May 2024New effective treatments for dementia are lacking, and early prevention focusing on risk factors of dementia is important. Non-pharmacological intervention therapies...
BACKGROUND
New effective treatments for dementia are lacking, and early prevention focusing on risk factors of dementia is important. Non-pharmacological intervention therapies aimed at these factors may provide a valuable tool for reducing the incidence of dementia. This study focused on the development of a mathematical model to predict the number of individuals with neurodegenerative diseases, specifically Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis. Scenarios for non-pharmacological intervention therapies based on risk factor reduction were also assessed. The estimated total costs and potential cost savings from societal were included.
METHODS
Based on demographic and financial data from the EU, a mathematical model was developed to predict the prevalence and resulting care costs of neurodegenerative diseases in the population. Each disease (Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis) used parameters that included prevalence, incidence, and death risk ratio, and the simulation is related to the age of the cohort and the disease stage.
RESULTS
A replicable simulation for predicting the prevalence and resulting cost of care for neurodegenerative diseases in the population exhibited an increase in treatment costs from 267 billion EUR in 2021 to 528 billion EUR by 2050 in the EU alone. Scenarios related to the reduction of the prevalence of dementia by up to 20% per decade led to total discounted treatment cost savings of up to 558 billion EUR.
CONCLUSION
The model indicates the magnitude of the financial burden placed on EU healthcare systems due to the growth in the population prevalence of neurodegenerative diseases in the coming decades. Lifestyle interventions based on reducing the most common risk factors could serve as a prevention strategy to reduce the incidence of dementia with substantial cost-savings potential. These findings could support the implementation of public health approaches throughout life to ultimately prevent premature mortality and promote a healthier and more active lifestyle in older individuals.
Topics: Humans; Dementia; Risk Factors; Europe; Cost Savings; Aged; Health Care Costs; Models, Theoretical; Male; Female; Prevalence; Aged, 80 and over; Middle Aged
PubMed: 38741111
DOI: 10.1186/s12889-024-18773-7 -
Frontiers in Immunology 2024Emerging evidence has shown that gut diseases can regulate the development and function of the immune, metabolic, and nervous systems through dynamic bidirectional...
OBJECTIVE
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.
METHODS
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.
RESULTS
We screened 167 coDEGs. The main articles of coDEGs enrichment analysis focused on immune function. 8 shared hub genes were identified, including , , , , , , , and . 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.
CONCLUSIONS
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.
Topics: Humans; Inflammatory Bowel Diseases; Computational Biology; Protein Interaction Maps; Dementia, Vascular; Gene Regulatory Networks; Gene Expression Profiling; Databases, Genetic; Transcriptome; Gene Ontology
PubMed: 38736878
DOI: 10.3389/fimmu.2024.1347415 -
Journal of Obesity & Metabolic Syndrome May 2024Intermittent fasting (IF), a dietary pattern alternating between eating and fasting periods within a 24-hour cycle, has garnered recognition for its potential to enhance... (Review)
Review
Intermittent fasting (IF), a dietary pattern alternating between eating and fasting periods within a 24-hour cycle, has garnered recognition for its potential to enhance both healthspan and lifespan in animal models and humans. It also shows promise in alleviating age-related diseases, including neurodegeneration. Vascular cognitive impairment (VCI) spans a severity range from mild cognitive deficits to severe cognitive deficits and loss of function in vascular dementia. Chronic cerebral hypoperfusion has emerged as a significant contributor to VCI, instigating vascular pathologies such as microbleeds, blood-brain barrier dysfunction, neuronal loss and white matter lesions. Preclinical studies in rodents strongly suggest that IF has the potential to attenuate pathological mechanisms, including excitotoxicity, oxidative stress, inflammation, and cell death pathways in VCI models. Hence, this supports evaluating IF in clinical trials for both existing and at-risk VCI patients. This review compiles existing data supporting IF's potential in treating VCI-related vascular and neuronal pathologies, emphasizing the mechanisms by which IF may mitigate these issues. Hence providing a comprehensive overview of the available data supporting IF's potential in treating VCI by emphasizing the underlying mechanisms that make IF a promising intervention for VCI.
PubMed: 38736362
DOI: 10.7570/jomes24010