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Oxidative Medicine and Cellular... 2020It is widely accepted that inflammation may contribute to cognitive impairment in patients with vascular dementia (VD). Our prior clinical researches have reported that...
BACKGROUND
It is widely accepted that inflammation may contribute to cognitive impairment in patients with vascular dementia (VD). Our prior clinical researches have reported that acupuncture can alleviate cognitive function in VD, but the underlying mechanisms are still unclear. The purpose of this research was to explore whether acupuncture alleviates cognitive impairment by suppressing the microRNA-93- (miR-93-) mediated Toll-like receptor (TLR) signaling pathway, which triggers inflammatory responses in the central nervous system.
METHODS
VD was established by permanent bilateral common carotid artery occlusion in male Wistar rats. Three days after operation, the rats began daily treatment with acupuncture for two weeks. The levels of miR-93, Toll-like receptors (TLR2 and TLR4), intracellular signaling molecules (myeloid differentiation factor 88 (MyD88) and nuclear factor-kappa B (NF-B)), and inflammatory cytokines were subsequently detected. TLR4 colocalized with neurons, microglia, and astrocytes in the hippocampus was evaluated. Neuroinflammation and cognitive function were determined after intracerebroventricular injection of TLR4 antagonist TAK-242 or agonist lipopolysaccharide (LPS) with or without acupuncture.
RESULTS
We found that acupuncture notably repressed the expression of inflammatory cytokines in the hippocampus and plasma of VD rats. The expression of TLR4, but not TLR2, was markedly downregulated by acupuncture, accompanied by a decrease in miR-93 and MyD88/NF-B signaling pathway activation. The overexpression of TLR4 in microglia, but not in astrocytes and neurons, was reversed by acupuncture. Furthermore, intracerebroventricular injection of TAK-242 had similar effects to acupuncture on inflammation and cognitive function, while LPS injection abolished the beneficial effects of acupuncture.
CONCLUSIONS
Taken together, these findings provide evidence that acupuncture attenuates cognitive impairment associated with inflammation through inhibition of the miR-93-mediated TLR4/MyD88/NF-B signaling pathway in experimental VD. Acupuncture serves as a promising alternative therapy and may be an underlying TLR4 inhibitor for the treatment of VD.
Topics: Acupuncture Points; Acupuncture Therapy; Animals; Cognition; Dementia, Vascular; Hippocampus; Inflammation; Male; MicroRNAs; Microglia; Models, Biological; Myeloid Differentiation Factor 88; NF-kappa B; Neuroprotective Agents; Rats, Wistar; Signal Transduction; Toll-Like Receptor 2; Toll-Like Receptor 4
PubMed: 32850002
DOI: 10.1155/2020/8253904 -
Current Opinion in Hematology May 2019Microvascular ischemic disease of the brain is a common cause of cognitive impairment and dementia, particularly in the context of preexisting cardiovascular risk... (Review)
Review
PURPOSE OF REVIEW
Microvascular ischemic disease of the brain is a common cause of cognitive impairment and dementia, particularly in the context of preexisting cardiovascular risk factors and aging. This review summarizes our current understanding of the emerging molecular themes that underlie progressive and irreparable vascular disease leading to neuronal tissue injury and dementia.
RECENT FINDINGS
Cardiometabolic risk factors including diabetes and hypertension are known to contribute to vascular disease. Currently, the impact of these risk factors on the integrity and function of the brain vasculature has been target of intense investigation. Molecularly, the consequences associated with these risk factors indicate that reactive oxygen species are strong contributors to cerebrovascular dysfunction and injury. In addition, genetic linkage analyses have identified penetrant monogenic causes of vascular dementia. Finally, recent reports begun to uncover a large number of polymorphisms associated with a higher risk for cerebrovascular disease.
SUMMARY
A comprehensive picture of key risk factors and genetic predispositions that contribute to brain microvascular disease and result in vascular dementia is starting to emerge. Understanding their relationships and cross-interactions will significantly aid in the development of preventive and intervention strategies for this devastating condition.
Topics: Animals; Dementia, Vascular; Diabetes Complications; Genetic Predisposition to Disease; Humans; Hypertension; Risk Factors
PubMed: 30883434
DOI: 10.1097/MOH.0000000000000502 -
Journal of Neurochemistry Mar 2018Vascular cognitive impairment and dementia (VCID) is a major public health concern because of the increased incidence of vascular disease in the aging population and the... (Review)
Review
Vascular cognitive impairment and dementia (VCID) is a major public health concern because of the increased incidence of vascular disease in the aging population and the impact of vascular disease on Alzheimer's disease. VCID is a heterogeneous group of diseases for which there are no proven treatments. Biomarkers can be used to select more homogeneous populations. Small vessel disease is the most prevalent form of VCID and is the optimal form for treatment trials because there is a progressive course with characteristic pathological changes. Subcortical ischemic vascular disease of the Binswanger type (SIVD-BD) has a characteristic set of features that can be used both to identify patients and to follow treatment. SIVD-BD patients have clinical, neuropsychological, cerebrospinal fluid (CSF) and imaging features that can be used as biomarkers. No one feature is diagnostic, but a multimodal approach defines the SIVD-BD spectrum disorder. The most important features are large white matter lesions with axonal damage, blood-brain barrier disruption as shown by magnetic resonance imaging and CSF, and neuropsychological evidence of executive dysfunction. We have used these features to create a Binswanger Disease Scale and a probability of SIVD-BD, using a machine-learning algorithm. The patients discussed in this review are derived from published studies. Biomarkers not only aid in early diagnosis before the disease process has progressed too far for treatment, but also can indicate response to treatment. Refining the use of biomarkers will allow dementia treatment to enter the era of precision medicine. This article is part of the Special Issue "Vascular Dementia".
Topics: Biomarkers; Cognitive Dysfunction; Dementia, Vascular; Encephalitis; Humans
PubMed: 28902409
DOI: 10.1111/jnc.14218 -
Expert Review of Neurotherapeutics Oct 2014Binswanger's disease (BD) is a progressive form of cerebral small vessel disease affecting the white matter and other subcortical structures. Clinical and imaging... (Review)
Review
Binswanger's disease (BD) is a progressive form of cerebral small vessel disease affecting the white matter and other subcortical structures. Clinical and imaging characteristics, neuropsychological profile and cerebrospinal fluid analysis aid in making the diagnosis. BD shares features of other small vessel diseases and degenerative neurological conditions, which makes diagnosis difficult. However, with recent developments in MRI methods and serum/cerebrospinal fluid biomarkers, we have gained a greater understanding of the complex pathophysiology of the disease that will guide us to a more certain diagnosis. There is growing evidence that the white matter injury in BD is related to endothelial dysfunction with a secondary inflammatory response leading to breakdown of the neurovascular unit. This review summarizes current and future research directions, including pathophysiological mechanisms and potential therapeutic approaches.
Topics: Animals; Blood Vessels; Brain; Cognitive Dysfunction; Dementia, Vascular; Endothelium; Humans; Magnetic Resonance Imaging
PubMed: 25201523
DOI: 10.1586/14737175.2014.956726 -
Molecular Psychiatry Feb 2022Aging is associated with chronic systemic inflammation, which contributes to the development of many age-related diseases, including vascular disease. The world's... (Review)
Review
Aging is associated with chronic systemic inflammation, which contributes to the development of many age-related diseases, including vascular disease. The world's population is aging, leading to an increasing prevalence of both stroke and vascular dementia. The inflammatory response to ischemic stroke is critical to both stroke pathophysiology and recovery. Age is a predictor of poor outcomes after stroke. The immune response to stroke is altered in aged individuals, which contributes to the disparate outcomes between young and aged patients. In this review, we describe the current knowledge of the effects of aging on the immune system and the cerebral vasculature and how these changes alter the immune response to stroke and vascular dementia in animal and human studies. Potential implications of these age-related immune alterations on chronic inflammation in vascular disease outcome are highlighted.
Topics: Aged; Aging; Animals; Dementia, Vascular; Humans; Inflammation; Stroke
PubMed: 34711943
DOI: 10.1038/s41380-021-01361-1 -
Biochimica Et Biophysica Acta May 2016Vascular contributions to cognitive impairment are receiving heightened attention as potentially modifiable factors for dementias of later life. These factors have now... (Review)
Review
Vascular contributions to cognitive impairment are receiving heightened attention as potentially modifiable factors for dementias of later life. These factors have now been linked not only to vascular cognitive disorders but also Alzheimer's disease. In this chapter we review 3 related topics that address vascular contributions to cognitive impairment: 1. vascular pathogenesis and mechanisms; 2. neuropsychological and neuroimaging phenotypic manifestations of cerebrovascular disease; and 3. prospects for prevention of cognitive impairment of later life based on cardiovascular and stroke risk modification. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.
Topics: Animals; Brain; Cognitive Dysfunction; Dementia, Vascular; Humans; Neuroimaging; Neuropsychological Tests; Risk Factors
PubMed: 26704177
DOI: 10.1016/j.bbadis.2015.12.015 -
Ugeskrift For Laeger Mar 2017Vascular dementia comprises a heterogeneous group of conditions covering a range of clinical and neuropathological presentations of cerebrovascular disease-causing... (Review)
Review
Vascular dementia comprises a heterogeneous group of conditions covering a range of clinical and neuropathological presentations of cerebrovascular disease-causing dementia. Vascular dementia is a common occurrence, but many questions regarding the disease remain unanswered. Recently, proposed criteria focus on constructing an overarching disease concept, which captures both pre-dementia stages and the clinical and neuropathological heterogeneity. Future research should focus on identifying subtypes with distinct pathophysiological mechanisms in order to facilitate treatment development.
Topics: Dementia, Vascular; Humans; Magnetic Resonance Imaging
PubMed: 28330543
DOI: No ID Found -
BMC Medicine Mar 2023Emerging data suggests the neuroprotective and anti-neuroinflammatory effects of glucosamine. We aimed to examine the association between regular glucosamine use and...
BACKGROUND
Emerging data suggests the neuroprotective and anti-neuroinflammatory effects of glucosamine. We aimed to examine the association between regular glucosamine use and risk of incident dementia, including dementia subtypes.
METHODS
We conducted large-scale observational and two-sample Mendelian randomization (MR) analyses. Participants in UK Biobank having accessible data for dementia incidence and who did not have dementia at baseline were included in the prospective cohort. Through the Cox proportional hazard model, we examined the risks of incident all-cause dementia, Alzheimer's disease (AD), and vascular dementia among glucosamine users and non-users. To further test the causal association between glucosamine use and dementia, we conducted a 2-sample MR utilizing summary statistics from genome-wide association studies (GWAS). The GWAS data were obtained from observational cohort participants of mostly European ancestry.
RESULTS
During a median follow-up of 8.9 years, there were 2458 cases of all-cause dementia, 924 cases of AD, and 491 cases of vascular dementia. In multivariable analysis, the hazard ratios (HR) of glucosamine users for all-cause dementia, AD, and vascular dementia were 0.84 (95% CI 0.75-0.93), 0.83 (95% CI 0.71-0.98), and 0.74 (95% CI 0.58-0.95), respectively. The inverse associations between glucosamine use and AD appeared to be stronger among participants aged below 60 years than those aged above 60 years (p = 0.04 for interaction). The APOE genotype did not modify this association (p > 0.05 for interaction). Single-variable MR suggested a causal relationship between glucosamine use and lower dementia risk. Multivariable MR showed that taking glucosamine continued to protect against dementia after controlling for vitamin, chondroitin supplement use and osteoarthritis (all-cause dementia HR 0.88, 95% CI 0.81-0.95; AD HR 0.78, 95% CI 0.72-0.85; vascular dementia HR 0.73, 95% CI 0.57-0.94). Single and multivariable inverse variance weighted (MV-IVW) and MR-Egger sensitivity analyses produced similar results for these estimations.
CONCLUSIONS
The findings of this large-scale cohort and MR analysis provide evidence for potential causal associations between the glucosamine use and lower risk for dementia. These findings require further validation through randomized controlled trials.
Topics: Humans; Aged; Glucosamine; Dementia, Vascular; Genome-Wide Association Study; Mendelian Randomization Analysis; Prospective Studies; Alzheimer Disease; Polymorphism, Single Nucleotide
PubMed: 36978077
DOI: 10.1186/s12916-023-02816-8 -
Journal of the Neurological Sciences Nov 2012The epidemic growth of dementia causes great concern for the society. It is customary to consider Alzheimer's disease (AD) as the most common cause of dementia, followed... (Review)
Review
The epidemic growth of dementia causes great concern for the society. It is customary to consider Alzheimer's disease (AD) as the most common cause of dementia, followed by vascular dementia (VaD). This dichotomous view of a neurodegenerative disease as opposed to brain damage caused by extrinsic factors led to separate lines of research in these two entities. Indeed, accumulated data suggest that the two disorders have additive effects and probably interact; however it is still unknown to what degree. Furthermore, epidemiological studies have shown "vascular" risk factors to be associated with AD. Therefore, a clear distinction between AD and VaD cannot be made in most cases, and is furthermore unhelpful. In the absence of efficacious treatment for the neurodegenerative process, special attention must be given to the vascular component, even in patients with presumed mixed pathology. Symptomatic treatment of VaD and AD is similar, although the former is less effective. For prevention of dementia it is important to treat all factors aggressively, even in stroke survivors who do not show evidence of cognitive decline. In this review, we will give a clinical and pathological picture of the processes leading to VaD and discuss its interaction with AD.
Topics: Animals; Cognition Disorders; Dementia, Vascular; Humans; Risk Factors
PubMed: 22575403
DOI: 10.1016/j.jns.2012.03.027 -
Journal of Neurochemistry Mar 2018This Preface introduces the articles of the special issue on "Vascular Dementia" in which several recognized experts provide an overview of this research field. The...
This Preface introduces the articles of the special issue on "Vascular Dementia" in which several recognized experts provide an overview of this research field. The brain is a highly vascularized organ and consequently, vascular dysfunction and related pathways affect cognitive performance and memory. Vascular dementia or vascular cognitive impairment is the second most common type of dementia after Alzheimer's disease, and both disorders often occur in parallel. With this special issue, we hope to provide insight and a stimulating discussion for the future development of this research field. This article is part of the Special Issue "Vascular Dementia".
Topics: Brain; Cognitive Dysfunction; Dementia, Vascular; Humans
PubMed: 29430652
DOI: 10.1111/jnc.14287