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Molecular Neurodegeneration Jul 2023Vascular cognitive impairment and dementia (VCID) is commonly caused by vascular injuries in cerebral large and small vessels and is a key driver of age-related... (Review)
Review
Vascular cognitive impairment and dementia (VCID) is commonly caused by vascular injuries in cerebral large and small vessels and is a key driver of age-related cognitive decline. Severe VCID includes post-stroke dementia, subcortical ischemic vascular dementia, multi-infarct dementia, and mixed dementia. While VCID is acknowledged as the second most common form of dementia after Alzheimer's disease (AD) accounting for 20% of dementia cases, VCID and AD frequently coexist. In VCID, cerebral small vessel disease (cSVD) often affects arterioles, capillaries, and venules, where arteriolosclerosis and cerebral amyloid angiopathy (CAA) are major pathologies. White matter hyperintensities, recent small subcortical infarcts, lacunes of presumed vascular origin, enlarged perivascular space, microbleeds, and brain atrophy are neuroimaging hallmarks of cSVD. The current primary approach to cSVD treatment is to control vascular risk factors such as hypertension, dyslipidemia, diabetes, and smoking. However, causal therapeutic strategies have not been established partly due to the heterogeneous pathogenesis of cSVD. In this review, we summarize the pathophysiology of cSVD and discuss the probable etiological pathways by focusing on hypoperfusion/hypoxia, blood-brain barriers (BBB) dysregulation, brain fluid drainage disturbances, and vascular inflammation to define potential diagnostic and therapeutic targets for cSVD.
Topics: Humans; Dementia, Vascular; Alzheimer Disease; Causality; Risk Factors; Cerebral Small Vessel Diseases
PubMed: 37434208
DOI: 10.1186/s13024-023-00640-5 -
Journal of Cerebral Blood Flow and... Nov 2023Vascular cognitive impairment (VCI) refers to all forms of cognitive disorder related to cerebrovascular diseases, including vascular mild cognitive impairment,... (Review)
Review
Vascular cognitive impairment (VCI) refers to all forms of cognitive disorder related to cerebrovascular diseases, including vascular mild cognitive impairment, post-stroke dementia, multi-infarct dementia, subcortical ischemic vascular dementia (SIVD), and mixed dementia. Among the causes of VCI, more attention has been paid to SIVD because the causative cerebral small vessel pathologies are frequently observed in elderly people and because the gradual progression of cognitive decline often mimics Alzheimer's disease. In most cases, small vessel diseases are accompanied by cerebral hypoperfusion. In mice, prolonged cerebral hypoperfusion is induced by bilateral carotid artery stenosis (BCAS) with surgically implanted metal micro-coils. This cerebral hypoperfusion BCAS model was proposed as a SIVD mouse model in 2004, and the spreading use of this mouse SIVD model has provided novel data regarding cognitive dysfunction and histological/genetic changes by cerebral hypoperfusion. Oxidative stress, microvascular injury, excitotoxicity, blood-brain barrier dysfunction, and secondary inflammation may be the main mechanisms of brain damage due to prolonged cerebral hypoperfusion, and some potential therapeutic targets for SIVD have been proposed by using transgenic mice or clinically used drugs in BCAS studies. This review article overviews findings from the studies that used this hypoperfused-SIVD mouse model, which were published between 2004 and 2021.
Topics: Humans; Mice; Animals; Aged; Carotid Stenosis; Dementia, Vascular; Cognitive Dysfunction; Cerebrovascular Disorders; Disease Models, Animal; Brain Ischemia; Mice, Inbred C57BL
PubMed: 36883344
DOI: 10.1177/0271678X231154597 -
The EPMA Journal Dec 2022Due to the reactive medical approach applied to disease management, stroke has reached an epidemic scale worldwide. In 2019, the global stroke prevalence was 101.5...
Due to the reactive medical approach applied to disease management, stroke has reached an epidemic scale worldwide. In 2019, the global stroke prevalence was 101.5 million people, wherefrom 77.2 million (about 76%) suffered from ischemic stroke; 20.7 and 8.4 million suffered from intracerebral and subarachnoid haemorrhage, respectively. Globally in the year 2019 - 3.3, 2.9 and 0.4 million individuals died of ischemic stroke, intracerebral and subarachnoid haemorrhage, respectively. During the last three decades, the absolute number of cases increased substantially. The current prevalence of stroke is 110 million patients worldwide with more than 60% below the age of 70 years. Prognoses by the World Stroke Organisation are pessimistic: globally, it is predicted that 1 in 4 adults over the age of 25 will suffer stroke in their lifetime. Although age is the best known contributing factor, over 16% of all strokes occur in teenagers and young adults aged 15-49 years and the incidence trend in this population is increasing. The corresponding socio-economic burden of stroke, which is the leading cause of disability, is enormous. Global costs of stroke are estimated at 721 billion US dollars, which is 0.66% of the global GDP. Clinically manifested strokes are only the "tip of the iceberg": it is estimated that the total number of stroke patients is about 14 times greater than the currently applied reactive medical approach is capable to identify and manage. Specifically, lacunar stroke (LS), which is characteristic for silent brain infarction, represents up to 30% of all ischemic strokes. Silent LS, which is diagnosed mainly by routine health check-up and autopsy in individuals without stroke history, has a reported prevalence of silent brain infarction up to 55% in the investigated populations. To this end, silent brain infarction is an independent predictor of ischemic stroke. Further small vessel disease and silent lacunar brain infarction are considered strong contributors to cognitive impairments, dementia, depression and suicide, amongst others in the general population. In sub-populations such as diabetes mellitus type 2, proliferative diabetic retinopathy is an independent predictor of ischemic stroke. According to various statistical sources, cryptogenic strokes account for 15 to 40% of the entire stroke incidence. The question to consider here is, whether a cryptogenic stroke is fully referable to unidentifiable aetiology or rather to underestimated risks. Considering the latter, translational research might be of great clinical utility to realise innovative predictive and preventive approaches, potentially benefiting high risk individuals and society at large. In this position paper, the consortium has combined multi-professional expertise to provide clear statements towards the paradigm change from reactive to predictive, preventive and personalised medicine in stroke management, the crucial elements of which are:Consolidation of multi-disciplinary expertise including family medicine, predictive and in-depth diagnostics followed by the targeted primary and secondary (e.g. treated cancer) prevention of silent brain infarctionApplication of the health risk assessment focused on sub-optimal health conditions to effectively prevent health-to-disease transitionApplication of AI in medicine, machine learning and treatment algorithms tailored to robust biomarker patternsApplication of innovative screening programmes which adequately consider the needs of young populations.
PubMed: 36415625
DOI: 10.1007/s13167-022-00307-z -
Cureus Oct 2022Strokes involving specific areas regulating cognition and behavioral functions constitute strategic infarct vascular dementia. We present three patients with acute...
Strokes involving specific areas regulating cognition and behavioral functions constitute strategic infarct vascular dementia. We present three patients with acute behavioral changes and cognitive impairment following a strategic infarct. Case 1 is of a 59-year-old male, a known patient of diabetes mellitus under treatment, who presented with acute onset of memory deficit along with difficulty in recognizing faces, and left hemispatial neglect. Case 2 is of a 62-year-old male, a smoker, who presented with acute onset of behavioral abnormalities, gait apraxia, and decreased word output. Case 3 is of a 64-year-old female, a known patient of type 2 diabetes mellitus and cerebrovascular accident with left hemiparesis, who presented with psychomotor withdrawal, depression, and cautious gait. One of the most prevalent forms of dementia in adults is vascular dementia, often caused by multiple small strokes, termed multi-infarct dementia. Strategic infarct dementia, on the other hand, is usually caused by a small, single cerebral infarct. The strategic brain regions specifically involved in post-stroke cognitive impairment requires detailed clinical examination along with radiological imaging for accurate localization. Thus the cognitive impact of ischemic strokes can be understood and predicted by clinicians with the help of maps of strategic brain regions associated with global and domain-specific cognitive functions.
PubMed: 36348824
DOI: 10.7759/cureus.30009 -
Frontiers in Neurology 2022To explore the development context, research hotspots, and frontiers of acupuncture therapy for cognitive impairment (CI) from 1992 to 2022 by visualization analysis.
OBJECTIVE
To explore the development context, research hotspots, and frontiers of acupuncture therapy for cognitive impairment (CI) from 1992 to 2022 by visualization analysis.
METHODS
Articles about acupuncture therapy for cognitive impairment were retrieved from the Web of Science Core Collection (WoSCC) until 1 March 2022. Basic information was collected by Excel 2007, and VOSviewer 1.6.17 was used to analyze the co-occurrence of countries, institutes, and authors. Co-citation maps of authors and references were analyzed by CiteSpace V.5.8.R3. In addition, CiteSpace was used to analyze keyword clusters and forecast research frontiers.
RESULTS
A total of 279 articles were retrieved, including articles from 19 countries, 334 research institutes, and 101 academic journals. The most published country and institutes were the People's Republic of China (217) and the Fujian University of Traditional Chinese Medicine (40). Ronald C Petersen owned the highest co-citations (56). Keywords and co-cited references cluster showed the main research directions in this area, including "ischemic stroke," "cerebral ischemia/reperfusion," "mild cognitive impairment," "Alzheimer's disease," "vascular dementia," "vascular cognitive impairment with no dementia," "multi-infarct dementia," "synaptic injury," "functional MRI," "glucose metabolism," "NMDA," "nuclear factor-kappa b pathway," "neurotrophic factor," "matrix metalloproteinase-2 (MMP-2)," "tumor necrosis factor-alpha," "Bax," "Caspase-3," and "Noxa". Trending keywords may indicate frontier topics, such as "randomized controlled trial," "rat model," and "meta-analysis."
CONCLUSION
This research provides valuable information for the study of acupuncture. Diseases focus on mild cognitive impairment (MCI), Alzheimer's disease (AD), and vascular dementia (VaD). Tauopathies with hyperphosphorylation of Tau protein as the main lesions also need to be paid attention to. The development of functional magnetic resonance imaging (fMRI) will better explain the therapeutic effect of acupuncture treatment. The effect of acupuncture on a single point is more convincing, and acupuncture on Baihui (GV20) may be needed in the future. Finally, the implementation of high-quality multicenter randomized controlled trials (RCTs) requires increased collaboration among experts from multiple fields and countries.
PubMed: 36226080
DOI: 10.3389/fneur.2022.1006830 -
Continuum (Minneapolis, Minn.) Jun 2022This article gives a broad overview of vascular cognitive impairment and dementia, including epidemiology, pathophysiology, clinical approach, and management. Emphasis... (Review)
Review
PURPOSE OF REVIEW
This article gives a broad overview of vascular cognitive impairment and dementia, including epidemiology, pathophysiology, clinical approach, and management. Emphasis is placed on understanding the common underlying types of cerebrovascular disease (including atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy) and awareness of rare inherited cerebrovascular disorders.
RECENT FINDINGS
The pathophysiology of vascular cognitive impairment and dementia is heterogeneous, and the most recent diagnostic criteria for vascular cognitive impairment and dementia break down the diagnosis of major vascular dementia into four phenotypic categories, including subcortical ischemic vascular dementia, poststroke dementia, multi-infarct dementia, and mixed dementia. Control of cardiovascular risk factors, including management of midlife blood pressure, cholesterol, and blood sugars, remains the mainstay of prevention for vascular cognitive impairment and dementia. Cerebral amyloid angiopathy requires special consideration when it comes to risk factor management given the increased risk of spontaneous intracerebral hemorrhage. Recent trials suggest some improvement in global cognitive function in patients with vascular cognitive impairment and dementia with targeted cognitive rehabilitation.
SUMMARY
Thorough clinical evaluation and neuroimaging form the basis for diagnosis. As vascular cognitive impairment and dementia is the leading nondegenerative cause of dementia, identifying risk factors and optimizing their management is paramount. Once vascular brain injury has occurred, symptomatic management should be offered and secondary prevention pursued.
Topics: Alzheimer Disease; Cerebral Amyloid Angiopathy; Cerebrovascular Disorders; Cognitive Dysfunction; Dementia, Vascular; Humans; Neuroimaging
PubMed: 35678401
DOI: 10.1212/CON.0000000000001124 -
Frontiers in Neurology 2021Older adults with dementia have been significantly at more risk for not receiving the care needed and for developing further mental health problems during COVID-19....
Older adults with dementia have been significantly at more risk for not receiving the care needed and for developing further mental health problems during COVID-19. Although the rise in telemedicine adoption in the healthcare system has made it possible for patients to connect with their healthcare providers virtually, little is known about its use and effects among older adults with dementia and their mental health. This systematic review aimed to explore the use, accessibility, and feasibility of telemedicine in older adults with dementia, as well as examine the potential mental health impacts of these technologies, through reviewing evidence from studies conducted during COVID-19. PubMed, Scopus, and Web of Science databases were searched with the following keywords: (COVID OR SARS-CoV-2 OR Coronavirus) AND ("mental health" OR Depression OR Stress) AND (Dementia OR Multi-Infarct Dementia OR Vascular Dementia OR Frontotemporal Dementia) AND (elder OR Aging OR Aging OR Aged) AND (Telemedicine OR "Remote Consultation" OR telehealth OR technology). A total of 7 articles from Asia, Europe, and the United States were included in this review. Throughout the studies cognitive and mental health assessments (e.g., MoCA, FAST, etc.) were performed. Despite the barriers, telemedicine was noted as a feasible approach to assist individuals with dementia in connecting with their service providers and family while reducing complications related to travel (e.g., difficulty moving, traffic, distance). Due to the COVID-19 pandemic, finding alternative ways to provide services to older adults with dementia through technology may continue to become more necessary as time goes on.
PubMed: 34970210
DOI: 10.3389/fneur.2021.761965 -
International Journal of Environmental... Dec 2021Senile dementia, also known as dementia, is the mental deterioration which is associated with aging. It is characterized by a decrease in cognitive abilities, inability... (Review)
Review
Senile dementia, also known as dementia, is the mental deterioration which is associated with aging. It is characterized by a decrease in cognitive abilities, inability to concentrate, and especially the loss of higher cerebral cortex function, including memory, judgment, abstract thinking, and other loss of personality, even behavior changes. As a matter of fact, dementia is the deterioration of mental and intellectual functions caused by brain diseases in adults when they are mature, which affects the comprehensive performance of life and work ability. Most dementia cases are caused by Alzheimer's disease (AD) and multiple infarct dementia (vascular dementia, multi-infarct dementia). Alzheimer's disease is characterized by atrophy, shedding, and degenerative alterations in brain cells, and its occurrence is linked to age. The fraction of the population with dementia is smaller before the age of 65, and it increases after the age of 65. Since women live longer than men, the proportion of women with Alzheimer's disease is higher. Multiple infarct dementia is caused by a cerebral infarction, which disrupts blood supply in multiple locations and impairs cerebral cortex function. Researchers worldwide are investigating ways to prevent Alzheimer's disease; however, currently, there are no definitive answers for Alzheimer's prevention. Even so, research has shown that we can take steps to reduce the risk of developing it. Prospective studies have found that even light to moderate physical activity can lower the risk of dementia and Alzheimer's disease. Exercise has been proposed as a potential lifestyle intervention to help reduce the occurrence of dementia and Alzheimer's disease. Various workout modes will be introduced based on various physical conditions. In general, frequent exercise for 6-8 weeks lessens the risk of dementia development.
Topics: Alzheimer Disease; Cognition; Cognitive Dysfunction; Exercise; Female; Humans; Male; Prospective Studies
PubMed: 34948942
DOI: 10.3390/ijerph182413331 -
Frontiers in Aging Neuroscience 2021Vascular dementia (VaD) is the second most common form of dementia after Alzheimer's disease (AD); where Alzheimer's accounts for 60-70% of cases of dementia and VaD... (Review)
Review
Vascular dementia (VaD) is the second most common form of dementia after Alzheimer's disease (AD); where Alzheimer's accounts for 60-70% of cases of dementia and VaD accounts for 20% of all dementia cases. VaD is defined as a reduced or lack of blood flow to the brain that causes dementia. VaD is also known occasionally as vascular contributions to cognitive impairment and dementia (VCID) or multi-infarct dementia (MID). VCID is the condition arising from stroke and other vascular brain injuries that cause significant changes to memory, thinking, and behavior, and VaD is the most severe stage while MID is produced by the synergistic effects caused by multiple mini strokes in the brain irrespective of specific location or volume. There are also subtle differences in the presentation of VaD in males and females, but they are often overlooked. Since 1672 when the first case of VaD was reported until now, sex and gender differences have had little to no research done when it comes to the umbrella term of dementia in general. This review summarizes the fundamentals of VaD followed by a focus on the differences between sex and gender when an individual is diagnosed. In addition, we provide critical evidence concerning sex and gender differences with a few of the main risk factors of VaD including pre-existing health conditions and family history, gene variants, aging, hormone fluctuations, and environmental risk factors. Additionally, the pharmaceutical treatments and possible mitigation of risk factors is explored.
PubMed: 34566624
DOI: 10.3389/fnagi.2021.720715 -
Translational Stroke Research Apr 2022Pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha...
Pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3' untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.
Topics: Adult; China; Collagen Type IV; Endothelial Cells; Female; Humans; Leukoencephalopathies; Mutation; Pons; Stroke, Lacunar
PubMed: 34415564
DOI: 10.1007/s12975-021-00926-0