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Neurotherapeutics : the Journal of the... Jul 2008Recent findings indicate that neurovascular dysfunction is an integral part of Alzheimer's disease (AD). Changes in the vascular system of the brain may significantly... (Review)
Review
Recent findings indicate that neurovascular dysfunction is an integral part of Alzheimer's disease (AD). Changes in the vascular system of the brain may significantly contribute to the onset and progression of dementia and to the development of a chronic neurodegenerative process. In contrast to the neurocentric view, which proposes that changes in chronic neurodegenerative disorders, including AD, can be attributed solely to neuronal disorder and neuronal dysfunction, the neurovascular concept proposes that dysfunction of non-neuronal neighboring cells and disintegration of neurovascular unit function may contribute to the pathogenesis of dementias in the elderly population, and understanding these processes will be crucial for the development of new therapeutic approaches to normalize both vascular and neuronal dysfunction. In this review, I discuss briefly the role of vascular factors and vascular disorder in AD, the link between cerebrovascular disorder and AD, the clearance hypothesis for AD, the role of RAGE (receptor for advanced glycation end products) and LRP (low density lipoprotein receptor related protein 1) in maintaining the levels of amyloid beta-peptide (Abeta) in the brain by controlling its transport across the blood-brain barrier (BBB), and the role of impaired vascular remodeling and cerebral blood flow dysregulation in the disease process. The therapeutic strategies based on new targets in the AD neurovascular pathway, such as RAGE and LRP receptors, and on a few selected genes implicated in AD neurovascular dysfunction (e.g., mesenchyme homeobox gene 2 and myocardin) are also discussed.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Blood-Brain Barrier; Cerebrovascular Circulation; Cerebrovascular Disorders; Humans; Low Density Lipoprotein Receptor-Related Protein-1; Models, Biological; Receptor for Advanced Glycation End Products; Receptors, Immunologic
PubMed: 18625452
DOI: 10.1016/j.nurt.2008.05.011 -
Experimental Gerontology Apr 2011Alzheimer's disease (AD) is a progressive chronic disorder and is characterized by β-amyloid plaques and angiopathy, tau pathology, neuronal cell death, and... (Review)
Review
Alzheimer's disease (AD) is a progressive chronic disorder and is characterized by β-amyloid plaques and angiopathy, tau pathology, neuronal cell death, and inflammatory responses. The reasons for this disease are not known. This review proposes the hypothesis that a chronic mild longlasting cerebrovascular dysfunction could initiate a cascade of events leading to AD. It is suggested that (vascular) risk factors (e.g. hypercholesterolemia, type 2 diabetes, hyperhomocysteinemia) causes either damage of the cerebrovascular system including silent strokes or causes dysregulation of beta-amyloid clearance at the blood-brain barrier resulting in increased brain beta-amyloid. A cascade of subsequent downstream events may lead to disturbed metabolic changes, and neuroinflammation and tau pathology. The role of NGF on the cell death of cholinergic neurons is discussed. Additional risk factors (e.g. acidosis, metals) contribute to plaque development.
Topics: Acidosis; Alcoholism; Alzheimer Disease; Amyloid beta-Peptides; Animals; Astrocytes; Cerebrovascular Disorders; Cholinergic Fibers; Humans; Hypercholesterolemia; Hyperglycemia; Hyperhomocysteinemia; Inflammation; Models, Neurological; Nerve Growth Factor; Neurodegenerative Diseases; Oxidative Stress; Risk Factors; Signal Transduction; Stroke; Tauopathies
PubMed: 21112383
DOI: 10.1016/j.exger.2010.11.032 -
Journal of Occupational Health Jul 2019Recently, overwork-related disorders have become a major public health concern in Korea. This study investigated the current trends of working hours, causes of death in... (Review)
Review
OBJECTIVES
Recently, overwork-related disorders have become a major public health concern in Korea. This study investigated the current trends of working hours, causes of death in the working population, and compensation rates.
METHODS
We reviewed the current trends of working hours, cause of death statistics in the working population, industrial accident compensation insurance (IACI) statistics, issues of compensation and prevention of work-related cerebro-cardio vascular diseases (CCVDs), mental disorders, and suicide.
RESULTS
Although weekly working hours and the proportion of long working days have decreased, workers in small companies with fewer than five employees and those in the service sector continue to work long hours. The age standardized mortality due to CCVD and suicide was highest among those with managerial roles. In total, 589 CCVD cases and 104 mental disorder or suicide cases were compensated as occupational diseases in 2017. Between 2016 and 2017, 61% of 59 compensated suicides were related to overwork, specifically: long working hours, increased responsibility, or increased workload. The Korean government has introduced various policies to reduce working hours and to increase compensation approval rate for overwork-related CCVDs. Stakeholders have called for the introduction of independent laws to prevent overwork-related disorders, change organizational culture, and address the blind spots of the IACI Act and Labor Standard Act.
CONCLUSIONS
Prevention and compensation policies have improved working conditions in Korea, but there remains much to be done. This review significantly contributes to the understanding of the overall policies and research to prevent overwork-related disorders in Korea.
Topics: Cardiovascular Diseases; Cerebrovascular Disorders; Health Policy; Humans; Mental Disorders; Occupational Diseases; Occupations; Republic of Korea; Suicide; Work Schedule Tolerance
PubMed: 31025505
DOI: 10.1002/1348-9585.12060 -
International Journal of Molecular... Mar 2020DNA methylation is an epigenetic mechanism by which methyl groups are added to DNA, playing a crucial role in gene expression regulation. The aim of the present study is...
DNA methylation is an epigenetic mechanism by which methyl groups are added to DNA, playing a crucial role in gene expression regulation. The aim of the present study is to compare methylation status of healthy subjects with that of patients with Alzheimer's, Parkinson's or Cerebrovascular diseases. We also analyze methylation status of a transgenic Alzheimer's disease mouse model (3xTg-AD). Our results show that both global methylation ( = 141) and hydroxymethylation ( = 131) levels are reduced in DNA samples from buffy coats of patients with neurodegenerative disorders and age-related cerebrovascular disease. The importance of methylation and hydroxymethylation reduction is stressed by the finding that DNMT3a mRNA levels are also downregulated in buffy coats of patients with Dementia ( = 25). Global methylation is also reduced in brain, liver and serum samples of 3xTg-AD vs. wild type mice, such as DNMT3a mRNA levels that are also decreased in the brain of 3xTg-AD ( = 10). These results suggest that the use of global methylation and hydroxymethylation levels, together with the study of DNMT3a expression, could be useful as a new diagnostic biomarker for these prevalent disorders.
Topics: Animals; Biomarkers; Cerebrovascular Disorders; DNA Methylation; Disease Models, Animal; Disease Susceptibility; Epigenesis, Genetic; Gene Expression Profiling; Gene Expression Regulation; Mice; Mice, Transgenic; Neurocognitive Disorders
PubMed: 32210102
DOI: 10.3390/ijms21062220 -
Journal of Cerebral Blood Flow and... Sep 2018Approximately 15 million individuals suffer a stroke worldwide each year, and stroke results in death or permanent disability in two-thirds of these individuals. Due to...
Approximately 15 million individuals suffer a stroke worldwide each year, and stroke results in death or permanent disability in two-thirds of these individuals. Due to increased knowledge and management of modifiable risk factors, stroke incidence in developed countries is declining, however remains high at just under 1 million patients per year in the United States alone. Further improving management of patients with cerebrovascular disease (CVD) ultimately will require development and clinical adoption of sensitive markers of hemodynamic and metabolic failure, as well as trials that evaluate how to interpret these markers to optimize therapies. Realizing this goal and reducing the complete burden of CVD is dependent on an improved understanding of the pathophysiological processes that underlie CVD in all stages, including sub-clinical disease processes, acute stroke, and post-stroke recovery mechanisms. This document serves as an introduction to the Journal of Cerebral Blood Flow and Metabolism special issue on cerebrovascular diseases, which is comprised of contributions from experts in each of the above stages of CVD, and outlines current standards for patient management and emerging directions that have potential for improving patient care over the next decade.
Topics: Cerebrovascular Disorders; Humans
PubMed: 30160626
DOI: 10.1177/0271678X17739802 -
TheScientificWorldJournal 2014Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD) is the most... (Review)
Review
Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD) is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked.
Topics: Auditory Diseases, Central; Cerebrovascular Disorders; Hallucinations; Health Services Needs and Demand; Humans; Quality of Life
PubMed: 25401133
DOI: 10.1155/2014/261824 -
Journal of Atherosclerosis and... 2014
Topics: Cerebrovascular Disorders; Humans; Hypolipidemic Agents; Japan; Societies, Medical
PubMed: 24335042
DOI: 10.5551/jat.19661 -
Journal of Nuclear Medicine : Official... Apr 2001Structural and functional images of the brain play an important role as powerful adjuncts in the management of an increasing number of neurologic and psychiatric... (Review)
Review
Structural and functional images of the brain play an important role as powerful adjuncts in the management of an increasing number of neurologic and psychiatric diseases. Brain SPECT, in particular, with perfusion agents or with neuroreceptor imaging radiopharmaceuticals, is rapidly becoming a clinical tool in many places. For many neurologic and psychiatric conditions, this imaging modality has been used in diagnosis, prognosis assessment, evaluation of response to therapy, risk stratification, detection of benign or malignant viable tissue, and choice of medical or surgical therapy. The importance of this technique in nuclear medicine today should not be overlooked, particularly in cerebrovascular diseases, dementias, epilepsy, head injury, malignant brain tumors, movement disorders, obsessive-compulsive disorder, Gilles de la Tourette's syndrome, schizophrenia, depression, panic disorder, and drug abuse.
Topics: Brain; Brain Diseases; Brain Injuries; Cerebrovascular Disorders; Dementia; Epilepsy; Humans; Mental Disorders; Tomography, Emission-Computed, Single-Photon
PubMed: 11337551
DOI: No ID Found -
Journal of Alzheimer's Disease : JAD 2018Subcortical small-vessel disease (SSVD) is a disorder well characterized from the clinical, imaging, and neuropathological viewpoints. SSVD is considered the most... (Review)
Review
Subcortical small-vessel disease (SSVD) is a disorder well characterized from the clinical, imaging, and neuropathological viewpoints. SSVD is considered the most prevalent ischemic brain disorder, increasing in frequency with age. Vascular risk factors include hypertension, diabetes, hyperlipidemia, elevated homocysteine, and obstructive sleep apnea. Ischemic white matter lesions are the hallmark of SSVD; other pathological lesions include arteriolosclerosis, dilatation of perivascular spaces, venous collagenosis, cerebral amyloid angiopathy, microbleeds, microinfarcts, lacunes, and large infarcts. The pathogenesis of SSVD is incompletely understood but includes endothelial changes and blood-brain barrier alterations involving metalloproteinases, vascular endothelial growth factors, angiotensin II, mindin/spondin, and the mammalian target of rapamycin pathway. Metabolic and genetic conditions may also play a role but hitherto there are few conclusive studies. Clinical diagnosis of SSVD includes early executive dysfunction manifested by impaired capacity to use complex information, to formulate strategies, and to exercise self-control. In comparison with Alzheimer's disease (AD), patients with SSVD show less pronounced episodic memory deficits. Brain imaging has advanced substantially the diagnostic tools for SSVD. With the exception of cortical microinfarcts, all other lesions are well visualized with MRI. Diagnostic biomarkers that separate AD from SSVD include reduction of cerebrospinal fluid amyloid-β (Aβ)42 and of the ratio Aβ42/Aβ40 often with increased total tau levels. However, better markers of small-vessel function of intracerebral blood vessels are needed. The treatment of SSVD remains unsatisfactory other than control of vascular risk factors. There is an urgent need of finding targets to slow down and potentially halt the progression of this prevalent, but often unrecognized, disorder.
Topics: Animals; Cerebrovascular Disorders; Dementia; Humans
PubMed: 29562536
DOI: 10.3233/JAD-170803 -
Epilepsy & Behavior : E&B Mar 2022To characterize the relationship between functional seizures (FSe), cerebrovascular disease (CVD), and functional stroke.
PURPOSE
To characterize the relationship between functional seizures (FSe), cerebrovascular disease (CVD), and functional stroke.
METHOD
A retrospective case-control study of 189 patients at a single large tertiary medical center. We performed a manual chart review of medical records of patients with FSe or epileptic seizures (ES), who also had ICD code evidence of CVD. The clinical characteristics of FSe, ES, CVD, and functional stroke were recorded. Logistic regression and Welch's t-tests were used to evaluate the differences between the FSe and ES groups.
RESULTS
Cerebrovascular disease was confirmed in 58.7% and 87.6% of patients with FSe or ES through manual chart review. Stroke was significantly more common in patients with ES (76.29%) than FSe (43.48%) (p = 4.07 × 10). However, compared to nonepileptic controls FSe was associated with both CVD (p < 0.0019) and stroke (p < 6.62 × 10). Functional stroke was significantly more common in patients with FSe (39.13%) than patients with ES (4.12%) (p = 4.47 × 10). Compared to patients with ES, patients with FSe were younger (p = 0.00022), more likely to be female (p = 0.00040), and more likely to have comorbid mental health needs including anxiety (p = 1.06 × 10), PTSD or history of trauma (e.g., sexual abuse) (p = 1.06 × 10), and bipolar disorder (p = 0.0011).
CONCLUSION
Our results confirm the initial observation of increased CVD in patients with FSe and further suggest that patients with FSe may be predisposed to developing another functional neurological disorder (FND) (i.e., functional stroke). We speculate that this may be due to shared risk factors and pathophysiological processes that are common to various manifestations of FND.
Topics: Case-Control Studies; Cerebrovascular Disorders; Electroencephalography; Female; Humans; Male; Retrospective Studies; Seizures; Stroke
PubMed: 35123242
DOI: 10.1016/j.yebeh.2022.108582