Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular dementia is almost always associated with organic brain lesions due to ischemia, not with arteriosclerosis alone. In Japan, more than 50% of dementia in population older than 65 years are of vascular origin. Vascular dementia occurs with diffuse vascular lesions in the cerebral white matter or circumscribed lesions in particular areas such as the thalamus, anterior limb of the internal capsule, and cingulate gyrus, all of which constitute the ascending activating system or the limbic system. Vascular dementia is clinically characterized by stepwise progression, fluctuating course and predominant deterioration of intelligence with relative preservation of personality. Reversibility, disproportionate impairment of intelligence and personality, and dementia caused by a focal lesion observed in vascular dementia pose problems with regard to the classical concept of dementia. The similarity and difference between remitting dementia and disturbance of consciousness remain to be scrutinized.
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PMID:Vascular dementia. 208 4

Vascular dementia (VD) and Alzheimer's type dementia are two main causes of dementia in the aged. Considering historical backgrounds and ethnic differences, a simplified classification of VD is suggested. First, poststroke dementia of acute onset associated with an infarct that is large enough to impair general cognitive functions, or strategically located. Second, multi-infarct dementia that develops incrementally with increasing numbers of infarcts, and which should be classified as multiple cortical infarct dementia and multiple small infarctor lacunar dementia. Third, vascular dementia of the Binswanger type (VDBT). We compared two types of white matter lesions, periventricular hyperintensity (PVH) and confluent centrum semiovale hyperintensity (CCSH) in lacunar stroke patients with regard to the cerebral blood flow (CBF). In patients with PVH, there was a significant positive correlation between the dementia scores and the CBF in the parietal and temporal areas but not in the frontal area. In CCSH patients, there was a significant positive correlation in the frontal area but not in the parieto-temporal areas. Therefore, dementia in most patients with PVH may not be primarily related to the PVH, but may possibly be due to coexisting Alzheimer's type dementia, and dementia in most CCSH patients may be related to cerebrovascular disease. VDBT is unique clinically in its slowly progressive intellectual deterioration and pathologically in diffuse, confluent, and almost symmetrical white matter lesions. For the pathogenesis of VDBT, our studies suggest that hypertension, short-term variations in blood pressure, and a sustained nighttime elevation of blood pressure promote small vessel disease and cause ischemia of the cerebral white matter that is located in the end-fields of penetrating arteries; this leads to an imparied integrity of the blood-brain barrier and free radical generation, both of which may have important roles in producing diffuse white matter degeneration.
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PMID:[Problems in vascular dementia]. 864 89

This paper reviews aspects of existing knowledge and recent concepts related to the development of vascular dementia which, after Alzheimer's disease, is the most frequent type of dementia. The disorder may result from cerebrovascular disorders, including multi-infarct dementia due to thromboembolic disease, other less common vasculopathies and ischemic brain damage secondary to systemic hypotension. Characteristic clinical features are stepwise cognitive deterioration resulting from repeated strokes and the presence of focal signs and symptoms. The clinical distinction between Alzheimer's disease and vascular dementia may be difficult and strict criteria (NINDS/ AIREN) have recently been adopted as standard guidelines for research studies. Vascular dementia and Alzheimer's disease can co-exist, so-called "mixed dementia", and the presence of cerebrovascular disease may worsen Alzheimer dementia. Indeed, there is often a vascular component in the pathogenesis of dementia. The pathogenesis of vascular dementia is complex. Post-stroke patients are at increased risk; some predisposing or risk factors are the volume, number and site (whether strategic or not) of cerebral injuries, distal field vascular injury with reduced cerebral blood flow, white matter ischemia due to small vessel disease, the co-existence of vascular disease and Alzheimer's dementia, and the presence of cognitive decline prior to stroke. There is increasing evidence of a complex relationship between vascular dementia and Alzheimer's disease. When post-stroke dementia is progressive this may reflect associated Alzheimer's disease either unrecognized or asymptomatic prior to the stroke. The apolipoprotein E4 genotype is a risk factor for ischemic stroke, vascular dementia and Alzheimer dementia. Although dementia is usually irreversible, it is now accepted that cognitive impairment may be delayed, stabilized or sometimes reversed. The treatment of vascular dementia consists of two approaches: preventive measures, including attempts to control risk factors for stroke and the use of antiplatelet agents and/or surgery, and the treatment of cognitive symptoms. Nootropic and vasodilator agents have been reported to improve cognitive impairment from various causes. Ongoing research is attempting to show their specific benefit in vascular dementia.
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PMID:From neuronal and vascular impairment to dementia. 1033 4

Cerebrovascular lesions, mainly lacunes and white matter ischemia, are common in elderly patients with dementia. Vascular dementia (VaD) is the second most common cause of dementia, after Alzheimer's disease (AD). However, lacunar strokes have become an important factor in the clinical expression of AD. Also, population-based studies indicate that vascular risk factors increase the risk of developing AD. It is postulated here that the two main causes of VaD-stroke and ischemic heart disease (IHD)-may be responsible for the majority of cases of dementia in the elderly. STROKE RELATED VaD: Cerebrovascular disease (CVD) is the second leading cause of death worldwide. About 1/3 of stroke survivors [range: 25-41%] 65 years old and above develop VaD within 3 months following the ictus. In the USA alone, 125,000 new cases/year of VaD occur after ischemic stroke (about 1/3 of the 360,000 incident cases of AD). Therefore, more than 1 million elderly people are currently affected by poststroke VaD in the USA. Since current criteria identify "pure" cases of AD and VaD, it is likely that "AD plus CVD" ("mixed" dementia) could be responsible for a large number of cases currently diagnosed as probable AD. CARDIOGENIC VAD: By 2020, IHD leading to congestive heart failure (CHF) will become the leading cause of disability worldwide. Vascular cognitive impairment occurs in 26% of patients discharged from hospitals after treatment for CHF. Cognitive dysfunction correlates with left ventricular dysfunction and systolic blood pressure below 130 mm Hg. CHF is a leading cause of hospital admissions in Western nations (4.5 million cases in the USA alone) and is a growing problem in developing countries. Furthermore, over 800,000 patients/year undergo coronary artery bypass graft (CABG) surgery worldwide, including 300,000 patients in the USA. Measurable cognitive dysfunction occurs post-CABG in 80-90% of patients at hospital discharge. Long-term (5 years) incidence of cognitive defects is 42%. Finally, an international study found short-term postoperative cognitive dysfunction in 26% of patients (>60 years) after abdominal or orthopedic surgery; most of them may be instances of VaD. In conclusion, VaD may be the most underdiagnosed and undertreated form of dementia in the elderly.
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PMID:Vascular dementia may be the most common form of dementia in the elderly. 1241 49

Vascular dementia (VaD) is the second most common type of dementia in the elderly after Alzheimer's disease (AD). Evidence is presented indicating the occurrence of cholinergic dysfunction in VaD, independent from AD. Controlled clinical trials of cholinesterase inhibitors (ChEIs) in VaD and in patients with AD plus cerebrovascular disease are reviewed. Compared with placebo, ChEI treatment improves cognition, behavior, and activities of daily living. Cholinergic deficits in patients with VaD may result from ischemia of basal forebrain cholinergic nuclei that are irrigated by penetrating arteries that are highly susceptible to arterial hypertension, or from ischemic lesions in basal ganglia or white matter that sever the extensive cholinergic cortical projections. Cholinergic stimulation produces increases in cortical cerebral blood flow that may be relevant to the therapeutic effect of ChEIs.
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PMID:Cholinergic dysfunction in vascular dementia. 1571 81

(1) This study was to evaluate the anti-cholinesterase (ChE), cognition enhancing and neuroprotective effects of FS-0311, a bis-huperzine B derivative. (2) ChE activity was evaluated using a spectrophotometric method. Cognitive deficits in mice were induced by scopolamine or transient brain ischemia and reperfusion. Water maze was used to detect the cognitive performance. PC12 cell injury was induced by beta-amyloid 25-35 (Abeta(25-35)), oxygen-glucose deprivation (OGD), or staurosporine treatment. (3) FS-0311 was a potent, highly specific inhibitor of acetylcholinesterase (AChE). FS-0311 bound to AChE in a reversible manner, causing linear mixed-type inhibition. FS-0311 had a high oral bioavailability and a long duration of AChE inhibitory action in vivo. FS-0311 was found to antagonize cognitive deficits induced by scopolamine or transient brain ischemia and reperfusion in a water maze task. FS-0311 possessed the ability to protect PC12 cells against Abeta(25-35) peptide toxicity, OGD insult and staurosporine-induced apoptosis. The neuroprotective effects of FS-0311 appeared to reflect an attenuation of oxidative stress. (4) With the profile of anti-ChE and neuroprotective activities, FS-0311 might be a promising candidate in neurodegenerative diseases, such as Alzheimer's disease and Vascular dementia.
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PMID:Pharmacodynamic study of FS-0311: a novel highly potent, selective acetylcholinesterase inhibitor. 1778 50

Vascular dementia is a common condition for which there are no effective approved pharmacological treatments available. Absence of effective treatments creates a difficult situation for those suffering from the disease, their caregivers, and healthcare providers. This review will address our current understanding of the mechanisms of nerve cell damage due to ischemia and summarize available clinical trial data on several commonly used compounds including memantine, donepezil, galantamine, rivastigmine, nimodipine, hydergine, nicergoline, CDP-choline, folic acid, as well as such nonpharmacological approaches as validation therapy.
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PMID:Vascular dementia: pharmacological treatment approaches and perspectives. 1804 83

Vascular dementia is caused by blockage of blood supply to the brain, which causes ischemia and subsequent lesions primarily in the white matter, a key characteristic of the disease. In this study, we used a chronic cerebral hypoperfusion rat model to show that the regeneration of white matter damaged by hypoperfusion is enhanced by inhibiting phosphodiesterase III. A rat model of chronic cerebral hypoperfusion was prepared by bilateral common carotid artery ligation. Performance at the Morris water-maze task, immunohistochemistry for bromodeoxyuridine, as well as serial neuronal and glial markers were analyzed until 28 days after hypoperfusion. There was a significant increase in the number of oligodendrocyte progenitor cells in the brains of patients with vascular dementia as well as in rats with cerebral hypoperfusion. The oligodendrocyte progenitor cells subsequently underwent cell death and the number of oligodendrocytes decreased. In the rat model, treatment with a phosphodiesterase III inhibitor prevented cell death, markedly increased the mature oligodendrocytes, and promoted restoration of white matter and recovery of cognitive decline. These effects were cancelled by using protein kinase A/C inhibitor in the phosphodiesterase III inhibitor group. The results of our study indicate that the mammalian brain white matter tissue has the capacity to regenerate after ischemic injury.
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PMID:Phosphodiesterase III inhibition promotes differentiation and survival of oligodendrocyte progenitors and enhances regeneration of ischemic white matter lesions in the adult mammalian brain. 1982 32

Vascular dementia (VD), defined as a loss of memory and cognitive function resulting from vascular lesions in the brain, is the second-most-common cause of dementia in the elderly, after Alzheimer's disease. In recent years, research has focused on the pathogenesis of VD, and mitochondrial bioenergetic deficits have been suggested to contribute to VD onset. To further investigate the role of mitochondria in VD, we used a rat model of VD, which involved permanent bilateral occlusion of the common carotid arteries (with a 1-week interval between artery occlusion to avoid an abrupt reduction in cerebral blood flow) leading to chronic cerebral hypoperfusion. Prior to occlusion, male Wistar rats underwent 7 days of Morris water maze training. Only animals that could swim and passed the Morris water maze test were chosen for the study. After 5 days of Morris water maze training, mitochondria from the hippocampi of rats, which were randomly selected from animals that could complete the Morris water maze test, were isolated for functional assessment. Mitochondria isolated from the hippocampi of rats from the ischemia group had decreased pyruvate dehydrogenase protein levels, and increased oxidative stress, as manifested by increased hydrogen peroxide production. The ischemia group mitochondria also exhibited decreased respiration coupled to decreased expression and activity of the electron transport chain complex IV (cytochrome c oxidase). These results indicate that the mitochondrial oxidative metabolism is inhibited in the hippocampi of rats following chronic ischemia-induced VD. As the mitochondrial oxidative metabolism deficits, namely mitochondrial bioenergetic deficits directly affect the functions of neurons, it may contribute to VD onset.
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PMID:Mitochondrial bioenergetic deficits in the hippocampi of rats with chronic ischemia-induced vascular dementia. 2323 58

Vascular dementia (VaD) is a history-laden disease entity that dates back to the 19th century when arteriosclerotic brain atrophy due to hardening of the arteries was perceived as the major cause of senile dementia. Its existence had been overshadowed by the emergence of Alzheimer's disease (AD) in the past century and research on AD dominated the field of dementia. Interest in VaD has been revived in recent years as vascular lesions have been shown to make great contributions to the development of dementia, particularly in the elderly. VaD has now evolved into the concept of vascular cognitive impairment (VCI), which encompasses not only VaD but also AD with cerebrovascular disorder and VCI with no dementia. The concept of VCI is intended to maximize the therapeutic potential in dementia management because the vascular component may be amenable to therapeutic intervention particularly in the early stages of cognitive impairment. Subcortical ischemic vascular dementia (SIVD) is pathologically driven by severe stenosis and the occlusion of small vessels that culminate into white matter ischemia and multiple lacunar infarctions in the subcortical structures. The relatively slow progression of symptoms and clinical manifestations associated with cholinergic deficits often make the differentiation of SIVD from AD difficult. The recent development of in vivo amyloid imaging enabled further pathological breakdown of SIVD into pure SIVD and mixed dementia with subcortical ischemia based on the absence or existence of amyloid pathology in the brain. In this article, the authors reviewed the emerging concepts of VaD/VCI and the clinical manifestations, biomarkers, treatments, and preclinical models of SIVD based on the pathophysiologic mechanisms of the disease.
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PMID:Recent updates on subcortical ischemic vascular dementia. 2474 61


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