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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diagnosis and treatment of vascular dementia (VaD) are particularly challenging because of its multiple causal lesions and the variety of its clinical presentations. Even poststroke dementia cases may be due to preexisting Alzheimer's disease. Diagnostic criteria for clinical trials have been implemented quite recently. Of the vasodilator agents, only the ergoloid mesylates have shown mild benefit. The calcium channel blocker nimodipine appears to be useful in subcortical VaD. Of the nootropic agents, memantine appears to be promising. Pentoxifylline produced significant improvement in multi-infarct VaD. Aspirin, triflusal and Ginkgo biloba extract were associated with some stabilization of dementia progression, perhaps due to their antiplatelet effects. Acetyl-cholinesterase inhibitors appear to be useful in improving memory and activities of daily living in VaD. Results of a large trial of donepezil in VaD should be available soon. Hyperbaric oxygen has been reported to be effective in Binswanger's disease. From the public health perspective, stroke prevention, particularly in atrial fibrillation, and the early and adequate treatment of arterial hypertension clearly decrease the incidence of VaD.
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PMID:Perspectives in the treatment of vascular dementia. 1284 69

Development of dementia depends on genetic susceptibility and on risk factors accessible to primary prevention. Among the latter, vascular risk factors are well defined: prevention of hyperhomocysteinemia, diabetes mellitus, hypercholesterolemia, and, to some extent, of arterial hypertension could avoid the cognitive decline of dementia. Estrogen replacement therapy, antiinflammatory drugs, alcohol, vitamin E and intellectual activities seem efficacious in term of primary prevention. When dementia is present, only vitamin E, selegiline and some antiinflammatory drugs have proved efficacy compared to placebo to slow the cognitive decline. Long-term effects of cholinesterase inhibitors need to be investigated in future trials.
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PMID:[Prevention of dementia: is it possible?]. 1286 24

S. lavandulaefolia Vahl. (Spanish sage) extracts and constituents have demonstrated anticholinesterase, antioxidant, anti-inflammatory, oestrogenic and CNS depressant (sedative) effects all of which are currently relevant to the treatment of Alzheimer's disease (AD). The essential oil inhibits the enzyme acetylcholinesterase (AChE) from human brain tissue and bovine erythrocyte and individual monoterpenoid constituents inhibit AChE with varying degrees of potency. In vivo AChE inhibition of select brain (striatal and hippocampal over cortical) AChE was obtained following oral administration of the essential oil to rats. In a study in healthy volunteers essential oil administration produced significant effects on cognition. In a pilot open-label study involving oral administration of the essential oil to patients with AD, a significant increase in diastolic and systolic blood pressure was observed in two patients, however this may have been due primarily to preexisting hypertension and there were no abnormalities in other vital signs or blood samples during the trial period. Although an open label trial is not free from practice effects or rater-caregiver expectations, statistically significant differences between baseline and 6 weeks treatment were a reduction in neuropsychiatric symptoms and an improvement in attention.
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PMID:Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. 1289 83

This paper reviews treatment strategies of myasthenia gravis (MG) that are currently in use: 1. enhancement of neuromuscular transmission with acetylcholinesterase inhibitors; 2. short-term immunotherapies, including plasma exchange and intravenous immunoglobulin therapy; 3. immunosuppression; 4. surgical thymectomy and thymomectomy. Acetylcholinesterase blockers are still used as the first-line treatment of MG. Although most of patients benefit from these drugs, the improvement is usually incomplete and often wanes after weeks or months of treatment. When clinical symptoms are not adequately controlled by anticholinesterase drugs, immunosuppressive therapy is suggested, but indications for treatment take into account age and clinical symptoms (ocular versus generalised myasthenia). Steroids are the most commonly used and most consistently effective immunosuppressive agents for MG treatment but they also have the highest incidence of potential side effects. The use of azathioprine, for monotherapy in initial immunosuppression treatment of MG is controversial. However, data are available, including a randomised trial, to support the use of azathioprine as an adjunctive drug with corticosteroids. Retrospective analyses of the treatment of MG have shown that cyclosporine is also effective but renal toxicity and hypertension are the major factors limiting its use. Mycophenolate mofetil appeared also to be effective as adjunctive therapy in the treatment of refractory and steroid-dependent MG. Intravenous immunotherapy (IVIg) is recommended as an adjunct in the management of MG exacerbations. According to new publications, there are no pronounced differences in the efficacy of IVIg treatment and plasma exchange. Thymomectomy is beneficial and should be considered for all patients with thymoma-associated MG. However, in cases with non-thymomatous autoimmune MG, thymectomy is recommended only for patients below age 55-60 and within the first 6-12 months of disease duration.
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PMID:[Actual aspects of myasthenia gravis treatment]. 1291 9

Alzheimer's disease patients with hypertension or other vascular risk factors have been shown to receive greater symptomatic benefits than patients with strictly Alzheimer's disease following short-term treatment with rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase. We evaluated the long-term efficacy of rivastigmine in Alzheimer's disease patients with or without hypertension. Subjects in a 26-week placebo-controlled trial of rivastigmine entered an open-label extension study for 104 weeks. Efficacy measures included the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Progressive Deterioration Scale (PDS) and Global Deterioration Scale (GDS). Subjects were stratified by the presence or absence of hypertension at baseline. At 104 weeks, there was a trend for hypertensive patients from the original rivastigmine 6-12 mg/day group (early starters), who received rivastigmine for the full 104 weeks) to have better ADAS-cog scores than the original placebo group (late starters), who received open-label rivastigmine for the last 78 weeks only). Significant treatment differences were observed in the hypertensive subgroup on the PDS and GDS. In non-hypertensive patients, changes from baseline at week 104 were similar in 'early' and 'late' starters of rivastigmine treatment. The additional apparent benefits on disease progression detected in patients with hypertension and Alzheimer's disease may be linked to drug effects on cerebrovascular factors. These findings may have an important influence on the way cholinesterase inhibitors are prescribed.
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PMID:Potential long-term effects of rivastigmine on disease progression may be linked to drug effects on vascular changes in Alzheimer brains. 1468 63

Cardiac parasympathetic activity reduces susceptibility to potentially lethal ventricular arrhythmias in heart failure and ischemic heart disease. This influence is mediated in large part by antagonism of the adverse cardiac effects of sympathetic overactivity ("indirect" parasympathetic activity) in addition to the "direct" effects of muscarinic stimulation. Nitric oxide modulates parasympathetic cardiac signaling in some animal models, but human data are lacking. We have investigated the influence of endogenous nitric oxide on cardiac responses to parasympathetic stimulation in healthy humans. In 18 volunteers, we studied chronotropic and inotropic responses to muscarinic stimulation, both before and after prestimulation with isoproterenol. Cardiac muscarinic stimulation was achieved using an intravenous bolus of the short-acting cholinesterase inhibitor, edrophonium. Responses were assessed during a background infusion of a nitric oxide synthase inhibitor (N(G)-monomethyl-L-arginine [L-NMMA]), placebo (saline), or phenylephrine (vasoconstrictor control) in a single-blind, random order, crossover protocol. L-NMMA did not affect chronotropic responses to edrophonium alone (direct parasympathetic activity). The decrease in heart rate attributable to "indirect" parasympathetic activity (derived by comparison with the effect of edrophonium during concurrent adrenergic stimulation) was substantially attenuated by L-NMMA in comparison to both control infusions. No modification of muscarinic inotropic responses by L-NMMA was apparent in comparison to the vasoconstrictor control. Nitric oxide exerts a powerful facilitating influence on indirect (antiadrenergic) but not direct human cardiac parasympathetic control. Stimulation of the endogenous nitric oxide pathway might enhance parasympathetic protection against the adverse influences of cardiac sympathetic overactivity.
Hypertension 2004 May
PMID:Nitric oxide and cardiac muscarinic control in humans. 1503 54

Significant progress in the field of VaD resulted from publication of the NINIDS-AIREN Diagnostic Criteria for VaD (G.C. Roman, T.K. Tatemichi, T. Erkinjuntti, et al., Vascular dementia (VaD): diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43 (1993) 250-260). Epidemiological studies confirmed the importance of VaD as the second most common cause of dementia in the elderly, representing 15-20% of all cases of dementia. In Europe and North America, Alzheimer's disease (AD) predominates over VaD in a 2:1 ratio; in contrast, in Japan and China VaD accounts for almost 50% of all dementias. Case-control studies have identified risk factors for VaD including ageing, hypertension, diabetes mellitus, hyperlipidemia, recurrent stroke, cardiac disease, smoking, sleep apnea, and more recently, hyperhomocysteinemia, among others. Hypertension treatment may prevent VaD and AD. This finding has enormous importance from the Public Health viewpoint to decrease the future number of patients with dementia in the elderly. Along with advances in the field of VaD came a number of controversies and damaging misconceptions and myths. Myth no. 1--Vascular dementia is a non-entity: The false idea that VaD does not exist is particularly destructive because it creates the perspective that VaD is unworthy of study or research. A condition that either does not exist or represents only a minute proportion of all cases of dementia in the elderly, lacks public health relevance and becomes a low priority for research by funding agencies and industry. In fact, vascular brain lesions are the commonest and most important component of dementia in the elderly. Myth no. 2--Vascular dementia is so difficult to diagnose that only experts can recognize and identify it accurately: VaD does exist and the diagnosis of post-stroke VaD, in particular is straightforward. Most cases fulfill NINDS-AIREN criteria for probable VaD; i.e., (1) there is acute onset of dementia demonstrated by impairment of memory and two other cognitive domains, such as orientation, praxis or executive dysfunction; (2) relevant cerebrovascular lesions are demonstrated by neuroimaging; and (3) a temporal relation between stroke and cognitive loss is evident. In the donepezil trials on VaD, post-stroke dementia represented about 75% of the >1,200 patients enrolled. Myth no. 3--Improvement in clinical trials of cholinergics in VaD is due to underlying AD, not to the vascular lesions. Experimental, clinical and pathological evidence has demonstrated cholinesterase deficits in VaD (independently of any concomitant AD pathology), including low acetylcholine in cerebrospinal fluid, and reduced choline acetyltransferase (ChAT) in the brain.
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PMID:Facts, myths, and controversies in vascular dementia. 1553 19

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

Ischemic or hemorrhagic cerebrovascular disease (CVD) produces injury of brain regions important for executive function, behavior, and memory leading to decline in cognitive functions and vascular dementia (VaD). Cardiovascular disease may cause VaD from hypoperfusion of susceptible brain areas. CVD may worsen degenerative dementias such as Alzheimer disease (AD). Currently, the global diagnostic category for cognitive impairment of vascular origin is vascular cognitive disorder (VCD). VCD ranges from vascular cognitive impairment (VCI) to VaD. The term VCI is limited to cases of cognitive impairment of vascular etiology, without dementia; VCI is equivalent to vascular mild cognitive impairment (MCI). Risk factors for VaD include age, hypertension, diabetes, smoking, cardiovascular disease (coronary heart disease, congestive heart failure, peripheral vascular disease), atrial fibrillation, left ventricular hypertrophy, hyperhomocysteinemia, orthostatic hypotension, cardiac arrhythmias, hyperfibrinogenemia, sleep apnea, infection, and high C-reactive protein. Research on biomarkers revealed increased CSF-NFL levels in VaD, whereas CSF-tau was normal. CSF-TNF-alpha, VEGF, and TGF-beta were increased in both AD and VaD. VaD shows low CSF acetylcholinesterase levels. This condition responds to acetylcholinesterase inhibitors, confirming the central role of cholinergic deficit in its pathogenesis. Evidence strongly suggests that control of vascular risk factors, in particular hypertension, could prevent VaD.
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PMID:Vascular dementia. Advances in nosology, diagnosis, treatment and prevention. 1587 77

Using radiotelemetry to monitor blood pressure and core temperature, studies in our laboratory have shown that a prolonged hypertensive response is elicited in rats exposed to chlorpyrifos, an organophosphate-based insecticide. Chlorpyrifos inhibits acetylcholinesterase activity, resulting in central and peripheral stimulation of central cholinergic pathways involved in blood pressure regulation. The spontaneously hypertensive rat has been shown to be more sensitive to central cholinergic stimulation. Therefore, we hypothesized that these rats would be more susceptible and sustain a greater hypertensive response when exposed to chlorpyrifos. Heart rate, cardiac contractility, core temperature, and blood pressure were monitored by radiotelemetry in SHRs and their Wistar Kyoto (WKY) normotensive controls following exposure to chlorpyrifos (10 mg/kg or 25 mg/kg, orally). Baseline blood pressure of SHRs was approximately 35 mmHg above that of WKYs prior to dosing. SHRs exhibited a greater and more sustained elevation in diastolic, mean and systolic blood pressure following exposure to 25 mg/kg of chlorpyrifos. The rise in blood pressure lasted for approximately 56 hours in SHRs compared to approximately 32 hours in WKYs. Chlorpyrifos also led to a prolonged elevation in daytime heart rate in both strains. There was a transient elevation in cardiac contractility in both strains lasting approximately 7 hr after exposure to chlorpyrifos. The hypothermic response to chlorpyrifos was similar in magnitude and duration for both strains. Plasma cholinesterase activity measured 4 hr after exposure to 25 mg/kg chlorpyrifos was inhibited to approximately 40% of control levels in both strains. Using the SHR strain as a model to study susceptible populations, the data suggest that individuals with a genetic predisposition to hypertension may be more susceptible from exposure to organophosphate-based insecticide, as manifested by an exacerbated hypertensive response.
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PMID:The effects of chlorpyrifos on blood pressure and temperature regulation in spontaneously hypertensive rats. 1591 Apr 16


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