In the treatment of mild to moderate Alzheimer's disease, cholinesterase inhibitors (ChEIs) have shown modest clinical benefits.
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The Deco test appears to be a simple tool to alert the physician to the possibility of an aggressive course of the disease which warrants particular management.
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Reduced TAS, AChE activity and learning performance was observed in old rats. Both rivastigmine and selesiline alone improved performance, although they influenced the biochemical parameters in a different way. The combination of the two drugs did not affect learning performance.
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Reported pediatric exposures to antidementia drugs resulted in minimal morbidity and no mortality. Oral rivastigmine exposures were found to be associated with more symptoms and health care facility evaluations.
Recently, several large randomised controlled trials about the treatments of cognitive impairment or dementia due to Parkinson's disease (CIND-PD or PDD) and dementia with Lewy bodies (DLB) were completed. Here, we systematically reviewed the studies (including the recent reports) to provide updated evidence for the treatments of CIND-PD, PDD and DLB.
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The purpose of this systematic review was to compare the safety and tolerability of the cholinesterase inhibitors (ChEIs) donepezil, rivastigmine and galantamine for treating mild to moderate Alzheimer's disease (AD) patients in routine clinical practice.
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SDZ ENA 713 (rivastigmine) is an acetylcholinesterase inhibitor intended for therapeutic use in Alzheimer's disease. The present study compared the pharmacokinetics of [14C]SDZ ENA 713 after intravenous, oral, and dermal administration to male minipigs, and also examined the effects of dose level and skin abrasion on transdermal absorption.
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We examined by morphological methodology the effect of (S)-N-ethyl-3-[(1-dimethyl-amino)ethyl]-N-methyl-phenylcarbamate hydrogentartrate (ENA-713), an acetylcholinesterase (AChE) inhibitor, on ischemia-induced neuronal death in the gerbil hippocampus due to a 5-min ligation of bilateral common carotid arteries after light ether anesthesia. Pyramidal cells had been decreased to 27% of sham-operated controls and the number of hypertrophic astrocytes expressing glial fibrillary acidic protein (GFAP) markedly increased in the hippocampal CA1 subfield 14 days after ischemia. However, post-ischemic administration of ENA-713 (three times 0.2 mg/kg, i.p.) significantly ameliorated this ischemia-induced decrease in the number of pyramidal cells by 47% of sham-operated controls, furthermore, it reduced the ischemia-induced accumulation of GFAP-positive astrocyte in the CA1 region. Together with previous results showing that ENA-713 protected against the ischemia-induced cholinergic abnormalities in the gerbil brain and improved cholinergic dysfunctions in the senescent rat brain, our present findings suggest that ENA-713 prove to be useful for treatment with senile dementia such as cerebrovascular dementia.
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Both switching strategies were well tolerated. Rates of discontinuation for any reason were similar between the groups. Discontinuations due to adverse events were also similar, and the incidence of gastrointestinal adverse events was low. Apart from Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale scores, at the end of the study, there was no statistically significant change from baseline in cognitive, behavioral, or global outcomes. Over half of the patients preferred rivastigmine transdermal patches to a tablet.
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Alzheimer's drugs are believed to have limited availability and to be unaffordable in low- and middle-income countries compared to high-income countries. The price, availability and affordability of Alzheimer's drugs have not been reported before.
Organogels can be prepared by immobilizing an organic phase into a three-dimensional network coming from the self-assembly of a low molecular weight gelator molecule. In this work, an injectable subcutaneous organogel system based on safflower oil and a modified-tyrosine organogelator was evaluated in vivo for the delivery of rivastigmine, an acetylcholinesterase (AChE) inhibitor used in the treatment of Alzheimer's disease. Different implant formulations were injected and the plasmatic drug concentration was assayed for up to 35 days. In parallel, the inhibition of AChE in different brain sections and the biocompatibility of the implants were monitored. The pharmacokinetic profiles were found to be influenced by the gel composition, injected dose and volume of the implant. The sustained delivery of rivastigmine was accompanied by a significant prolonged inhibition of AChE in the hippocampus, a brain structure involved in memory. The implant induced only a minimal to mild chronic inflammation and fibrosis, which was comparable to poly(D,L-lactide-co-glycolide) in situ-forming implants. These findings suggest that tyrosine-based organogels could represent an alternative approach to current formulations for the sustained delivery of cholinesterase inhibitors.
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One review author (JSB) applied the study selection criteria, assessed the quality of studies and extracted data.
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Trials selected were randomized, double-blind, parallel-group, and unconfounded comparisons of galantamine with placebo for a treatment duration of greater than 4 weeks in subjects with AD.
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We performed a blinded review of T2-WI and FLAIR images in 73 patients fulfilling the radiological part of the NINDS-AIREN criteria (mean age, 71 years; range, 49 to 83 years). This sample was drawn from a large multicenter trial on VaD and was expected to have a high prevalence of thalamic lesions. In a side-by-side review, including T1-weighted images as well, lesions were classified according to presumed underlying pathology.
We reviewed randomized trials of adult ICU patients of interventions hypothesized to reduce delirium burden to determine whether interventions that are more effective at reducing delirium duration are associated with a reduction in short-term mortality.
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A single dose, crossover absolute bioavailability and safety study was conducted with rivastigmine intravenous solution (1 mg) and nasal spray (3.126 mg) in eight healthy elderly individuals, aged 58-75 years.
Overall, the standardised effect size for functional outcome measures was small (d = 0.1-0.4) among included studies. However, effect sizes consistently favoured drug treatment over placebo. For all drugs, pooled standardised effect sizes were consistent in both short (<24 weeks; d = 0.25; 95% CI 0.13, 0.37) and long trials (>or=24 weeks; d = 0.29; 95% CI 0.22, 0.36). The pooled effect size was not significantly affected by parameters such as disease severity, age, gender and drug dose. Adverse events were generally limited to gastrointestinal problems, weight loss and dizziness, all of which were reported in <20% of patients on average.
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Of the new users of anticholinesterases (n = 10088), 47% of those on donepezil, 46% of those on galantamine, and 47% of rivastigmine patients discontinued their initial therapy within 6 months. A total of 32% of patients who ceased therapy reinitiated it during the study period; 28% returned to the same index medication and 4% restarted therapy with a different anticholinesterase. The median treatment duration was: 199 days (95% CI, 182-208) for donepezil patients (n = 6705), 233 days (95% CI, 212-259) for galantamine patients (n = 2898), and 219 days (95% CI, 176-260) for rivastigmine patients (n = 394). Patients in community settings were more likely to discontinue their initial anticholinesterases earlier compared to those living at residential aged care facilities (relative risk, RR=1.21; 95% CI, 1.12, 1.31).
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The central cholinergic system is implicated in cognitive functioning. The dysfunction of this system is expressed in many diseases like Alzheimer's disease, dementia of Lewy body, Parkinson's disease and vascular dementia. In recent animal studies, it was found that selective cholinergic modulation affects visuospatial processes even more than memory function.
We describe the case of a patient with persistent psychosis. Nocturnal visual hallucinations persisted in spite of reduced dopaminergic medication and sequential treatment with atypical antipsychotic medication (quetiapine and clozapine) in combination with an acetylcholinesterase inhibitor (rivastigmine). After dispensing a dopamine enhancing antidepressant (mirtazapine), prescribed to improve sleeping, the psychotic symptoms almost immediately disappeared while Parkinson's symptoms declined.
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The disruption of working memory in the delayed non-matching to position (DNMTP) task by the muscarinic antagonist, scopolamine, is considered to be a model of the spatial working memory deficit in Alzheimer's disease (AD) patients.
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This study provides initial evidence that patients with Alzheimer's disease treated with rivastigmine have a reduced risk of initiating therapy with an antipsychotic drug compared with patients who receive no cholinesterase inhibitor treatment. These findings may imply that rivastigmine use could delay the onset of behavioural symptoms that require treatment with antipsychotic medications.
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Most caregivers of patients with mild to moderate AD preferred the transdermal format of rivastigmine to the oral format. Caregivers also reported overall satisfaction, ease of use, and reduced impact on daily activities for transdermal rivastigmine format, in addition to patient improvement compared to their condition under the previous treatment.
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Cholinesterase inhibitors (ChEI) are currently the mainstream symptomatic treatment of patients with Alzheimer's disease (AD). To this end, the response to the treatment with ChEI is clinically difficult to predict. Several demographic, clinical and biological variables have been proposed as pre-treatment predictors of long-term therapy efficacy. The aim of the study was to confirm our initial observations of the significance of a change in plasma levels of beta-amyloid (Abeta) peptides after initial treat-ment with rivastigmine for predicting clinical response to ChEI.
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Taken together, these studies suggest that ChEIs are efficacious in the treatment of PDD.
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Anxiety is among the most prevalent and costly diseases of the CNS, but its underlying mechanisms are not fully understood. Although attenuated theta rhythms have been observed in human subjects with increased anxiety, no study has been done on the possible physiological link between these two manifestations. We found that the mutant mouse for phospholipase C beta 4 (PLC-beta 4(-/-)) showed attenuated theta rhythm and increased anxiety, presenting the first animal model for the human condition. PLC-beta 4 is abundantly expressed in the medial septum, a region implicated in anxiety behavior. RNA interference-mediated PLC-beta 4 knockdown in the medial septum produced a phenotype similar to that of PLC-beta 4(-/-) mice. Furthermore, increasing cholinergic signaling by administering an acetylcholinesterase inhibitor cured the anomalies in both cholinergic theta rhythm and anxiety behavior observed in PLC-beta 4(-/-) mice. These findings suggest that (1) PLC-beta 4 in the medial septum is involved in controlling cholinergic theta oscillation and (2) cholinergic theta rhythm plays a critical role in suppressing anxiety. We propose that defining the cholinergic theta rhythm profile may provide guidance in subtyping anxiety disorders in humans for more effective diagnosis and treatments.
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To compare the safety and tolerability of switching patients with mild-to-moderate Alzheimer's disease from donepezil to either rivastigmine capsule or transdermal patch.
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To quantify the impact of activities of daily living (ADL) scores on the risk of nursing home placement (NHP) in Alzheimer's disease (AD) patients.
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A meta-analysis of three 6-month, placebo-controlled trials of rivastigmine in mild to moderate AD indicated that rivastigmine 6 to 12 mg/d may improve or prevent disruptive BPSD (P < 0.05 vs placebo). In patients with more advanced AD, 2 open-label studies of up to 12 months' duration found that improvements in BPSD were accompanied by a decrease in the use of psychotropic medications. Rivastigmine demonstrated behavioral benefits in patients with dementia with Lewy bodies (DLB) in a double-blind, placebo-controlled study (P < 0.05). In open-label extension studies, rivastigmine provided sustained effects (up to 2 years) in patients with mild to moderate AD or DLB.