Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dementia of Alzheimer's type (DAT), together with vascular dementia, is the most important indication for Ginkgo biloba extract (EGb). The therapeutic efficacy of this extract is founded on neuroprotective, metabolic and rheological effects. In addition to these mechanisms--which also form the basis of the activity of the older synthetic nootropics--the hypothesis that DAT is due to a "cholinergic deficit" at central synapses has led, over the last decade, to the development of a new group of drugs for this indication, the cholinesterase (ChE) inhibitors. Thus nowadays, EGb is competing, on the synthetic side, with the ChE inhibitors tacrine, donepezil, rivastigmine and galantamine. No direct comparative trials have been undertaken, but long-term studies lasting 24-56 weeks to demonstrate efficacy have been carried out with both groups of substances in accordance with current EU guidelines. To date, only one psychometric scale has gained general acceptance as the primary criterion of efficacy, namely the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), whose scores range from 0 to 70 (the lower the better). The initial scores of patients in the trials were between 20 and 30; the improvements after 6 months treatment (less those seen with placebo) were about 2 points under Ginkgo extract and 2 to 4 points with the ChE inhibitors. However, the relatively small differences are called into question by the occurrence of drug-specific side effects with the ChE inhibitors. Unlike the treatment with EGb, up to 90% of the patients given the ChE inhibitors developed nausea and vomiting, so there is a suspicion that methodological reasons in the sense of an "unblinding" of the treatment groups caused the apparent superiority in the intensity of the effect. In addition, the benefits of treatment were rapidly reversed after ending administration of ChE inhibitors, which did not occur to the same extent with EGb. Adverse drug reactions are more than 10 times more common with the ChE inhibitors and the treatment costs about five times higher than with EGb. Given the limited therapeutic options for DAT, treatment with EGb still appears to be the method of choice compared to the ChE inhibitors.
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PMID:Ginkgo extract or cholinesterase inhibitors in patients with dementia: what clinical trials and guidelines fail to consider. 1280 48

Fluctuating cognition is evidenced in different forms of dementia and is accompanied by electroencephalographic (EEG) abnormalities. The authors hypothesize that cholinesterase inhibitors are effective mostly in patients with fluctuating cognition. Twenty-three patients affected by mild dementia with similar scores on Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog), and Unified Parkinson's Disease Rating Scale evaluation were classified in a group with fluctuating cognition (n = 11) and a group of nonfluctuators (n = 12). All patients were assigned randomly to the branches of a double-blind crossover study of donepezil (DPZ), a 5 to 10-mg dose, versus vitamin E, a 2000 IU dose, for 30 days. MMSE, ADAS-cog, University of California at Los Angeles Neuropsychiatric Inventory (NPI), quantitative EEG, P3 event-related potentials, choice reaction time variability (CRTV) were assessed at baseline and at the end of treatments. At the end of the crossover study all patients received DPZ for 6 months. The dominant EEG frequency variability, low EEG frequencies amplitude, the P3 latency and jitter, CRTV, and NPI was significantly different in the fluctuating cognition group than the nonfluctuating group at baseline (P < 0.001). Short-term DPZ administration induced a significant increase in MMSE scores, reduction of ADAS-cog and of NPI scores (P < 0.003-0.001), increase of EEG alpha activity and reductions of P3 latency and jitter, dominant frequency variability and CRTV (P < 0.009-0.001) in the fluctuating cognition group, and significant increases of MMSE scores (P = 0.03) and a decrease of P3 jitter and dominant frequency variability (P < 0.034-0.041) in the nonfluctuating group. Short-term DPZ effects differed significantly between fluctuating cognition and nonfluctuating patients (0.001). Significant effects of the 6-month observation were observed only in fluctuating cognition patients. Logistic analysis showed that P3 latency predicts the effect of DPZ (P = 0.04, P < 0.01) in the crossover study, and CRTV predicts the effect at the 6-month follow-up.
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PMID:The effects of a cholinesterase inhibitor are prominent in patients with fluctuating cognition: a part 3 study of the main mechanism of cholinesterase inhibitors in dementia. 1452 Jan 64

The efficacy of a centrally active cholinesterase inhibitor, rivastigmine tartrate (ENA 713), in patients with advanced moderate Alzheimer's disease (AD) was evaluated in a 12-month placebo-controlled study. We aimed to investigate whether there was any evidence for the benefits of rivastigmine in patients with severe disease. These patients were compared with matched controls. In this study, 24 patients with advanced moderate AD received rivastigmine for 12 months. Another 20 patients received placebo. Mean daily doses of rivastigmine in the higher-dose group at 3, 6, 9, and 12 months were 6.1 +/- 1.0, 8.3 +/- 1.2, 8.9 +/- 1.3, and 10.7 +/- 1.6 mg/day, respectively. Cognitive abilities were assessed using the 11-item cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). Forty-five percent of placebo-treated patients declined by at least 4 points on the ADAS-cog. Conversely, only 18.3% of patients treated with rivastigmine declined by 4 or more points. Functional disabilities, as assessed using the Disability Assessment for Dementia Scale, remained significantly superior in rivastigmine-treated patients compared with placebo-treated patients. Patients benefited from high-dose rivastigmine treatment on all outcome measures, including the Mini-Mental State Examination, Progressive Deterioration Scale, as well as the Global Deterioration Scale. Patients receiving rivastigmine for 12 months significantly improved compared with placebo-treated patients (p < 0.001). By 52 weeks, patients originally treated with 6-12 mg/day rivastigmine had a significantly better cognitive function than patients originally treated with placebo. Long-term rivastigmine treatment appeared to be well tolerated in patients with advanced moderate AD and significantly benefits the cognitive and functional symptoms of AD.
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PMID:A 12-month study of the efficacy of rivastigmine in patients with advanced moderate Alzheimer's disease. 1538 47

The efficacy and tolerability of the cholinesterase inhibitor rivastigmine in the treatment of Alzheimer disease (AD) have been demonstrated in several clinical trials, which included patients with a wide range of dementia severities. To investigate the association between severity of disease and treatment response, the combined data from three large randomized, placebo-controlled trials were analyzed. The pooled patient population was stratified into three cohorts showing moderately severe (Mini-Mental State Examination score [MMSE] < or = 15), moderate (MMSE 16-22), and mild (MMSE > or = 22) dementia. In each cohort, the effects of rivastigmine 6 to 12 mg/day versus placebo were evaluated using the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog) and the Progressive Deterioration Scale. Rivastigmine 6 to 12 mg/day maintained ADAS-cog scores at or above placebo levels in all cohorts, while cognitive deterioration with placebo was progressive and severity dependent. Activities of daily living showed statistically significant benefits with rivastigmine across all severity cohorts.
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PMID:Disease stage in Alzheimer disease and treatment effects of rivastigmine. 1549 17

In patients with dementia associated with Parkinson's disease (PD), the efficacy and safety of rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, were previously demonstrated in a 24-week double-blind placebo-controlled trial. Our objective was to determine whether benefits were sustained over the long term. Following the double-blind trial, all patients were permitted to enter an active treatment extension study, during which they received rivastigmine 3-12 mg/day. Standard safety assessments were performed. Efficacy assessments included the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) and other measures of cognition, daily function, neuropsychiatric symptoms, and executive function. Of 433 patients who completed the double-blind trial, 334 entered and 273 completed the active treatment extension. At 48 weeks, the mean ADAS-cog score for the whole group improved by 2 points above baseline. Placebo patients switching to rivastigmine for the active treatment extension experienced a mean cognitive improvement similar to that of the original rivastigmine group during the double-blind trial. The adverse event profile was comparable to that seen in the double-blind trial. Long-term rivastigmine treatment appeared well tolerated and may provide sustained benefits in dementia associated with PD patients who remain on treatment for up to 48 weeks.
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PMID:Long-term benefits of rivastigmine in dementia associated with Parkinson's disease: an active treatment extension study. 1622 10

Previous studies have suggested that statin therapy may be of benefit in treating Alzheimer's disease (AD). We initiated a double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to once-daily atorvastatin calcium (80 mg; two 40 mg tablets) or placebo among individuals with mild-to-moderate AD [Mini-Mental State Examination (MMSE) score of 12-28]. Stable dose use of cholinesterase inhibitors, estrogen and vitamin E was allowed, as was the use of most other medications in the treatment of co-morbidities. We demonstrated that atorvastatin treatment produced significantly (P = 0.003) improved performance on cognition and memory after 6 months of treatment (ADAS-cog) among patients with mild-to-moderate AD. This superior effect persisted at 1 year (P = 0.055). This positive effect on the ADAS-cog performance after 6 months of treatment was more prominent among individuals entering the trial with higher MMSE scores (P = 0.054). Benefit on other clinical measures was identified in the atorvastatin-treated population compared with placebo. Accordingly, atorvastatin therapy may be of benefit in the treatment of mild-to-moderately affected AD patients, but the level of benefit produced may be predicated on earlier treatment. Evidence also suggests that atorvastatin may slow the progression of mild-to-moderate AD, thereby prolonging the quality of an afflicted individual's life.
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PMID:Statin therapy in Alzheimer's disease. 1686 15

We aimed to determine prospectively whether rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, provided benefits in patients with and without visual hallucinations in a population with dementia associated with Parkinson's disease (PDD). This was a 24-week double-blind placebo-controlled study. Primary efficacy measures were the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC). Secondary efficacy measures included activities of daily living, behavioral symptoms, and executive and attentional functions. Patients were stratified according to the presence of visual hallucinations at baseline. The study included 188 visual hallucinators (118 on rivastigmine, 70 on placebo) and 348 nonvisual hallucinators (239 on rivastigmine, 109 on placebo). Rivastigmine provided benefits in both visual hallucinators and nonvisual hallucinators. Absolute responses to rivastigmine on the ADAS-cog were comparable over 6 months, although rivastigmine-placebo differences tended to be larger in visual hallucinators (4.27; P = 0.002) than in nonhallucinators (2.09; P = 0.015). On the ADCS-CGIC, differences between rivastigmine and placebo were 0.5 in visual hallucinators (P = 0.030) and 0.3 in nonhallucinators (P = 0.111). Rivastigmine provided benefits on all secondary efficacy measures, and placebo declines and treatment differences were more marked in visual hallucinators. Adverse events were reported more frequently by rivastigmine-treated patients, although this difference was less marked in visual hallucinators. Visual hallucinations appear to predict more rapid decline and possibly greater therapeutic benefit from rivastigmine treatment in PDD.
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PMID:Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson's disease. 1737 57

There was no long-term clinical study on galantamine in Alzheimer's disease (AD) in the Asian population. The objectives of this study were to evaluate the efficacy of galantamine on cognitive function, daily functioning, behavioural symptoms and its safety in Chinese AD patients. This was a 2-year open-label clinical trial. The inclusion criteria were patients with probable AD by the NINCDS-ADRDA criteria. A historical control group (n = 19) of AD patients with no galantamine or other cholinesterase inhibitor therapy was employed. In the galantamine group, 33 and 32 subjects had completed a 1-year and 2-year follow up, respectively. Within the galantamine group and at a 6-month follow up, the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog score) showed an improvement of 2.9 +/- 1.18 (p = 0.019, paired t-test) but remained the same at 1 and 2 years. The Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) deteriorated by 4.31 +/- 2.06 (p = 0.044, paired t-test) at 6 months but showed no significant decline at 1 and 2 years vs. baseline. The Neuropsychiatric Inventory (NPI) score also showed a significant deterioration of 5 +/- 1.99 (p = 0.017, paired t-test) at 6 months, 8.06 +/- 1.97 (p < 0.001, paired t-test) at 1 year and 7.31 +/- 1.76 at 2 years. Comparison between the two groups showed a statistically significant improvement in the 1-year ADAS-cog score but decline in the NPI score in the galantamine vs. control groups. Adverse effects were commonly mild. In Chinese mild-moderate AD patients, galantamine showed beneficial effects mainly on the cognitive function.
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PMID:A 2-year open-label study of galantamine therapy in Chinese Alzheimer's disease patients in Hong Kong. 1731 6

With the development of long-term disease modifying trials, changes in ADAS-Cog at 18 months will rise certainly many questions. We decided to look in the Real.fr study at the links between changes in cognition, ADAS-Cog and function. A total of 346 Alzheimer's patients with ADAS-cog at entry and at 18 months. were eligible for this analysis. These patients were on average 77.44 years old and 254 (72.36%) were women. The great majority lived at home and about 93% were treated with a cholinesterase inhibitor at baseline. Thirty three patients (9%) had a gain of more than 2 points at the ADAS-cog at 18 months (Group I, improvement); 130 (38%) were considered as stable, the reference group (Group II ) characterized by a stability at the ADAS-cog: decline of 2 points to gain of 2 points, 112 subjects (32%) had a moderate decline between 2 and 7 at the ADAScog (Group III) and finally 71 subjects (21%) had a severe impairment more than seven points at the ADAS-cog. A loss of one Basic ADL is certainly highly relevant, and such a change was found at 18 months in more than half of the subjects, which is not surprising for a long-term evolution in mild to moderate AD. An impairment of more than 7 points at the ADAS-cog was found in 21% of the subjects at 18 months and was associated with loss.
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PMID:Long-term changes in ADAS-cog: what is clinically relevant for disease modifying trials in Alzheimer? 1765 94

Galantamine is a cholinesterase inhibitor and allosteric potentiating ligand modulating presynaptic nicotinic acetylcholine receptors that is used in the treatment of Alzheimer disease (AD). The purpose of this study was to determine if galantamine treatment would result in detectable hippocampal metabolite changes that correlated with changes in cognition, as measured by the Mini-Mental State Examination (MMSE) and the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). Short echo-time proton magnetic resonance (MR) spectra were acquired from within the right hippocampus of ten patients using a 4 Tesla magnetic resonance imaging (MRI) scanner. Spectra were used to quantify absolute metabolite levels for N-acetylaspartate (NAA), glutamate (Glu), choline (Cho), creatine (Cr), and myo-inositol (mI). Patient scans and cognitive tests were performed before and 4 months after beginning galantamine treatment, which consisted of an 8 mg daily dose for the first month and a 16 mg daily dose for the remaining three months. The levels of Glu, Glu/Cr, and Glu/NAA increased after four months of treatment, while there were no changes in MMSE or ADAS-cog scores. Additionally, changes (Delta) in Glu over the four months (DeltaGlu) correlated with DeltaNAA, and Delta(Glu/Cr) correlated with DeltaMMSE scores. Increased Glu and the ratio of Glu to Cr measured by MR spectroscopy after galantamine treatment were associated with increased cognitive performance. The increase in Glu may be related to the action of galantamine as an allosteric potentiating ligand for presynaptic nicotinic acetylcholine receptors, which increases glutamatergic neurotransmission.
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PMID:Increased glutamate in the hippocampus after galantamine treatment for Alzheimer disease. 1983 61


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