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

---

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

Impairment of attention and memory in patients with Alzheimer's disease (AD) is associated with significantly lower levels of acetylcholine. Inhibition of the breakdown of acetylcholine by blocking the enzymes acetylcholinesterase and butyrylcholinesterase with rivastigmine improves this cholinergic depletion. Thus rivastigmine administration provides established, effective, long-term symptomatic treatment in AD and Parkinson's disease (PD) patients with dementia. A sustained treatment with cholinesterase inhibitors in general may also induce a certain deterioration of fine motor behavior, which may play a crucial role in the treatment of PD patients with dementia. Recent studies show that this altered balance between dopamine and acetylcholine due to cholinesterase inhibition, with its possible negative impact on motion behaviour, does not present a major problem in clinical practice in AD patients and may be compensated for by modification of dopaminergic substitution in PD patients with dementia. However, progression of neurodegeneration increases the vulnerability for psychosis in AD and PD patients with dementia in combination with dehydration and often requires additional application of neuroleptics. Since classical neuroleptics increase extrapyramidal symptoms, atypical neuroleptics are used. Out of these, quetiapine shows a distinct lower anticholinergic (muscarinergic) potency with beneficial effects on cognition. This favors its use in combination with rivastigmine.
...
PMID:Rivastigmine in the treatment of patients with Alzheimer's disease. 1930 May 54

Behavioral and psychological symptoms of dementia (BPSD), i.e. verbal and physical aggression, agitation, psychotic symptoms (hallucinations and delusions), sleep disturbances, oppositional behavior, and wandering, are a common and potentially severe problem complicating dementia. Their prevalence is very high and it is estimated that up to 90% of patients with Alzheimer's disease (AD) may present at least one BPSD. Beside the obvious impact on the quality of life of people with dementia, BPSD are responsible for increased risk of patient institutionalization and increased costs. Furthermore, they are associated with caregivers' stress and depression. Drugs used include antipsychotics, antidepressants, anticonvulsivants, anxiolytics, cholinesterase inhibitors and N-methyl-D-aspartate receptor modulators. Among these, the most commonly used are anti-psychotics. These drugs have been used for many decades, but in the last years new compounds have been marketed with the promise of comparable efficacy but less frequent adverse effects (especially extra-pyramidal side effects). Their safety, however, has been challenged by data showing a potential increase in adverse cerebrovascular side effects and mortality. This review will summarize the pathophysiology and neuropharmacology of BPSD, it will describe the characteristics of the anti-psychotics most commonly used focusing on their efficacy and safety in BPSD.
...
PMID:Antipsychotics for the treatment of behavioral and psychological symptoms of dementia (BPSD). 1930 92

Lewy body dementia (LBD) is a progressive brain disease manifest as dementia and parkinsonism, along with psychotic and autonomic disorders. Although studies in recent years have demonstrated the positive effects of cholinesterase inhibitors in LBD, the search for therapeutic agents with other mechanisms of action remains relevant. An open, controlled, 16-week study was performed with the aim of evaluating the efficacy and safety of memantine in patients with clinically diagnosed LBD (criteria of McKeith et al., 1999). The study included 23 patients (mean age 69.2 +/- 5.9 years), who were divided into two groups: 14 patients received memantine at a dose of 20 mg/day and nine patients constituted the control group. Efficacy was evaluated using a battery of quantitative neurospychological tests, clinical scales for assessment of fluctuations in mental states, scales for assessment of behavioral and psychotic disorders, and the general clinical impression scale. The results demonstrated that memantine had positive effects on the patients' general status and cognitive functions (increases on the mini mental state examination by 1.5 points), mainly because of improvements in attention and control functions. There were also reductions in the severity of fluctuations in mental state, aggressivity, lack of spontaneity, and disinhibition. The severity of psychotic and motor disorders did not change significantly. Tolerance of the agent was good, only two patients withdrawing from the study because of episodes of confusion during the dose titration period.
...
PMID:Efficacy and safety of memantine in Lewy body dementia. 1951 47

Parkinson's disease has now evolved beyond what was considered to be a traditional motor disorder. It is being increasingly recognized that non-motor symptoms such as cognitive impairment, frank dementia, psychosis, depression, autonomic dysfunction and sleep disturbances are just as integral to the disease spectrum. The cholinergic system has been proposed to play a pivotal role in cognitive dysfunction. Based on interpretation of clinical studies in patients with Alzheimer's, cholinesterase inhibitors have also been studied for dementia associated with Parkinson's disease. Most of these include large and small placebo-controlled studies and several pilot studies have indicated that cholinesterase inhibitors have a favorable effect on cognition, psychiatric symptoms and global function in Parkinson's disease dementia. A large randomized placebo-controlled clinical trial showed that rivastigmine had moderate improvement in dementia associated with Parkinson's disease. The magnitude of effects in terms of scores for the cognitive subscale of the Alzheimer's disease assessment scale and Alzheimer's disease cooperative study-clinicians global impression of change were similar to those observed among patients with Alzheimer's disease who were treated with cholinesterase inhibitors. A transdermal patch which gradually releases rivastigmine over the application period is now available for use in mild to moderate dementia associated with Parkinson's disease and Alzheimer's disease.
...
PMID:Rivastigmine in Parkinson's disease dementia. 1961 73

Treatment with cholinesterase inhibitors can cause tolerability-related problems in many patients. To facilitate the titration process, rivastigmine, a novel form of the drug (solution), has been elaborated. An objective of the study was to compare efficacy, safety and tolerability of rivastigmine (exelon) used in conventional capsules and/or solution and to assess adherence to this drug in patients with mild and moderate Alzheimer's disease. A prospective uncontrolled multicenter study included 207 patients: 126 (60,8%) received rivastigmine capsules and 81 (39,2%) - a solution and capsules with flexible doses of titration regime. In the latter group, the mean dose of rivastigmine was 8,5+/-1,1 mg daily to the end of titration period that was significantly differed from the daily dose used for capsules 4,8+/-1,9 mg (p<0,01). The treatment resulted in the significant improvement of the state of cognitive functions on the MMSE (from 18,5+/-3,8 to 21,9+/-4,3 scores), reduction of intensity of psychotic disturbances and positive changes in evaluation of satisfaction with the therapy given by caregivers of these patients (p<0,001). Due to statistically significant correlations (r=0,48; p=0,017) between MMSE scores and the final dose of rivastigmine, it is necessary to achieve the maximum tolerable dose level. Six patients receiving capsules were withdrawn from the study whereas all patients receiving the solution and capsules completed the study. The flexible titration regime and using the solution of rivastigmine allow to achieve better tolerability and higher dose of the drug to the end of titration period.
...
PMID:[Results of the open multicenter prospective study of safety and tolerability of rivastigmine (exelon) in different titration regimes in mild and moderate Alzheimer's disease]. 1967 35

Patients with Parkinson's disease (PD) have a high risk of psychiatric complications, like depressive or psychotic syndromes, dementia and sleep disorders. Although these disorders may even precede the onset of motor symptoms, they are often not recognized and therefore not adequately treated. This article provides a comprehensive overview of the therapeutic options of the most commonly observed psychopathological syndromes in PD. In the case of depressive syndromes medication could be optimized by making use of dopamine agonists that have been proven to have antidepressant properties. In recent studies tricyclic antidepressants showed stronger effects than SSRI. Psychotic symptoms are most often evoked by dopaminergic therapy or are seen in the course of cognitive decline. The therapeutic regimen should be built mainly on L-Dopa medication in the lowest tolerated dose, if required in combinations with COMT-Inhibitors. When antipsychotic medication is indicated, clozapine is the first choice. Quetiapine might also be useful in many patients. Psychotic symptoms in demented patients may respond to cholinesterase-inhibitors, that also delay cognitive decline. Patients with PD require an individually optimized therapeutic regimen not only for motor symptoms, but also for frequently occurring psychiatric syndromes since these strongly influence the patients' and their caregivers' quality of life, are predictors for hospitalization and therefore have great economic importance for health care systems.
...
PMID:[Treatment of mental disorders in patients with Parkinson's disease]. 2042 92

This study examined in detail patterns of cholinesterase inhibitors (ChEIs) and memantine use and explored the relationship between patient characteristics and such use. Patients with probable Alzheimer disease AD (n=201) were recruited from the Predictors Study in 3 academic AD centers and followed from early disease stages for up to 6 years. Random effects logistic regressions were used to examine effects of patient characteristics on ChEIs/memantine use over time. Independent variables included measures of function, cognition, comorbidities, the presence of extrapyramidal signs, psychotic symptoms, age, sex, and patient's living situation at each interval. Control variables included assessment interval, year of study entry, and site. During a 6-year study period, rate of ChEIs use decreased (80.6% to 73.0%) whereas memantine use increased (2.0% to 45.9%). Random effects logistic regression analyses showed that ChEI use was associated with better function, no psychotic symptoms, and younger age. Memantine use was associated with better function, poorer cognition, living at home, later assessment interval, and later year of study entry. Results suggest that high rate of ChEI use and increasing memantine use over time are consistent with current practice guidelines of initiation of ChEIs in mild-to-moderate AD patients and initiation of memantine in moderate-to-severe patients.
...
PMID:Longitudinal medication usage in Alzheimer disease patients. 2062 71

Dementia with Lewy-bodies (DLB) and Parkinson's disease dementia (PDD) are no rare causes of dementia. Both have neuropathologically, clinically, and neurochemically much in common. In the course of both conditions frequently psychotic symptoms occur, often induced by antiparkinsonian medication. Treatment of psychotic features with conventional antipsychotics is not tolerated in many cases. Therefore low-dose clozapine treatment is acknowledged usual practise for psychosis in Parkinson's disease and a case report indicates efficacy for psychosis in DLB, too. All other atypical antipsychotics except risperidone are not licensed for dementia in Germany, but risperidone is contraindicated in DLB due to manufacturer's notice and usually not well tolerated in DLB and Parkinson's disease. Open trials indicate safety for treatment of psychosis in DLB and PDD with quetiapine. Randomized controlled trials indicate, that quetiapine is less effective than clozapine against psychotic symptoms in both conditions, although comparatively safe. Cholinesterase inhibitors, especially rivastigmine, are a therapeutic alternative for treating both psychotic and cognitive symptoms in both conditions. Parkinsonism in DLB-patients responds worse to levodopa compared to patient with Parkinson's disease. Anticholinergic drugs often induce delirium in demented patients and therefore should be avoided. The same problem is associated with dopamine agonists in PDD and DLB. Amantadine, a NMDA-receptor antagonist like memantine, potentially bears the same risk of worsening psychotic symptoms. The following preliminary recommendation for drug treatment of PDD and DLB can be given: Stop all anticholinergic medication and reduce levodopa and other antiparkinsonian medication to the tolerated minimum. Levodopa alone is preferred. Treat with cholinesterase inhibitors to the maximum tolerated dose. If there is no adequate response regarding psychotic symptoms, add quetiapine. If this approach fails, replace quetiapine by low-dose clozapine. If behavioural disturbances are due to depression, anxiety, or irritability, treatment with an antidepressant, preferably citalopram, is an option.
...
PMID:[Drug treatment of dementia with Lewy bodies and Parkinson's disease dementia--common features and differences]. 2142 15

Although diagnosed by characteristic motor features, Parkinson's disease may be preceded, and is frequently accompanied by, a wide range of cognitive and neuropsychiatric features. In addition to the most commonly studied disorders of dementia, depression, and psychosis, other relatively common and clinically significant psychiatric complications include impulse control disorders, anxiety symptoms, disorders of sleep and wakefulness, and apathy. These problems may be underrecognized and are frequently undertreated. The emergent focus on nonmotor aspects of Parkinson's disease over the past quarter of a century is highlighted by a nonlinear increase in the number of articles published devoted to this topic. Although the development of newer antidepressants, atypical antipsychotics, and cholinesterase inhibitors in recent years has had a positive benefit on the management of these troublesome and distressing symptoms, responses are frequently suboptimal, and this remains an area of major unmet therapeutic need.
...
PMID:Parkinson's disease: the quintessential neuropsychiatric disorder. 2162 47

Alzheimer's disease typically presents with two often overlapping syndromes, one cognitive, the other behavioral. The behavioral syndrome is characterized by psychosis, aggression, depression, anxiety, agitation, and other common if less well-defined symptoms subsumed under the umbrella entity "behavioral and psychological symptoms of dementia" (BPSD), itself divided into a number of subsyndromes: psychosis, circadian rhythm (sleepwake) disturbance, depression, anxiety, and agitation, it is BPSD with its impact on care providers that ultimately precipitates the chain of events resulting in long-term institutional care. The treatment challenge involves eliminating unmet medical needs (undiagnosed hip fracture and asymptomatic urinary tract infection or pneumonia). Pharmacologic intervention relies on risperidone and, increasingly cholinesterase inhibitors for the control of psychosis (but with response rates of only 65% at tolerable doses), olanzapine and risperidone for anxiety, and carbamazepine and valproic acid for agitation. However, evidence increasingly favors nonpharmacologic interventions, to the extent that these should now be considered as the foundation of BPSD treatment. Problem behaviors are viewed as meaningful responses to unmet needs in the therapeutic milieu. Because the progression and impact of BPSD varies between patients, interventions must be explored, designed, implemented, and assessed on an individual basis. They include: family support and education, psychotherapy reality orientation, validation therapy, reminiscence and life review, behavioral interventions, therapeutic activities and creative arts therapies, environmental considerations (including restraint-free facilities), behavioral intensive care units, and workplace design and practices that aid the ongoing management of professional caregiver stress.
...
PMID:Behavioral and psychological signs and symptoms of dementia: a practicing psychiatrist's viewpoint. 2203 43


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---