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:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The overall goal of all therapeutic interventions in Alzheimer s disease (AD) is the optimisation of the adaptive functions and quality of life of these patients. The general strategy for the use of pharmacological interventions in the treatment of neuropsychiatric manifestations of AD includes the following: 1) An exhaustive evaluation of the psychiatric symptomatology; 2) Establish a hierachy of the simptoms to treat based on their severity of symptoms and on their impact on the caregiver; 3) The identification of an adequate agent based on the type of symptoms and subject s characteristics; 4) The initial use of low doses with gradual titration, and 5) Changing one drug at a time. Regarding psychotic symptons, the introduction of new agents (e.g., risperidone) has replaced the use of traditional treatments (e.g., thioridazine) in patients with AD. The presence of psychomotor agitation and aggression can be treated with great variety of drugs, such as antipsychotics, anticonvulsants, antidepressants, and sedatives. Selective serotonine re uptake inhibitors are the treatment of choice for depressive symptomatology. The cholinesterase inhibitors have shown to be useful in the treatment of hallucinations, anxiety and apathy.
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PMID:[Treatment of neuropsychiatric symptoms in Alzheimer's disease]. 1243 83

Alzheimer's disease is the most frequent form of dementia, where behavioral and cognitive disruption symptoms coexist. Depression, apathy, anxiety, and other conduct disorders are the complaints most often reported by caregivers. Fifty subjects were referred to our Institute with a diagnosis of probable Alzheimer's disease. Cognitive impairment was equally distributed among the subjects. Patients, aged 68 to 76 years old, were randomized to receive inhibitors of cholinesterase (Donepezil, 5 mg/day) alone, or inhibitors of cholinesterase plus selective serotonin reuptake inhibitors (SSRIs) (citalopram HBr, 20 mg/day). We followed up all the patients for one year, with particular concern for neuropsychological aspects associated with eventual behavioral changes. Results indicate that SSRI intake seems to be effective for depression, decreasing it and improving quality of life for both patients and caregivers. Side effects in both groups were few, and there were no study withdrawals. This paper discusses the relationship between dementia and depression, and presents our finding that depressive symptoms, if specifically treated, tend to reduce caregiver stress and improve well-being in patients with Alzheimer's disease.
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PMID:Depression and Alzheimer's disease: symptom or comorbidity? 1250 80

Dementia in Parkinson's disease (PDD) is a frequent and distressing complication with major consequences. Clinical and pathological features closely link PDD and dementia with Lewy bodies (DLB), suggesting they represent part of the same disease spectrum. Although dopaminergic deficiency primarily determines the akinetic-rigid symptoms of PDD and DLB, there is overwhelming evidence that cholinergic dysfunction underpins many of the cognitive impairments and psychotic features. Open-label studies have suggested that cholinesterase inhibitor drugs may exert positive effects upon all aspects of the neuropsychiatric syndrome in PDD and DLB but particularly apathy, anxiety, impaired attention, hallucinations, delusions, sleep disturbance, and cognitive test performance. Worsening of extrapyramidal motor features is reported only rarely. Initial double-blind, placebo-controlled studies in PDD and DLB have so far confirmed these encouraging results. Early identification of PD patients at greatest risk of developing dementia would permit early use of disease modifying treatments which represent the "golden fleece" management approach to these groups.
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PMID:Current treatment of dementia with Lewy bodies and dementia associated with Parkinson's disease. 1450 59

Apathy, a syndrome of decreased initiation and motivation, affects over 70% of individuals with Alzheimer's disease (AD) and is the most common neuropsychiatric symptom reported in AD patients. The syndrome of apathy is associated with functional impairment among patients and elevated stress among their caregivers. Apathy is one of the primary neuropsychiatric manifestations of frontal system dysfunction, and AD-related apathy is thought to reflect the interaction between cholinergic deficiency and neuropathological changes in frontal brain regions. This article reviews the assessment and treatment of apathy in AD, with emphasis on the utility of acetylcholinesterase inhibitors for reducing apathy in AD. The potential benefits of other pharmacologic agents and combined pharmacologic-behavioral interventions are also discussed, and recommendations for future research are provided.
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PMID:Treating apathy in Alzheimer's disease. 1456 28

Observations on the neurochemistry of dementia with Lewy bodies (DLB) have suggested that cholinesterase inhibitors (ChEIs) might be beneficial in treating some clinical symptoms of DLB. A 24-week, multicenter open-label study was designed to assess the safety and efficacy of the ChEI galantamine in patients with DLB, and an interim analysis of results was performed at 12 weeks. Efficacy analyses were performed on data from 25 patients. Scores on the Neuropsychiatric Inventory (NPI-12) improved (decreased) by 7.52 points over the 12 weeks (marginally significant, p = 0.061). NPI-12 scores decreased by half in 12 of the 25 patients. Highly significant improvement was observed in scores on the NPI-4 subscale (delusions, hallucinations, apathy, and depression: p = 0.003). Scores on the Clinician's Global Impression of Change (CGIC) improved by 0.95 points (significant, p = 0.02). Improvements also were found in secondary efficacy variables, including cognitive, functional, activities of daily living, sleep and confusion assessments. Motor scores, as measured by the UPDRS motor subscale, showed mild improvement, which demonstrates that galantamine has no adverse effect on parkinsonian symptoms. Adverse events generally were transient and of mild-to-moderate intensity. Two of the 25 patients discontinued galantamine because of nausea and anorexia. One serious adverse event was recorded, but it was judged to be unrelated to the study medication.
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PMID:Efficacy and safety of galantamine in patients with dementia with Lewy bodies: a 12-week interim analysis. 1467 68

In patients with Parkinson's disease (PD) disturbances of mental state constitute some of the most difficult treatment challenges of advanced disease, often limiting effective treatment of motor symptoms and leading to increased disability and poor quality of life. This article provides an update on the current knowledge of these complications and the use of old and new drugs in their management. Mental state alterations in PD include depression, anxiety, cognitive impairment, apathy, and treatment-related psychiatric symptoms. The latter range from vivid dreams and hallucinations to delusions, manic symptoms, hypersexuality, dopamine dysregulation syndrome and delirium. While some of these symptoms may be alleviated by anti-parkinsonian medication, especially if they are off-period related, treatment-related phenomena are usually exacerbated by increasing the number or dosage of antiparkinsonian drugs. Elimination of exacerbating factors and simplification of drug regimes are the first and most important steps in improvement of such symptoms. However, the advent of atypical antipsychotics such as clozapine has dramatically helped the management of treatment-related psychiatric complications in PD. In patients with dementia associated with PD cognitive functioning and behavioural problems appear to respond to cholinesterase inhibitors, such as rivastigmine or donepezil. Depression is a common problem in early as well as advanced PD, and selective serotonin reuptake inhibitors, reboxetine, and tricyclic antidepressants have been reported to be effective and well tolerated antidepressants. Randomised, controlled studies are required to assess the differential efficacy and tolerability of antidepressants in patients with PD, including the newer antidepressants with serotonergic and noradrenergic properties.
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PMID:Psychiatric aspects of Parkinson's disease--an update. 1525 80

Alzheimer's disease is a neurodegenerative disorder associated with a decline in cognitive abilities. Patients also frequently have noncognitive symptoms, such as anxiety, depression, apathy, and psychosis, that impair daily living. The most commonly prescribed treatments for Alzheimer's disease are acetylcholinesterase inhibitors, such as donepezil and galantamine. Enhanced cholinergic functions caused by these compounds are believed to underlie improvements in learning, memory, and attention. The noncognitive aspects of dementia, however, are usually linked to serotonin and dopamine rather than acetylcholine because those neurotransmitter systems most directly influence mood, emotional balance, and psychosis. Fast-scan cyclic voltammetry applied to mouse striatal brain slices was used to measure the real-time release of dopamine arising from spontaneous activity or from single electrical stimulations. At concentrations that include their prescribed dosage ranges, donepezil (1-1000 nM) and galantamine (50-1000 nM) increase action potential-dependent dopamine release. Consistent with previous literature, the data support slightly different modes of action for donepezil and galantamine. The ability of these commonly prescribed drugs to alter catecholamine release may underlie their influence over noncognitive symptoms of dementia. Furthermore, these results suggest that acting via nicotinic receptors, these drugs may serve presently untapped therapeutic roles by altering dopamine release in other disorders involving dopaminergic systems.
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PMID:Cholinergic drugs for Alzheimer's disease enhance in vitro dopamine release. 1532 45

Donepezil is a selective acetylcholinesterase inhibitor approved for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). Since behavioral symptoms severely affect quality of life for AD patients and their caregivers, predicting behavioral responses to donepezil will be useful in managing patients with AD. In this study, we analyzed 70 consecutive cases with mild to moderate AD. Caregivers were interviewed with the Neuropsychiatric Inventory for behavioral assessment and 4-point improvement at week 12 was accepted as a treatment response. Twenty-one (30.0%) patients showed a behavioral response, while 42 (60.0%) showed no behavioral change and 7 (10.0%) worsened. Dysphoria, anxiety and apathy significantly improved after treatment among the responder group. The baseline profile including age, sex, Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale (ADAS-cog) and the Geriatric Depression Scale did not differ significantly among the three groups. Statistical Parametric Mapping analysis of single photon emission computed tomography (SPECT) images at baseline showed that cerebral blood flow in the premotor and parietotemporal cortices was significantly higher in the responder group than in the worse group. The present study suggested usefulness of SPECT imaging in the prediction of behavioral response to donepezil among AD patients even with similar psychiatric symptoms and cognitive functions.
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PMID:Prediction of psychiatric response to donepezil in patients with mild to moderate Alzheimer's disease. 1546 97

This randomized study evaluated the combined effect of a cognitive-communication program plus an acetylcholinesterase inhibitor (donepezil; donepezil-plus-stimulation group; n = 26), as compared with donepezil alone (donepezil-only group; n = 28) in 54 patients with mild to moderate Alzheimer's disease (AD; Mini-Mental Status Examination score of 12- 28) ranging in age from 54 to 91 years. It was hypothesized that cognitive-communication stimulation in combination with donepezil would positively affect the following: (a) relevance of discourse, (b) performance of functional abilities, (c) emotional symptoms, (d) quality of life, and (e) overall global function, as measured by caregiver and participant report and standardized measures. Cognitive-communication, neuropsychiatric, functional performance, and quality of life evaluations were conducted at baseline and Month 4, the month after the 2-month active stimulation period. Follow-up evaluations were performed at Months 8 and 12. The stimulation program consisted of 12 hr of intervention over an 8-week period and involved participant-led discussions requiring homework, interactive sessions about AD, and discussions using salient life stories. Additive effects of active stimulation with donepezil were examined in 2 ways: (1) comparing mean group performance over time and (2) evaluating change scores from baseline. A Group x Time interaction was found for the donepezil-plus-stimulation group in the emotional symptoms of apathy and irritability as compared with the donepezil-only group. Evaluation of change scores from baseline to 12 months revealed a positive effect for the donepezil-plus-stimulation group on discourse and functional abilities with a trend on apathy, irritability, and patient-reported quality of life. In sum, the research revealed benefits to the donepezil-plus-stimulation group in the areas of discourse abilities, functional abilities, emotional symptoms, and overall global performance. This study adds to growing evidence that active cognitive stimulation may slow the rate of verbal and functional decline and decrease negative emotional symptoms in AD when combined with acetylcholinesterase inhibitors, indicating a need to advance research in the area of cognitive treatments. The fact that AD is a progressive brain disease should not preclude ameliorative treatment.
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PMID:Effects of cognitive-communication stimulation for Alzheimer's disease patients treated with donepezil. 1560 68

Motivation is a concept largely studied by modern psychology and mainly applied in the fields of learning at school, performance at work, competition in sport. Recently neuropsychiatry put forward the syndrome of apathy, a major disorder of the motivation which appears as frequently observed in several neurodegenerative disorders and in particular in Alzheimer's disease. The question raised in the present review is to detect and gather the data which would prove the existence of a physiology and a neurobiology of the motivation, a real prerequisite for any pharmacological project. Precisely, frontal lobe and cingular cortex appear as critical in the activation of motivational process. Acetylcholine and dopamine, at the present time, are considered as the main neurotransmitters involved in such anatomical circuits explaining that pharmacology focuses its interest on acetylcholinesterase inhibitors and dopamine agonists. Studies specifically devoted to motivation and apathy are anxiously expected and should be based on the most recent acquisitions of the neurophilosophy.
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PMID:[Biology of motivation]. 1568 30


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