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)

The relation between disturbances of cholinergic neurotransmission and delusions (DELs) has not been investigated in degenerative dementias such as dementia with Lewy bodies (DLB). A cohort of dementia patients were assessed with standardized clinical evaluations (including the Columbia University Scale for Psychopathology in Alzheimer's Disease), which were repeated annually until death. DLB was confirmed neuropathologically in 21 patients. Neurochemical evaluation included M1 receptor autoradiography (pirenzepine binding), biochemical measurement of choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) histochemistry in brain regions hypothesized to be involved in the genesis of psychosis. Compared with 11 age-matched controls, CHAT and pirenzepine levels were most extensively reduced in the temporal and parietal neocortex of DLB patients. In Brodmann area 36, DELs were significantly associated with elevated pirenzepine binding (131.0 vs 93.5, t = 2.7), whereas visual hallucinations were associated with significant reductions in ChAT (1.7 vs 2.5, t = 2.5). There were no significant associations with other areas or with cholinesterase. Although DELs and visual hallucinations were both linked with disturbances in cholinergic neurotransmission, the nature of the associations was different. Upregulation of the postsynaptic muscarinic receptor may be central in the genesis of DELs, with important treatment implications.
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PMID:Delusions associated with elevated muscarinic binding in dementia with Lewy bodies. 1111 43

Acetylcholine is a modulatory central nervous system (CNS) neurotransmitter involved in diverse brain processes. Historically, drugs that increase CNS cholinergic transmission have been investigated primarily for relieving cognitive symptoms in Alzheimer"s disease (AD). Emerging from these efforts are recent findings that several cholinesterase-inhibitor agents also have a beneficial effect on selected noncognitive symptoms in AD, such as apathy, psychosis, and purposeless motor behaviors. The broad psychotropic effects of cholinergic agents observed in AD and other degenerative conditions highlight potential symptom-based therapeutic indications for these drugs across a variety of neurologic disorders.
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PMID:Cholinergic therapy for neuropsychiatric symptoms in neurologic disorders. 1112 8

The cholinesterase inhibitors provide the first clearly effective treatments for the cognitive deficits of AD and appear to have a beneficial effect on activities of daily living function and noncognitive behavior. There is increasing support for starting donepezil, rivastigmine, or galantamine early in the disease course and maintaining treatment at least during the early and middle stages of AD. Depressive signs and symptoms complicating AD are treated best with SSRIs. Placebo-controlled trials support the use of citalopram and sertraline in AD complicated by depression. The atypical antipsychotics are the first choice for managing psychosis and disruptive agitation in AD and particularly in the Lewy body variant of AD. Studies suggest that low-dose treatment with risperidone, 1 mg/d, or olanzapine, 5 mg/d, offers the optimal ratio of therapeutic to adverse effects.
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PMID:Alzheimer's disease and related disorders. 1134 85

Dementia with Lewy bodies (DLB) accounts for 15 to 20% of late-onset dementias. The overlap of cognitive symptoms, neuropsychiatric features, parkinsonism and severe sensitivity to antipsychotic drugs raise a number of key management issues. The neurochemical profile of DLB provides a good theoretical rationale for the potential value of cholinesterase inhibitor therapy, which is supported by clinical evidence from a number of case series and one placebo-controlled double-blind trial. It appears that cholinesterase inhibitor treatment is well tolerated and improves fluctuating confusion, cognition and psychotic symptoms; however, the evidence can still only be considered preliminary and a further double-blind study is imperative. Given the high prevalence of severe sensitivity to antipsychotic drugs in patients with DLB, their role in the treatment of psychiatric symptoms and behavioural problems is uncertain, although a small case report literature indicates that some patients may benefit. On the current balance of evidence, prescription of antipsychotic agents to patients with DLB is not recommended, although further studies focussing on patients with severe and intractable neuropsychiatric symptoms are required. Provisional case series indicate a high degree of motor response to levodopa therapy, although controlled trials are a priority to carefully evaluate the benefits in the context of possible adverse effects, such as the exacerbation of psychosis.
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PMID:Dementia with Lewy bodies: clinical features and treatment. 1141 14

Alzheimer's disease (AD) patients exhibit a variety of behavioral alterations including agitation, apathy, depression, anxiety, delusions, irritability and disinhibition. Most patients with AD exhibit neuropsychiatric symptoms, and behavioral changes become more frequent with advancing disease severity. The NPI is a valid and reliable means of assessing neuropsychiatric symptoms in patients with dementia. The NPI correlates with increasing disability in activities of daily living and increasing cognitive impairment. Physical illness contributes little to behavioral symptoms measured by the NPI. Reduced frontal lobe metabolism and perfusion have been identified in patients with apathy, agitation, psychosis and depression. Patients with elevated agitation scores on the NPI have a higher burden of frontal lobe neurofibrillary tangles than patients without agitation. The NPI is sensitive to behavioral improvements following treatment with cholinesterase inhibitors and psychotropic agents. Neuropsychiatric symptom profiles differ among dementia syndromes, and the NPI provides a means of assessing neuropsychiatric symptoms that may aid in differential diagnosis. Evaluation of neuropsychiatric symptoms is a critical aspect of dementia diagnosis and management.
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PMID:Neuropsychiatric assessment of Alzheimer's disease and related dementias. 1144 57

Depression, hallucinations, psychosis and cognitive deficits may often complicate advanced Parkinson's disease. Their detection and treatment have extraordinary importance, as they may cause significant invalidity and even an increase in mortality. Optimization of antiparkinsonian therapy may exert a positive influence on depressive symptoms, and should therefore be performed before antidepressant drugs are started. On the other hand, hallucinations and dementia do usually benefit from a discontinuation or dosage reduction of anticholinergic drugs, selegiline, DA-agonists and amantadine. When a levodopa monotherapy is indicated, slow-release formulations should be avoided. When a neuroleptic treatment is needed, clozapine and maybe quetiapine should be preferred. Preliminary evidence suggests that cholinesterase inhibitors might partially improve cognitive deficits in Parkinson's disease.
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PMID:[Psychological and cognitive problems in Parkinson disease--therapeutic possibilities]. 1193 48

Several studies have reported the efficacy of donepezil (a cholinesterase inhibitor) in patients with Alzheimer's Disease, not only for memory disturbances but also for psychotic and behavioral disturbances. We have experienced one such case that was a 74-year-old female patient with Alzheimer's Disease. Donepezil remarkably improved, for the most part, these symptoms in this case. The scale of Mini-Mental State Examination (MMSE) was improved from 21/30 to 26/30, and the Alzheimer's Disease Assessment Scale (ADAS) was improved from 21.7/70 to 16.3/70. It took about 8 weeks of treatment with donepezil to achieve these results, although some adverse effects associated with the use of donepezil were found in this case. It became difficult for the nursing staff to give care because of hyperactivity and self-assertion.However, the relationship between donepezil and these behavioral disturbances was not clear.This case indicates that donepezil may exacerbate symptoms in Alzheimer's Disease patients who have psychotic and behavioral problems. From a clinical point of view, we concluded that donepezil is therapeutically efficacious for Alzheimer's Disease sufferers, but that some problems still exist.
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PMID:[The efficacy of donepezil in Alzheimer's disease]. 1218 72

Impairments of cortical cholinergic inputs from the nucleus basalis magnocellularis fundamentally alter information processing and attentional function, thereby advancing the severity of psychopathology in major neuropsychiatric disorders. It was previously shown in adult rats that bilateral 192 IgG saporin-induced selective immunolesioning of the cholinergic neurons in the nucleus basalis produces pronounced and long-lasting deficits in sensorimotor gating measured by prepulse inhibition of the startle reflex. This behavioral paradigm is considered a valid model of sensorimotor gating deficits in the psychotic spectrum and efforts to analyze the significance of the cholinergic basal forebrain in this context are of great interest. In the present study the predictive value of the selective cholinergic immunolesioning model was tested by examining the ability of the cholinesterase inhibitor rivastigmine to restore prepulse inhibition in immunolesioned rats. We report here a pronounced restoring effect of acute (0.75 or 1.5 mg/kg s.c.) as well as repeated (0.75 mg/kg s.c. b.i.d., for 10 days) treatment with rivastigmine in this model of disrupted prepulse inhibition. Intra-nucleus basalis magnocellularis infusions of 192 IgG saporin resulted in extensive loss of basal-cortical cholinergic neurons as shown by the marked decrease in basal telencephalic choline acetyltransferase immunopositive neurons and cortical choline acetyltransferase activity. In this condition, rivastigmine was found to significantly increase cortical acetylcholine extracellular levels in lesioned animals measured by in vivo microdialysis. Taken together, our results strengthen the proposal that the nucleus basalis represents a critical station of the startle gating circuitry. In addition, our findings strongly indicate that even after dramatic decrease of cholinergic neurons, inhibition of acetylcholinesterase restores the cholinergic synaptic function to a point approaching normalization of experimentally induced psychopathology.
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PMID:Rivastigmine antagonizes deficits in prepulse inhibition induced by selective immunolesioning of cholinergic neurons in nucleus basalis magnocellularis. 1220 57

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

Behavioral and psychological symptoms of dementia (BPSD) are a common manifestation of Alzheimer's disease (AD) and other dementia syndromes. Patients experience prominent and multiple symptoms, which are both distressing and a source of considerable social, health, and economic cost. Development of symptoms is in part related to progressive neurodegeneration and cholinergic deficiency in brain regions important in the regulation of behavioral and emotional responses including the cortex, hippocampus, and limbic system. Cholinesterase (ChE) inhibitors offer a mechanism-based approach to therapy to enhance endogenous cholinergic neurotransmission. Studies using ChE inhibitors have demonstrated their clear potential to improve or stabilize existing BPSD. Differences have been noted between selective acetylcholinesterase (AChE) inhibitors (donepezil and galantamine) and dual ChE inhibitors (rivastigmine) in terms of treatment response. While donepezil has shown efficacy in moderate to severe noninstitutionalized AD patients, conflicting results have been obtained in mild to moderate patients and in nursing home patients. Galantamine has been shown to delay the onset of BPSD during a five-month study but has been otherwise poorly studied to-date. Both donepezil and galantamine have not as yet demonstrated efficacy in reducing psychotic symptoms or in reducing levels of concomitant psychotropic medication use. Studies with the dual ChE inhibitor rivastigmine in mild to moderately severe AD and in Lewy body dementia (LBD) have shown improvements in behavioral symptoms including psychosis. Improvements have been maintained over a period of up to two years. In addition, institutionalized patients with severe AD have shown symptomatic benefits with a reduction in the requirement for additional psychotropic drugs following treatment with rivastigmine. The psychotropic properties associated with rivastigmine may in part be mediated through effects on butyrylcholinesterase. Current treatment options are limited for patients with dementia syndromes other than AD. However, data concerning rivastigmine in patients with LBD and preliminary studies in Parkinson's disease dementia and vascular dementia suggest a role for ChE inhibitors across the spectrum of dementia syndromes. Finally, studies that incorporated a delayed start design demonstrate that ChE inhibitors may delay the progression of BPSD.
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PMID:The ABC of Alzheimer's disease: behavioral symptoms and their treatment. 1263 79


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