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)

Neuropsychiatric symptoms seen in Alzheimer's disease (AD) are not simply a consequence of neurodegeneration, but probably result from differential neurotransmitter alterations, which some patients are more at risk of than others. Therefore, the hypothesis of this study is that an imbalance between the cholinergic and serotonergic systems is related to cognitive symptoms and psychological syndromes of dementia (BPSD) in patients with AD. Cholinergic and serotonergic functions were assessed in post-mortem frontal and temporal cortex from 22 AD patients who had been prospectively assessed with the Mini-Mental State examination (MMSE) for cognitive impairment and with the Present Behavioral Examination (PBE) for BPSD including aggressive behavior, overactivity, depression and psychosis. Not only cholinergic deficits, but also the cholinacetyltransferase/serotonin ratio significantly correlated with final MMSE score both in frontal and temporal cortex. In addition, decreases in cholinergic function correlated with the aggressive behavior factor, supporting a dual role for the cholinergic system in cognitive and non-cognitive disturbances associated to AD. The serotonergic system showed a significant correlation with overactivity and psychosis. The ratio of serotonin to acetylcholinesterase levels was also correlated with the psychotic factor at least in women. It is concluded that an imbalance between cholinergic-serotonergic systems may be responsible for the cognitive impairment associated to AD. Moreover, the major findings of this study are the relationships between neurochemical markers of both cholinergic and serotonergic systems and non-cognitive behavioral disturbances in patients with dementia.
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PMID:Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer's disease. 1570 19

Behavioural symptoms such as anxiety, depression and psychosis are common in Parkinson's disease (PD), and dementia occurs in about 90% of the patients. These symptoms can be more disabling than the motor dysfunction and they negatively impact quality of life, increase caregiver distress and are more frequently associated with nursing home placement. Depression can be treated with counselling and pharmacotherapy. Tricyclic antidepressants or selective serotonin reuptake inhibitors are widely used, but there is still need for controlled clinical trials. Management of psychosis in PD is complex and includes elimination of identifiable risk factors, reduction of polypharmacy and administration of atypical neuroleptics, which can alleviate psychotic symptoms without worsening motor functions. Clozapine is the best documented atypical neuroleptic shown to be effective against psychosis in PD patients. Cholinesterase inhibitors may prove additional benefit in psychotic PD patients. Recent evidence from small double-blind and open-label trials suggests that cholinesterase inhibitors may be effective in the treatment of dementia associated with PD.
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PMID:Treatment of behavioural symptoms and dementia in Parkinson's disease. 1581 Aug 93

Cognitive decline and dementia affect approximately 30% to 40% of patients with idiopathic Parkinson's disease during the course of their illness. PD-dementia (PDD) and dementia with Lewy bodies (DLB) are second to Alzheimer's disease in causing degenerative dementia in the elderly. The nosological distinction of the conditions has remained controversial because of broad clinical and pathological overlap. Treatment issues in both clinical settings are virtually identical. Treatment of Parkinsonism is often complicated by drug-induced psychosis and reduced levodopa responsiveness. Cognition, alertness, attention, as well as apathy or aggressive behavior have been shown to respond to treatment with cholinesterase inhibitors in randomized controlled trials both in DLB and PDD. Such treatment may also improve hallucinosis, but many patients will require add-on treatment with atypical neuroleptics to control drug-induced psychotic reactions. Clozapine and quetiapine are the drugs most commonly used and, contrary to classic neuroleptics, risperidone or olanzapine do not seem to cause severe side effects according to published data.
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PMID:Treatment of dementia with Lewy bodies and Parkinson's disease dementia. 1609 95

The neuropsychiatry of Parkinson's disease (PD) and its correlates are reviewed. Dementia occurs in up to 30% and can be treated with cholinesterase inhibitors. Cognitive impairments involve executive, visuospatial, attentional, and memory dysfunctions. Apathy may respond to dopamine agonists or cholines-terase inhibitors. Cognitive impairment, psychosis, and depression predict quality of life. Visual hallucinations and paranoia are common, and respond to low dose clozapine. Depression is common and predicts caregiver burden and depression. The best data suggest the efficacy of nortriptyline and the safety of SSRIs. Anxiety disorders occur in 40% of patients, especially off-period panic attacks and specific phobias. Bromazepam has proven useful for anxiety in PD, but buspirone has only diminished drug-induced dyskinesias to date. Sleep disorders occur in up to 94% of patients. Insomnia is common and is treated by dopaminergic agent dose reduction, nocturnal dosing, treatment of depression, or use of short half-lived hypnotics, depending on etiology. Parasomnias include REM behavior disorder and vivid dreams and nightmares. Excessive daytime somnolence occurs in at least 15% of patients. Sleep attacks are common and patients should be warned about driving when taking dopamine agonists. Sexual disorders occur in most patients. Paraphilias are associated with dopamine agonists, and clozapine may be useful in their treatment. Surgical therapies are associated with a wide variety of neuropsychiatric features, and vigilance for suicide attempts with subthalamic nucleus stimulation seems warranted. Neuropsychiatric disorders are important determinants of quality of life and caregiver burden in PD. More clinical research is needed to establish effective treatments.
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PMID:The neuropsychiatry of Parkinson's disease. 1617 59

Reminyl (galantamine)-- a cholinesterase inhibiting component--was used in treatment of 15 patients with dementia featured by the presence of Levi bodies in brain neurons. The treatment duration was 16 weeks with elevation of the drug dosage every 4 weeks--from 8mg to 12 mg twice a day. Treatment evaluation was conducted clinically and by psychometrical tests and scales. Reminyl improved patient's state reducing cognitive, behavioral and psychotic disturbances. The highest effect was achieved in 2/3 patients. Side-effects (nausea, dizziness, dyspepsia, general sickness, etc) were observed in 47% cases. Only in 2 patients they caused treatment withdrawal. The absence of aggravation of extrapyramidal disorders is emphasized.
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PMID:[Reminyl efficacy in dementia with Levi bodies]. 1628 74

Dementia with Lewy bodies (DLB) is known for its partial resistance and hypersensitivity to some treatments, but DLB is treatable with cholinesterase inhibitors, sometimes better than in Alzheimer's disease. Cholinesterase inhibitors have a symptomatic effect on cognition and behavior. Nevertheless, new antipsychotics are sometimes also useful to manage psychotic symptoms. Although DLB patients respond less well to levodopa than patients with Parkinson's disease, 75 percent of DLB patients improve with levodopa, which is the best-tolerated dopaminergic agent. Nonpharmacological strategies include speech therapy, physiotherapy, psychotherapy, and educational support groups for care givers.
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PMID:[Treatment of dementia with Lewy bodies]. 1644 31

Psychosis may pose a greater challenge than cognitive decline for patients with dementia and their caregivers. The nature and frequency of psychotic symptoms varies over the course of illness, but in most patients, these symptoms occur more often in the later stages of disease. Management of psychosis requires a comprehensive nonpharmacologic and pharmacologic approach, including an accurate assessment of symptoms, awareness of the environment in which they occur, and identification of precipitants and how they affect patients and their caregivers. Nonpharmacologic interventions include counseling the caregiver about the nonintentional nature of the psychotic features and offering coping strategies. Approaches for the patient involve behavior modification; appropriate use of sensory intervention; environmental safety; and maintenance of routines such as providing meals, exercise, and sleep on a consistent basis. Pharmacologic treatments should be governed by a "start low, go slow" philosophy; a monosequential approach is recommended, in which a single agent is titrated until the targeted behavior is reduced, side effects become intolerable, or the maximal dosage is achieved. Atypical antipsychotics have the greatest effectiveness and are best tolerated. Second-line medications include typical antipsychotics for short-term therapy; and, less often, anticonvulsants, acetylcholinesterase inhibitors, antidepressants, and anxiolytics. Goals of treatment should include symptom reduction and preservation of quality of life.
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PMID:Behavior disorders of dementia: recognition and treatment. 1650 7

Although available treatments for Huntington's disease (HD) are imperfect, thoughtful application can positively impact quality of life. Dopamine antagonists can provide control of the troublesome hyperkinetic movements. These agents can also diminish the frequency of hallucinations and delusions when symptoms of psychosis occur. Classical neuroleptics have the widest utilization, although atypical antipsychotics are being increasingly used. Suppression of choreiform movements has also been reported with amantadine and tetrabenazine, which is not currently approved in the United States but under investigation. Alteration in mood can be successfully managed with a variety of antidepressant medications. Superior tolerability and value in the management of a variety of behavioral disturbances have lead to extensive use of serotonin reuptake inhibitors. Modest disturbance of mood can sometimes be addressed with anticonvulsant medications. Considered a manifestation of advanced disease, dementia is less commonly addressed therapeutically. However, gathering experience suggests improved cognitive function can occur with cholinesterase inhibitor therapy. Frequently overlooked is the value of rehabilitation services in the management of diverse symptoms. Although the value of a dysphagia evaluation is apparent, the benefit to be derived from physical and occupational therapy involvement cannot be overstated. Current therapeutic trials will undoubtedly provide additional therapies to moderate symptoms, but once the mechanism(s) of selective striatal projection neuron degeneration are delineated, a revolution in the management of HD will occur.
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PMID:Huntington's Disease. 1656 82

The practice guideline 'Diagnosis and pharmaceutical treatment of dementia' emphasizes that a nosological diagnosis should be made and that it is important to assess the extent of need for care. The guideline recommends the use of diagnostic criteria for the various conditions that can cause dementia. With respect to ancillary investigations, the burden to the patient should be weighed against the benefits of increasing diagnostic confidence. Observation of the course of the disease, laboratory and cerebrospinal-fluid investigations, neuropsychological and EEG examinations, and neuroimaging all increase diagnostic confidence. Treatment with a cholinesterase inhibitor or memantine should always be embedded in a comprehensive-treatment protocol that includes explicit discussion of treatment goals and expectations at baseline, in combination with criteria for starting and stopping treatment. Guidelines for evaluating the effects of treatment with cholinesterase inhibitors or memantine are specified. If psychosis, depression or behavioural disturbances occur in patients with dementia, antidepressants, antipsychotics or anticonvulsants may be indicated.
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PMID:[The practice guideline 'Diagnosis and pharmaceutical treatment of dementia']. 1692 52

Parkinson's disease is a neurodegenerative disorder causing not only motor dysfunction but also cognitive, psychiatric, autonomic and sensory disturbances. Symptoms of dementia and psychosis are common: longitudinal studies suggest that up to 75% of patients with Parkinson's disease may eventually develop dementia, and the prevalence of hallucinations ranges from 16-17% in population-based surveys to 30-40% in hospital-based series. These cognitive and behavioural features are important in terms of prognosis, nursing home placement and mortality. The pattern of cognitive deficits in Parkinson's disease is variable, but often includes executive impairment similar to that seen in patients with frontal lesions, as well as episodic memory impairment, visuospatial dysfunction and impaired verbal fluency. The most common manifestation of psychosis in Parkinson's disease is visual hallucinations, but delusions, paranoid beliefs, agitation and florid psychosis can also occur. An understanding of the pathophysiology underlying these symptoms is essential to the development of targeted therapeutic strategies. Post-mortem studies suggest an association between Lewy body deposition and dementia in Parkinson's disease, and indeed Parkinson's disease and dementia with Lewy bodies may form part of the same disease spectrum. Whether Lewy bodies actually play a causative role in cognitive dysfunction, however, is unknown. Deficits in neurotransmitter systems provide more obvious therapeutic targets and dysfunction of dopaminergic, cholinergic, noradrenergic and serotonergic systems have all been implicated; these may each underlie different features of Parkinson's disease dementia, perhaps explaining some of the heterogeneity of the syndrome. Psychosis has traditionally been considered as a dopaminergic drug-induced phenomenon, but factors intrinsic to the disease process itself also cause hallucinations and delusions. These factors may include Lewy body deposition in the limbic system, cholinergic deficits and impairments of primary visual processing. Therapeutic intervention for cognitive and behavioural symptoms in Parkinson's disease currently focuses on two main groups of drugs: cholinesterase inhibitors and atypical antipsychotics. A recent large, randomised, controlled trial suggests that cholinesterase inhibitors can produce a modest improvement in cognitive function, as well as psychotic symptoms, generally without an adverse effect on motor function. Certain atypical antipsychotics allow hallucinations, delusions and behavioural problems to be brought under control with minimal deleterious effects on motor function and cognition, but their safety in elderly patients has recently been called into question. Deep brain stimulation does not appear to be a useful treatment for cognitive and psychiatric dysfunction in patients with Parkinson's disease. Modafinil improves alertness in Parkinson's disease and warrants further investigation to establish its effects on cognitive performance.
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PMID:Cognitive deficits and psychosis in Parkinson's disease: a review of pathophysiology and therapeutic options. 1673 99


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