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)

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

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

Delusions are commonly encountered symptoms in patients with Alzheimer's disease and may lead to significant morbidity. The purpose of this article is to review all clinical trials to date focusing on the management of delusions in patients with Alzheimer's disease to determine the level of evidence for treatment. To achieve this objective, Medline was searched using the key words delusions, dementia, Alzheimer's disease and psychosis. Three main categories of treatment were identified: atypical antipsychotics, cholinesterase inhibitors, and other miscellaneous treatments. It was concluded that all forms of treatment were effective although the greatest burden of evidence existed for risperidone and donepezil. Side effects were noted in all forms of treatment and included somnolence and extrapyramidal effects for antipsychotic medications, whereas gastrointestinal effects were more prevalent in studies involving cholinesterase inhibitors. Further large scale, double-blind, randomized, controlled studies are required before a definitive conclusion can be reached. To our knowledge this is the only systematic review of this area.
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PMID:Treatment of delusions in Alzheimer's disease--response to pharmacotherapy. 1690 81

Parkinson's disease dementia (PDD) ultimately develops in about 80% of patients with Parkinson's disease (PD), and cross-sectional studies have found that some 30% of these patients will experience neuropsychiatric symptoms, such as visual hallucinations and psychosis. The most consistently reported risk factors for dementia in PD are age, severe parkinsonism and mild cognitive impairment. In PDD, both subcortical cognitive and cortical cognitive profiles are described. Specific disorders of sleep, such as rapid eye movement sleep behaviour disorder, excessive daytime sleepiness and sleep attacks, occur frequently. Alzheimer and Lewy body pathology coexist, but the Lewy body pathology in limbic and cortical areas seems to be the main cause of dementia. Neurochemical changes in the biogenic amines and acetylcholine are common, and magnetic resonance imaging studies have shown cortical atrophy in wide cortical areas, including the hippocampus. All PD patients should be screened for mild cognitive impairment and dementia. A large randomised clinical trial showed that the cholinesterase inhibitor rivastigmine has desirable effects on cognition and neuropsychiatric symptoms in PDD patients. Atypical antipsychotic agents may improve psychosis in PDD, but the evidence for this is poor and adverse effects from such therapy are common and may be severe. Non-pharmacological interventions can also be effective but require further study.
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PMID:Management of Parkinson's disease dementia : practical considerations. 1706 84

Parkinson's disease (PD) is a chronic, neurodegenerative disease with degeneration of the central dopaminergic neurons in the substantia nigra, leading to a depletion of dopamine (DA) in the striatum. This depletion causes the clinical hallmarks of this disease: bradykinesia, hypokinesia, rigidity, tremor and postural instability. Besides these well known motor symptoms, non-motor symptoms may develop, such as hyposmia, sleep disorders, autonomic disturbances, depression, cognitive impairment and psychosis. Pathophysiological mechanisms underlying these symptoms not only comprise Lewy body pathology in the central dopaminergic system, but also in the noradrenergic, serotinergic and cholinergic transmittersystems. Indeed, in Parkinson's disease, about 30-40% of the patients suffers fluctuating psychotic symptoms, mainly paranoid delusions and/or visual or acoustic hallucinations, symptoms considered to represent major contributors to patient and caregiver distress and nursing home placement. Endogenous (related to the disease process itself) as well as exogenous (related to therapeutical interventions) psychotogenic factors may contribute to the development of psychotic symptoms in PD. Therapeutical strategies, therefore, are aimed to reduce both endogenous and exogenous factors. To reduce endogenous psychotogenic factors, cholinesterase inhibitors, suggested to reduce cognitive deterioration, now seem to be the drugs of choice. In exogenously induced psychotic symptoms, atypical antipsychotics are considered the most effective. However, as psychotic symptoms in PD are often influenced by both endogenous and exogenous factors, a combination of both strategies may be preferred.
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PMID:PD-related psychosis: pathophysiology with therapeutical strategies. 1744 13


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