Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Delayed disease progression and symptomatic improvement occur with cholinesterase inhibitors (ChEIs) in dementia with Lewy bodies (DLB). In this study, complications (insomnia, dyskinesias, agitation, and delirium) occurred in three patients switched from donepezil to galantamine. The authors describe evidence-based recommendations for ChEI switchover in DLB.
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PMID:Emergent complications following donepezil switchover to galantamine in three cases of dementia with Lewy bodies. 1638 98

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

Extensive research suggests that a number of plant-derived chemicals and traditional Oriental herbal remedies possess cognition-enhancing properties. Widely used current treatments for dementia include extracts of Ginkgo biloba and several alkaloidal, and therefore toxic, plant-derived cholinergic agents. Several non-toxic, European herbal species have pan-cultural traditions as treatments for cognitive deficits, including those associated with ageing. To date they have not received research interest commensurate with their potential utility. Particularly promising candidate species include sage (Salvia lavandulaefolia/officinalis), Lemon balm (Melissa officinalis) and rosemary (Rosmarinus officinalis). In the case of sage, extracts possess anti-oxidant, estrogenic, and anti-inflammatory properties, and specifically inhibit butyryl- and acetyl-cholinesterase. Acute administration has also been found to reliably improve mnemonic performance in healthy young and elderly cohorts, whilst a chronic regime has been shown to attenuate cognitive declines in sufferers from Alzheimer's disease. In the case of Melissa officinalis, extracts have, most notably, been shown to bind directly to both nicotinic and muscarinic receptors in human brain tissue. This property has been shown to vary with extraction method and strain. Robust anxiolytic effects have also been demonstrated following acute administration to healthy humans, with mnemonic enhancement restricted to an extract with high cholinergic binding properties. Chronic regimes of aromatherapy and essential oil respectively have also been shown to reduce agitation and attenuate cognitive declines in sufferers from dementia. Given the side effect profile of prescribed cholinesterase inhibitors, and a current lack of a well tolerated nicotinic receptor agonist, these herbal treatments may well provide effective and well-tolerated treatments for dementia, either alone, in combination, or as an adjunct to conventional treatments.
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PMID:The psychopharmacology of European herbs with cognition-enhancing properties. 1716 69

The treatments of choice in Alzheimer's disease (AD) are cholinesterase inhibitors and NMDA-receptor antagonists, although doubts remain about the therapeutic effectiveness of these drugs. Herbal medicine products have been used in the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD) but with various responses. The objective of this article was to review evidences from controlled studies in order to determine whether herbs can be useful in the treatment of cognitive disorders in the elderly. Randomized controlled studies assessing AD in individuals older than 65 years were identified through searches of MEDLINE, LILACS, Cochrane Library, dissertation Abstract (USA), ADEAR (Alzheimer's Disease Clinical Trials Database), National Research Register, Current Controlled trials, Centerwatch Trials Database and PsychINFO Journal Articles. The search combined the terms Alzheimer disease, dementia, cognition disorders, Herbal, Phytotherapy. The crossover results were evaluated by the Jadad's measurement scale. The systematic review identified two herbs and herbal formulations with therapeutic effects for the treatment of AD: Melissa officinalis, Salvia officinalis and Yi-Gan San and BDW (Ba Wei Di Huang Wan). Ginkgo biloba was identified in a meta-analysis study. All five herbs are useful for cognitive impairment of AD. M. officinalis and Yi-Gan San are also useful in agitation, for they have sedative effects. These herbs and formulations have demonstrated good therapeutic effectiveness but these results need to be compared with those of traditional drugs. Further large multicenter studies should be conducted in order to test the cost-effectiveness of these herbs for AD and the impact in the control of cognitive deterioration.
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PMID:The use of herbal medicine in Alzheimer's disease-a systematic review. 1717 7

Atypical antipsychotics will continue to be prescribed for the behavioral symptoms of dementia in the absence of more effective, better tolerated, and safer alternatives. The evidence base, although incomplete, suggests that modest treatment effect sizes are offset by risk of considerable adverse effects. How might this information be best applied to clinical practice? Non-pharmacologic strategies should be implemented in routine clinical practice. Placebo-controlled clinical trials of individual antipsychotic agents have historically reported high placebo response rates; CATIE-AD reported that the sum total of the risk/benefit equation of atypical antipsychotic therapy was no greater than that achieved by placebo. CATIE-AD was designed to study the effectiveness of atypical antipsychotic treatment in community dwelling patients with AD. It is uncertain whether the results can be generalized to the populations of dementia patients residing in nursing homes with more severe cognitive and behavioral impairment. There is some suggestion that nursing home patients with dementia complicated by severe behavioral symptoms, particularly agitation and aggression without accompanying psychosis, might achieve greater benefit from atypical antipsychotic treatment than patients with milder behavioral symptoms. The finding that dementia patients without psychosis may respond more robustly to antipsychotic treatment seems counterintuitive, but may support the hypothesis that the neurobiology of the "psychosis of AD" differs from the psychosis of schizophrenia or bipolar disease. Adverse effects associated with antipsychotic therapy should be aggressively monitored throughout therapy. Treatment-emergent sedation was associated with all of the atypical antipsychotics in CATIE-AD and is probably an important mediator of mortality risk in patients with dementia. Sedation exacerbates pre-existing cognitive impairment and increases the risk of complications such as aspiration pneumonia, so concomitant use of benzodiazepines should be discouraged or limited to short periods with careful observation.' Once initiated, the effectiveness and tolerability of antipsychotic therapy should be evaluated routinely. In Alzheimer's disease, the severity and frequency of behavioral symptoms often decreases as illness progresses. In a stable patient, it is prudent to attempt to taper and discontinue the antipsychotic after 2-8 months of therapy. Better understanding of the potential adverse effects of antipsychotic therapy has increased interest in the effects of the dementia-specific medications on behavioral symptoms. Reductions in neuropsychiatric symptoms have been reported from trials of individual cholinesterase inhibitors, memantine monotherapy, and memantine combined with donepezil in AD patients. Studies of small numbers of patients in open trials of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and one double-blind placebo controlled trial (rivastigmine) have reported varying degrees of improvement of behavioral symptoms and psychosis of dementia with Lewy bodies (DLB). Delusions, hallucinations, apathy, and agitation/aggression are cited as the symptom categories most likely to show significant improvement. Since few of these studies were prospectively designed to study behavioral symptoms, results must be interpreted cautiously. Treatment of behavioral symptoms in AD and other dementias is challenging. The limitations of current approaches drive the search for effective, well tolerated therapies.
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PMID:Atypical antipsychotics for the treatment of dementia-related behaviors: an update. 1763 94

Alzheimer's disease (AD) is the most common cause of dementia affecting nearly 18 million people around the world and 4.5 million in the US. It is a progressive neurodegenerative condition that is estimated to dramatically increase in prevalence as the elderly population continues to grow. As the cognitive and neuropsychiatric signs and symptoms of AD progresses in severity over time, affected individuals become increasingly dependent on others for assistance in performing all activities of daily living. The burden of caring for someone affected by the disorder is great and has substantial impact on a family's emotional, social and financial well-being. In the US, the currently approved medications for the treatment of mild to moderate stages of AD are the cholinesterase inhibitors (ChEIs). Cholinesterase inhibitors have shown modest efficacy in terms of symptomatic improvement and stabilization for periods generally ranging from 6 to 12 months. There are additional data that have emerged, which suggest longer-term benefits. For the moderate to severe stages of AD, memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist is in widespread use and has shown modest benefit as monotherapy and in combination with ChEIs. The cost effectiveness of the currently available therapeutic agents for AD has undergone great scrutiny and remains controversial, especially outside the US. Neuropsychiatric symptoms such as agitation and psychosis are common in AD. Unfortunately, in the US there are no Food and Drug Administration (FDA)-approved agents for the treatment of these symptoms, although atypical antipsychotics have shown some efficacy and have been widely used. However, the use of these agents has recently warranted special caution due to reports of associated adverse effects such as weight gain, hyperlipidemia, glucose intolerance, cerebrovascular events, and an increased risk for death. Alternative agents used to treat neuropsychiatric symptoms include serotonergic antidepressants, benzodiazepines, and anticonvulsant medications.
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PMID:Treatment of Alzheimer's disease across the spectrum of severity. 1804 10

Numerous recent studies have challenged the widely held belief that atypical antipsychotics are safe and effective options for the treatment of behavioural problems such as agitation in patients with dementia. Accordingly, there is a need to reconsider the place of atypical antipsychotics in the treatment of patients with dementia. The present article is intended to assist clinicians with the assessment and pharmacological management of agitation in patients with dementia. We review the risk-benefit evidence for the use of atypical antipsychotics in patients with dementia-related agitation (DRA). Emerging evidence indicates that, for patients with dementia, the risks associated with atypical antipsychotics may outweigh the benefits except for patients with severe agitation who require short-term chemical restraint. We then discuss the importance of a careful assessment to rule out potentially reversible factors contributing to DRA. Finally, we summarize the evidence supporting the use of medications other than antipsychotics to treat DRA. There is wide variability in the levels of evidence supporting the use of non-antipsychotic medication for the treatment of DRA. The best evidence currently exists for cholinesterase inhibitors and serotonin-specific reuptake inhibitor antidepressants. Emerging reports suggest that numerous other medications, for example, antiepileptics, lithium, anxiolytics, analgesics, beta-adrenoceptor antagonists, cannabinoid receptor agonists and hormonal agents, may prove to be viable alternatives to antipsychotics for the treatment of severe DRA and more research is urgently needed to help assess the effectiveness of these agents. A comprehensive biopsychosocial assessment and treatment plan is likely the most effective way to manage DRA.
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PMID:Alternatives to atypical antipsychotics for the management of dementia-related agitation. 1866 63

The diagnosis of dementia with Lewy bodies (DLB) is difficult if one relies solely on clinical features. Current International Consensus Criteria for DLB have high specificity but a significant percentage of patients might be misdiagnosed. Reasons for clinical uncertainty regard the presence of concomitant motor signs in patients with Alzheimer's disease as well as the observation that cognitive abnormalities in DLB might develop with memory impairment without significant parkinsonism. This has clinical relevance as DLB patients may be particularly sensitive to antipsychotics and even the effectiveness of atypical neuroleptics such as quetiapine for the treatment of agitation and hallucinations has been questioned by double-blind, placebo-controlled, randomized studies. By contrast, acetyl-cholinesterase inhibitors such as rivastigmine have shown benefit not only on cognitive but also on psychiatric symptoms. Recent evidence shows that striatal dopamine transporter binding of (123)I-ioflupane SPECT is reduced in DLB and this is consistent with a significant loss of nigral dopamine neurons in this disorder. Several studies have demonstrated the diagnostic accuracy of (123)I-ioflupane in the differential diagnosis of parkinsonism. Given the availability of SPECT, this investigation represents a useful marker to support clinical diagnosis and can help establishing appropriate treatment for this disorder.
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PMID:The role of I-ioflupane SPECT dopamine transporter imaging in the diagnosis and treatment of patients with dementia with Lewy bodies. 1930 May 62

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.
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PMID:Antipsychotics for the treatment of behavioral and psychological symptoms of dementia (BPSD). 1930 92

Family caregivers of a community-dwelling demented relative experience significant burden in their caregiving role. In particular, behavioural disturbances are expected to be responsible for high caregiver distress and burden. Above, in approximately 80% of the cases, institutionalization of the demented patients with dementia occurs as a result of a burdened caregiver. Because of the impressive disruptive character of behavioural disturbances, most caregivers appeal for pharmacological intervention at a given moment, expecting instant suppression of the aberrant behaviour. Beside the antipsychotic drugs, the cholinesterase inhibitors are commonly used in the treatment of agitation, aggression, delusions, etc. Although in meta-analyses on the efficacy of both categories of drugs, only little evidence of their efficacy has been found and an important placebo effect has been reported that >90% of the demented elderly was treated at least once. The aim of this study was to investigate if pharmacological treatment of behavioural disturbances of the demented can lower the burden and the time spent in the family caregiver irrespective of their effect on the demented himself. A systematic literature search was performed by means of Medline, Embase, Cochrane DSR, Dare, CCTR and ACP Journal Club. Based on this review, pharmacological treatment of demented elderly seems to lower caregiver burden (mean difference 0.27) and the time caregivers spent (mean difference 41.65 minutes). Considering that family caregivers confronted with the troublesome behaviour of their demented relative will apply for pharmacological intervention, future research should particularly focus on the outcome measures of the caregivers' well-being.
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PMID:Can pharmacological treatment of behavioural disturbances in elderly patients with dementia lower the burden of their family caregiver? 1942 98


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