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)

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

In Oriental medicine, roots of Polygala tenuifolia Willdenow have been known to be an important herb that exhibits sedative effects in insomnia, palpitation with anxiety, restlessness, and disorientation in humans. We previously reported that BT-11, extracted from those roots, improved scopolamine-induced amnesia in rats and inhibited acetylcholinesterase activities in vitro. Therefore, we proposed that BT-11 could remedy stress-induced memory deficits in rats. In this study, the stress-induced memory impairments in rats were significantly reversed almost to the control level by BT-11 treatment. To seek an active component of BT-11 that plays an important role in antipsychotic effects, we compared BT-11 with 3,4,5-trimethoxycinnamic acid (TMCA), which is a constituent of those root extracts. However, the effects of TMCA were less or were not consistent with those of BT-11 in some of tests. In particular, BT-11 reversed the stress-induced reduction of glucose utilization by [(18)fluorodeoxyglucose]FDG-PET and the levels of neural cell adhesion molecule (NCAM) in rat brains to the control levels, whereas TMCA did not. Therefore, BT-11 improved stress-induced memory impairments through increment of glucose utilization and total NCAM levels in rat brains. In conclusion, BT-11 may be strongly effective against stress-induced amnesia in rats, through the combined effects of TMCA and other active components of BT-11.
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PMID:BT-11 improves stress-induced memory impairments through increment of glucose utilization and total neural cell adhesion molecule levels in rat brains. 1871 49

Amalgam, a multi-domain member of the immunoglobulin superfamily, possesses homophilic and heterophilic cell adhesion properties. It is required for axon guidance during Drosophila development in which it interacts with the extracellular domain of the transmembrane protein, neurotactin, to promote adhesion. Amalgam was heterologously expressed in Pichia pastoris, and the secreted protein product, bearing an NH(2)-terminal His(6)Tag, was purified from the growth medium by metal affinity chromatography. Size exclusion chromatography separated the purified protein into two fractions: a major, multimeric fraction and a minor, dimeric one. Two protocols to reduce the percentage of multimers were tested. In one, protein induction was performed in the presence of the zwitterionic detergent CHAPS, yielding primarily the dimeric form of amalgam. In a second protocol, agitation was gradually reduced during the course of the induction and antifoam was added daily to reduce the air/liquid interfacial foam area. This latter protocol lowered the percentage of multimer 2-fold, compared to constant agitation. Circular dichroism measurements showed that the dimeric fraction had a high beta-sheet content, as expected for a protein with an immunoglobulin fold. Dynamic light scattering and sedimentation velocity measurements showed that the multimeric fraction displays a monodisperse distribution, with R(H)=16 nm. When co-expressed together with amalgam the ectodomain of neurotactin copurified with it. Furthermore, both purified fractions of amalgam were shown to interact with Torpedo californica acetylcholinesterase, a structural homolog of neurotactin.
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PMID:Amalgam, an axon guidance Drosophila adhesion protein belonging to the immunoglobulin superfamily: over-expression, purification and biophysical characterization. 1893 49

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

Understanding drug pharmacology and mechanism of action can help explain not only therapeutic effects and side effects, but also potential adverse effects when drugs are discontinued. This series of articles will broadly review the potential adverse effects associated with the discontinuation of various psychotropic drugs. This first article focuses on adrenergic, cholinergic, and histamine drugs. After chronic use, abruptly stopping adrenergic receptor drugs can cause rebound anxiety, restlessness, and heart palpitations. Abruptly stopping anticholinergic drugs can lead to an anticholinergic discontinuation syndrome characterized by cholinergic rebound, symptoms of which include nausea, sweating, and urinary urgency. Discontinuation of acetylcholinesterase enzyme inhibitor drugs may be associated with mild anticholinergic-like effects such as dry mouth, constipation, and blurred vision. Abrupt discontinuation of histamine-blocking drugs can be associated with activation, insomnia, and a mild anticholinergic withdrawal syndrome. Tapering, rather than abruptly discontinuing, medication can avoid or minimize medication discontinuation effects.
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PMID:Potential adverse effects of discontinuing psychotropic drugs. Part 1: Adrenergic, cholinergic, and histamine drugs. 2050 69

The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review and revise its first (2006) Guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A to D, with A having the strongest evidence base (from randomized controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and brain imaging can improve diagnostic accuracy (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for mild to moderate Alzheimer's disease (A) and memantine for moderate to severe Alzheimer's disease (A). Until further evidence is available other drugs, including statins, anti-inflammatory drugs, vitamin E and Ginkgo biloba, cannot be recommended either for the treatment or prevention of Alzheimer's disease (A). Neither cholinesterase inhibitors nor memantine are effective in those with mild cognitive impairment (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and may cause agitation (A), though selective serotonin reuptake inhibitors may help behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be used for the treatment of people with Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies (DLB)), especially for neuropsychiatric symptoms (A). Cholinesterase inhibitors and memantine can produce cognitive improvements in DLB (A). There is no clear evidence that any intervention can prevent or delay the onset of dementia. Although the consensus statement focuses on medication, psychological interventions can be effective in addition to pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel pharmacological approaches involving strategies to reduce amyloid and/or tau deposition are in progress. Although results of pivotal studies are awaited, results to date have been equivocal and no disease-modifying agents are either licensed or can be currently recommended for clinical use.
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PMID:Clinical practice with anti-dementia drugs: a revised (second) consensus statement from the British Association for Psychopharmacology. 2108 41

Current evidence tends to support the notion that Alzheimer's disease may be postponed by implementing interventions toward the potential etiologic factors (both risk and protective factors) (i.e., primary prevention) and by early detection (i.e., secondary prevention). Epidemiologic research has provided sufficient evidence that vascular risk factors in middle-aged and older adults play a significant role in the development and progression of dementia and AD, whereas extensive social network and active engagement in mental, social, and physical activities may postpone the onset of the dementing disorder. The tertiary prevention may help stabilize cognitive functions, reduce agitation, control neuropsychiatric symptoms. This tertiary prevention aims to avoid functional disability, and if possible, to improve quality of life for patients with AD. Cognitive training may help maintain cognitive function, slow down cognitive decline, and improve wellbeing for people with mild dementia. Current pharmacological treatment widely used for AD and dementia, including cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and the N-methyl-D-aspartate-receptor antagonist (memantine), psychotropic medications are designed to target clinical symptoms of the disease such as cognitive and neuropsychiatric disturbances.
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PMID:[Treatment of Alzheimer's disease: the current situation?]. 2108 15

Behavioral and psychological symptoms of dementia (BPSD) include agitation, aberrant motor behavior, anxiety, elation, irritability, depression, apathy, disinhibition, delusions, hallucinations, and sleep or appetite impairment. These symptoms have adverse consequences for patients and caregivers, such as greater impairment in activities of daily living, worsening quality of life and earlier institutionalization. While the etiology of BPSD has not been clearly delineated, studies assessing the benefits of acetylcholinesterase inhibitors on BPSD suggest that some of the neuropsychiatric symptoms of dementia such as agitation, apathy and psychosis may represent a specific central cholinergic deficiency syndrome. Biochemical and neuroimaging studies of BPSD in Alzheimer's patients support these pharmacological data. This review discusses the literature describing the association between cholinergic deficiency and manifestations of BPSD.
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PMID:Revisiting the cholinergic hypothesis of behavioral and psychological symptoms in dementia of the Alzheimer's type. 2129 41


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