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

---

Query: EC:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disruptive agitation and psychotic symptoms are important problems in the management of Alzheimer's disease and are major determinants of nursing home placement. This article reviews interpretable, placebo-controlled studies of psychopharmacologic approaches to the treatment of these "noncognitive" psychiatric and behavioral problems. Clinical trials of antipsychotic drugs demonstrate modest efficacy for psychosis and agitation, but adverse effects are common. Trials of serotonin selective reuptake inhibitors suggest they may be effective for emotional disturbances complicating Alzheimer's disease. Trials of drugs that enhance central cholinergic activity (certain cholinesterase inhibitors and selective M1 muscarinic cholinergic agonists) demonstrate positive effects on both cognitive deficits and noncognitive psychiatric and behavioral problems. Further clinical studies are needed to provide guidelines for the management of noncognitive psychiatric and behavioral problems in Alzheimer's disease.
...
PMID:Psychopharmacology of noncognitive abnormal behaviors in Alzheimer's disease. 972 Apr 84

Neuropsychiatric abnormalities, as well as the commonly associated neuropsychological symptoms, are clinical characteristics of Alzheimer's disease (AD), the most common form of dementia. Thus, in addition to a general cognitive and functional decline, neuropsychiatric manifestations, such as agitation, apathy, anxiety, psychoses and disinhibition, are frequently evident in AD patients. Such neuropsychiatric symptoms of AD are the source of considerable patient and caregiver distress, resulting in the prescription of neuroleptics, benzodiazepines or other psychotropic agents, and are a major factor in the decision to transfer the care of patients into nursing homes. Recent evidence suggests that some neuropsychiatric changes associated with AD are related to the cholinergic deficits in the brains of AD patients and that such abnormalities may be responsive to cholinergic therapy. Cholinergic drug therapies indicated for the symptomatic treatment of AD, for example tacrine and the newer cholinesterase (ChE) inhibitors such as donepezil, have been demonstrated to improve memory, language and praxis. Furthermore, although less is known about the effect of ChE inhibitors on the neuropsychiatric symptoms of AD, preliminary evidence suggests that they reduce apathy, anxiety, hallucinations, disinhibition and aberrant motor behaviour. Thus, the newer-generation ChE inhibitors that are well tolerated, easy to administer and show promise in reducing the cognitive, as well as neuropsychiatric disturbances of AD, may emerge as important treatments for some neuropsychiatric symptoms in patients with central cholinergic deficits, including AD.
...
PMID:Neuropsychiatric symptoms and cholinergic therapy for Alzheimer's disease. 987 14

Delirium is a common complication of dementia and may produce considerable morbidity. In addition to psychotic symptoms such as hallucinations and delusions, delirium may produce considerable agitation, which may be refractory to conventional medications such as antipsychotics and benzodiazepines. The main approach to delirium is to treat any underlying medical problem that could cause the delirium. However, delirium is not always reversible, and there is no specific treatment for persistent delirium. The authors present a case of delirium complicating a preexisting dementia that resolved rapidly following initiation of the cholinesterase inhibitor donepezil, suggesting that cholinergic dysfunction may have played a role in the etiology of this patient's delirium. Future research needs to be directed at the issue of cholinergic activity in delirium through monitoring of serum anticholinergic activity and its response to procholinergic therapy.
...
PMID:Donepezil improves symptoms of delirium in dementia: implications for future research. 989 35

The cholinesterase inhibitor tacrine (THA) and the M1 muscarinic agonist AF102B (cevimeline), both reported to enhance cognition in animals and humans, were tested in 5 macaques for reduction of spontaneous, random movements. Monkeys were videotaped 1 hour after administration of normal saline vehicle, after low- and high-dose intramuscular AF102B, and after low- and high-dose oral THA. Two independent blind judges counted numbers of spontaneous movements made by each monkey over 12 consecutive 15-second segments for each drug condition. Both THA and AF102B reduced movement significantly at high doses without overt side effects, warranting further research on the agitation-reducing potential of cognition-enhancing cholinomimetic drugs.
...
PMID:Reduction of motoric agitation and restlessness by AF102B and tacrine in the macaque. 999 May 60

The objective of this study was to assess the tolerability and efficacy of rivastigmine in a group of patients with probable dementia with Lewy bodies (DLB), using an open label study. Open label treatment was with rivastigmine up to maximum tolerated dose (mean 9.6 mg daily, range 3-12 mg). Eleven patients with DLB, mean age 78.5 years, were treated with this cholinesterase inhibitor. After 12 weeks of treatment, mean Neuropsychiatric Inventory scores fell by 73% for delusions, 63% for apathy, 45% for agitation and 27% for hallucinations. Five of the patients (45%) experienced very significant clinical improvements that had not been achieved with other treatments, including low dose neuroleptics. Medication was well tolerated and parkinsonian symptoms tended to improve. Cholinesterase inhibition may be a safe and effective alternative to neuroleptic treatment in DLB. Such effects may also prove to be applicable to the management of neuropsychiatric symptoms in Parkinson's disease and Alzheimer's disease.
...
PMID:Rivastigmine in the treatment of dementia with Lewy bodies: preliminary findings from an open trial. 1082 36

In addition to cognitive deficits, dementia is characterized by noncognitive behavioral disorders that are highly prevalent as the disease progresses into its later stages. These "behavioral and psychological signs and symptoms of dementia" are probably more important on a day to day basis than the cognitive deficits: in some patients, they are not a source of major disability but rather just a nuisance and may not require active pharmacological treatment; in others, they can be source of substantial anxiety and distress. Among the many behavioral symptoms of dementia, the group of behaviors included under the label of depression, anxiety, agitation, aggressiveness or uncooperativeness are the most burdensome and frequently lead to the prescription of an antipsychotic drug. They often precipitate institutional placement. The rationale for the use of psychotropic drugs is partially based upon phenomenological similarities of some behaviors observed in elderly demented patients to signs and symptoms of psychiatric disorders such as depressive illnesses, anxiety or psychotic disorders in non-elderly patients. In fact, the "psychiatric symptoms" in Alzheimer's disease or other dementia are often qualitatively different from those that characterize depressive, anxious or psychotic disorders. Many monoaminergic acquired deficits in dementia may also explain why treatment outcome studies suggest that the psychotropic drugs are less effective in patients with Alzheimer's disease or frontal lobe dementia than in patients with psychiatric disorders. The role of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms in Alzheimer's disease may represent a novel and promising therapeutical approach.
...
PMID:[Biological therapies of behavioral and psychological symptoms of dementia: update and prospects]. 1095 9

Sundowning, manifested as a recurring increase in restlessness and agitation in the evening, is described in a 71-year-old man with clinically diagnosed dementia with Lewy bodies. An objective measure of activity using the activity electronic monitoring technique indicated a marked increase in activity level during the evening compared to earlier in the day. After treatment with donepezil, a cholinesterase inhibitor, ratings of behavioural symptoms improved. In addition, there was a marked reduction in evening activity and an increase in daytime activity. Cognition and parkinsonism also improved. Possible explanations for this finding are discussed.
...
PMID:Improvement in sundowning in dementia with Lewy bodies after treatment with donepezil. 1118 Apr 73

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.
...
PMID:Alzheimer's disease and related disorders. 1134 85

Neuropsychiatric and behavioral symptoms are frequent and problematic components of Alzheimer's disease (AD). In two previously reported studies, metrifonate was shown to benefit behavioral symptoms as assessed by the Neuropsychiatric Inventory (NPI). In this post hoc analysis, detailed studies were completed to determine the effects of metrifonate on individual symptoms. This study was a retrospective analysis of pooled NPI data from two double-blind, placebo-controlled, multicenter 26-week studies of metrifonate that had achieved similar levels of cholinesterase inhibition. Mild-to-moderate probable AD patients received placebo (n = 222) or metrifonate (n = 450) 30 to 60 mg by weight or a 50-mg fixed dose once daily. At 26 weeks, metrifonate-treated patients had significantly reduced NPI total scores (P = .001) and fewer neuropsychiatric symptoms when compared with placebo-treated patients, including hallucinations (P = .004), agitation/aggression (P = .006), depression/dysphoria (P = .011), apathy (P = .019), and aberrant motor behavior (P = .008). Metrifonate reduced or stabilized neuropsychiatric disturbances in 60% of symptomatic patients. Almost 40% of metrifonate-treated patients had a clinically relevant reduction (> or = 30% decrease in NPI score) in their neuropsychiatric disturbances (P = .002). High proportions of metrifonate-treated patients manifested clinically relevant reductions in anxiety (58%, P = .009), apathy (51%, P = .020), and depression/dysphoria (50%, P = .021) compared to placebo. The metrifonate-associated reductions in NPI scores were evident by week 12 and were maintained for the 26-week study period. There was an overall effect size of metrifonate of approximately 15% on total NPI scores when compared to placebo. Metrifonate significantly reduced many of the psychiatric and behavioral symptoms of AD. The observations suggest that enhancement of cholinergic functions in AD has beneficial effects on behavior.
...
PMID:Efficacy of metrifonate in improving the psychiatric and behavioral disturbances of patients with Alzheimer's disease. 1141 66

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.
...
PMID:Neuropsychiatric assessment of Alzheimer's disease and related dementias. 1144 57


<< Previous 1 2 3 4 5 6 7 Next >>

---