Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple behavioural and psychological symptoms of dementia (BPSD) are commonly associated with all dementia subtypes, and worsen during disease progression. BPSD arise due to impairment of cholinergic function in the cortex, hippocampus and related limbic systems. Recent studies have investigated the effect of cholinesterase inhibitors on BPSD. The dual acetylcholinesterase/butyrylcholinesterase (AChE/BuChE) inhibitor rivastigmine was shown to have several potential advantages over the AChE-selective inhibitors donepezil and galantamine for the treatment of BPSD. Rivastigmine appears to be effective across the range of dementia severity from mild to severe, and across the spectrum of dementia (Alzheimer's disease [AD], the AD variant with Lewy bodies, Parkinson's disease dementia and vascular dementia subtypes). It also appears to have a disease-modifying potential. Rivastigmine improved a wider range of behavioural symptoms (apathy, anxiety/depression, hallucinations and delusions) than donepezil and galantamine (which improved apathy and depression/anxiety only). Unlike donepezil, rivastigmine reduced the need for psychotropic medications to treat BPSD. Dual inhibition of AChE and BuChE and brain-region selectivity through preferential inhibition of the G1 isoform of AChE may provide the underlying reasons for the apparently greater and broader efficacy of rivastigmine over AChE-selective inhibitors for the treatment of BPSD. However, randomised, controlled trials are required to compare dual inhibitors, such as rivastigmine, and AChE-selective agents, to confirm and quantify any differences in their effects on BPSD.
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PMID:The efficacy of cholinesterase inhibitors in treating the behavioural symptoms of dementia. 1213 65

Parkinson's disease patients may suffer from cognitive impairment and behavioural problems such as apathy, personality changes, speech disturbances and visual hallucinations (Parkinson's disease dementia). However, there is currently no recommended treatment for Parkinson's disease dementia and antipsychotic agents can worsen extrapyramidal symptoms, making them unsuitable for patients with this condition. The observation that patients with Parkinson's disease dementia have extensive cholinergic deficits led to the hypothesis that cholinesterase inhibitors may provide benefits for patients with this condition. Here, we present a case series of patients with Parkinson's disease and dementia who we treated with rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) that shows brain region-selectivity. The introduction of rivastigmine led to improvements in cognitive and functional abilities, as well as the resolution of behavioural problems and visual hallucinations. Rivastigmine was well tolerated by our patients when the dose was escalated slowly, including one patient who had previously experienced severe side-effects with the AChE-selective inhibitor donepezil. Despite the large number and range of concomitant medications being received by the patients, no side-effects thought to be related to drug-drug interactions were reported. A large, placebo-controlled study is warranted to ascertain the full clinical profile of rivastigmine in Parkinson's disease dementia.
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PMID:Rivastigmine for the treatment of dementia and visual hallucinations associated with Parkinson's disease: a case series. 1224 Jul 87

The results of recent clinical trials with rivastigmine show that in the approved indication of mild to moderate Alzheimer's disease (AD), the drug is effective in the long term. Rivastigmine produces a significant delay in the decline of the three components of AD that have been identified by European guidelines as essential parameters for the assessment of therapeutic efficacy of medicinal products with this indication. These are cognitive function, the ability to perform the usual activities of daily living, and global judgement of the patient's condition by the patient himself, his caregiver and his doctor. Moreover, rivastigmine produces significant control of AD behavioural disorders. This further reduces caregiver burden, reduces the probability of institutionalisation, and enables the reduction or discontinuation of expensive and poorly tolerated antipsychotics. Recent trials also suggest that rivastigmine is effective in moderate to severe Alzheimer's disease, 'mixed' dementia (AD associated with vascular disorders) and Lewy body dementia. Preliminary investigations have also indicated that the drug may provide important benefits in patients with vascular dementia or dementia associated with Parkinson's disease. Pharmacoeconomic studies show that the therapeutic properties of rivastigmine result in economic savings for the care of demented patients living in the community.
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PMID:Rivastigmine: an update on therapeutic efficacy in Alzheimer's disease and other conditions. 1274 Jan 50

Alzheimer's disease is the most common form of neurodegenerative dementia and poses considerable health challenges to both patients and their families. Rivastigmine is a powerful slow-reversible, noncompetitive carbamate cholinesterase inhibitor that is approved for the treatment of mild-to-moderate Alzheimer's disease. Randomized, double-blind, placebo-controlled trials of up to 6 months duration have shown beneficial effects of rivastigmine compared with placebo in measures of cognition and global functioning. Less rigorous but growing data suggest that the beneficial effects may endure for up to 5 years, extend to more advanced stages of Alzheimer's disease and may occur in noncognitive domains, such as activities of daily living and the behavioral symptoms of Alzheimer's disease. Evidence from controlled studies also supports the use of rivastigmine for cognitive and behavioral symptoms in Alzheimer's disease associated with vascular risk factors, dementia with Lewy bodies and Parkinson's disease dementia. Early and continued treatment of Alzheimer's disease with rivastigmine maximizes the observed beneficial effects. The most prominent adverse effect of rivastigmine is centrally mediated cholinergic gastrointestinal events, which can be minimized by slower dose-escalation intervals and administration with a full meal. Therapeutic dosing is 6-12 mg/day given twice daily, with higher doses having the potential for greater benefits.
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PMID:Rivastigmine for Alzheimer's disease. 1616 80

Treatments for the symptomatic relief of Alzheimer's disease are available but despite advances in our ability to treat persons with various forms of dementia, more effective treatments are needed. The cholinesterase inhibitors donepezil, rivastigmine, and galantamine have demonstrated efficacy in improving cognition and global status and to a lesser extent, behavioral abnormalities relative to placebo in patients with mild-to-moderate Alzheimer's disease. Rivastigmine has been shown to benefit patients with dementia with Lewy Bodies and with dementia associated with Parkinson's disease. Donepezil and galantamine have also been shown to be mildly effective in dementia due to cerebral ischemia. Memantine has a distinct mechanism of action and is effective in moderate-to-severe AD. The benefits from these drugs, however, are limited and their long-term effectiveness has not been well-demonstrated. Their clinical utility is controversial. Many novel approaches that promise to provide more effective treatments are currently being pursued.
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PMID:Current and emerging pharmacological treatment options for dementia. 1672 Sep 56

Cholinesterase inhibition in patients with Alzheimer's disease (AD) may affect heart rate, sometimes inducing bradycardia. Additional cardiac safety considerations apply in patients with dementia with Lewy bodies (DLB) and Parkinson's disease (PDD), in whom cardiovascular autonomic nervous system dysfunction is common. We conducted a review of the safety data available for rivastigmine in these two conditions. A modest reduction in the mean heart rate of 1.5-2 bpm was seen. No clinically meaningful treatment differences in bradycardia or ECG abnormalities were apparent. Compared with placebo, rivastigmine appeared to be associated with fewer vascular disorder adverse events (AEs) (p = 0.002) and fewer AEs of syncope (p = 0.018) in PDD patients (n = 541). A smaller randomised, placebo-controlled study of rivastigmine in DLB (n = 120) showed similar findings. Rivastigmine appears to have a favourable cardiac safety profile in PDD and DLB patients.
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PMID:Cardiac safety of rivastigmine in Lewy body and Parkinson's disease dementias. 1680 45

The purpose of this study was to assess whether rivastigmine, a cholinergic agent, affects tremor features when given to improve cognition in demented Parkinson's disease (PD) patients. Demented PD patients (n = 26; Mini-Mental State Examination score, 13-25; age, 75.2 +/- 4.9 yr) were given rivastigmine (mean dose, 8.0 mg/day) for 12 weeks. They underwent tremor assessment before and during treatment. Global Tremor Score (GTS) was based on eight items specific to tremor in the Unified Parkinson's Disease Rating Scale. Tremor amplitude was also measured using accelerometers during the ON state in both hands in 19 patients. Drug therapy for other PD symptoms was unchanged. The mean group baseline GTS was 1.2 +/- 1.6 points, increasing to 1.6 +/- 2.4 points after treatment (mean increase, 0.4 +/- 1.2 points; P > 0.05). The GTS increased by 3.2 +/- 1.9 points (range, 1-5) in 7 patients (26.9%) and decreased by 1 +/- 0 points in 3 patients (11.5%). Accelerometric assessment showed a significant increase of the average tremor amplitude in the right hand (0.08 +/- 0.03 xg at baseline; 0.12 +/- 0.02 xg at Week 12 of treatment, P = 0.02). Left-hand tremor amplitude did not change. Rivastigmine caused only slight worsening of tremor in demented PD patients, while improving cognition.
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PMID:Effect of rivastigmine on tremor in patients with Parkinson's disease and dementia. 1694 67

Rivastigmine is a carbamate-type dual inhibitor of brain acetyl- and butyrylcholinesterases that has been evaluated in the symptomatic treatment of patients with mild to moderate dementia associated with idiopathic Parkinson's disease. Oral rivastigmine 3-12 mg/day for 24 weeks was significantly more effective than placebo in ameliorating cognitive and functional decline, including attentional deficits, in patients with Parkinson's disease dementia in a randomised, double-blind trial. The beneficial effects of rivastigmine observed in the double-blind trial were generally maintained in a 24-week extension of this study in which all patients received active treatment; placebo recipients who switched to rivastigmine also experienced improvements in their cognitive and functional symptoms at week 48. Rivastigmine appeared to be generally well tolerated, with the most common adverse events being mild to moderate in intensity and cholinergic in nature. Parkinsonian symptoms (mainly tremor) were more common in rivastigmine than placebo recipients.
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PMID:Rivastigmine: in Parkinson's disease dementia. 1695 49

We aimed to determine prospectively whether rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, provided benefits in patients with and without visual hallucinations in a population with dementia associated with Parkinson's disease (PDD). This was a 24-week double-blind placebo-controlled study. Primary efficacy measures were the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC). Secondary efficacy measures included activities of daily living, behavioral symptoms, and executive and attentional functions. Patients were stratified according to the presence of visual hallucinations at baseline. The study included 188 visual hallucinators (118 on rivastigmine, 70 on placebo) and 348 nonvisual hallucinators (239 on rivastigmine, 109 on placebo). Rivastigmine provided benefits in both visual hallucinators and nonvisual hallucinators. Absolute responses to rivastigmine on the ADAS-cog were comparable over 6 months, although rivastigmine-placebo differences tended to be larger in visual hallucinators (4.27; P = 0.002) than in nonhallucinators (2.09; P = 0.015). On the ADCS-CGIC, differences between rivastigmine and placebo were 0.5 in visual hallucinators (P = 0.030) and 0.3 in nonhallucinators (P = 0.111). Rivastigmine provided benefits on all secondary efficacy measures, and placebo declines and treatment differences were more marked in visual hallucinators. Adverse events were reported more frequently by rivastigmine-treated patients, although this difference was less marked in visual hallucinators. Visual hallucinations appear to predict more rapid decline and possibly greater therapeutic benefit from rivastigmine treatment in PDD.
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PMID:Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson's disease. 1737 57

Patients suffering from Parkinson's disease dementia (PDD) have a movement disorder, but it can be difficult to determine whether the functional impairment, which is critical in making the assessment of whether a patient has achieved the threshold for a diagnosis of dementia, is due to the dementia or the underlying Parkinson's disease. Although the cognitive impairment found in nondemented patients with Parkinson's disease is very dysexecutive in nature, the DSM IV (Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association IV) diagnosis of PDD has memory impairment as the defining characteristic of PDD. Severe deficits in cortical, cholinergic, excitatory, neuromodulatory input mean that memory impairment is not always due to encoding and retrieval strategy deficits, but it may also be amnesic without being related to concomitant Alzheimer's disease pathology. Patients with PDD have a high mortality, especially when they develop hallucinations and/or are admitted to nursing homes. Of interest is the reduction in mortality that was more marked in the subgroup with visual hallucinations at baseline. The increased mortality in PD may be due to autonomic failure, evidenced by the reductions in heart rate variability in these patients. This reduction is greater in patients with hallucinations. Rivastigmine is a dual inhibitor of brain acetyl- and butyrylcholinesterases that has been evaluated in the symptomatic treatment of patients with mild-to-moderate dementia associated with idiopathic Parkinson's disease. Although there is a need for more studies using pragmatic measures, such as time to residential care facility and both patient and carer quality of life assessments, rivastigmine appears to improve cognition and activities of daily living in patients with PDD, resulting in a clinically meaningful benefit in a large number of cases.
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PMID:Rivastigmine and Parkinson dementia complex. 1742 77


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