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)

Parkinson's disease is associated with dementia in about 40% of cases, and in time up to 80% of patients will develop dementia. This dementia is characterized by deficits in attention, executive function and memory. While, as in Alzheimer's disease, cholinergic dysfunction has long been identified to be related to the cognitive impairment in Parkinson's dementia, the fear of exacerbating the motor symptoms of the disorder has greatly hindered research into the anticholinesterases as symptomatic treatments for the cognitive and psychiatric deficits. However, following a number of successful open-label trials with anticholinesterases, a large, international, randomized, double-blind, placebo-controlled trial of the effects of rivastigmine in the dementia associated with Parkinson's disease has been conducted. Rivastigmine was found to significantly improve all of the primary and secondary endpoints in the study, showing benefits to cognitive function, neuropsychiatric complaints and activities of daily living. Cognitive improvements were seen on the Alzheimer's Disease Assessment Scale cognitive subscale, the Mini Mental State Examination, the attention battery of the Cognitive Drug Research computerized assessment system, word fluency and clock drawing. An open-label extension to the study suggested that the beneficial effects persisted up to 48 weeks. While the improvements seen with rivastigmine on the various measures have been described as modest by some commentators, rivastigmine is now widely registered for the symptomatic treatment of mild to moderate dementia associated with Parkinson's disease. A treatment is now available for a previously unmet medical need.
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PMID:Rivastigmine tartrate with a focus on dementia associated with Parkinson's disease. 1761 7

Transdermal patches are used for the treatment of various diseases including neurologic and psychiatric disorders such as Parkinson disease (PD), major depression, and attention deficit hyperactivity disorder. They are believed to offer many advantages over conventional oral therapies. By providing smoother, continuous drug delivery and steadier plasma levels, patches may reduce the incidence of side effects, thus making optimal therapeutic doses easier to attain and potentially improving treatment efficacy and compliance. Drug delivery systems such as patches that are more patient- and caregiver-friendly may enable patients to continue treatment for longer periods and to attain greater, more sustained treatment benefits. To date, approved therapies for Alzheimer disease (AD), including cholinesterase inhibitors and memantine, are orally administered. Potential advantages associated with patches provide a therapeutic rationale to offer additional benefits in AD patients. Rivastigmine is well suited to patch administration because it is a small, potent molecule that is both lipophilic and hydrophilic. A rivastigmine patch has been developed and may provide a promising new approach to dementia therapy.
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PMID:Rationale for transdermal drug administration in Alzheimer disease. 1764 21

Rivastigmine patch is the first transdermal treatment to be approved for Alzheimer's disease (AD) and Parkinson's disease dementia in the USA and for AD in Europe. It provides smooth, continuous drug delivery, and has the potential to maintain rivastigmine concentrations within an optimal therapeutic window while avoiding the peaks and troughs associated with oral drug delivery. The target dose, rivastigmine 9.5 mg/24 h patch (a 10 cm(2) patch), is given once daily and requires a simple one-step dose titration to the therapeutic dose. In a 24-week study in 1195 AD patients, the rivastigmine 9.5 mg/24 h patch provided similar efficacy to the highest dose range of capsules, with approximately three-times fewer reports of nausea and vomiting. Patients in the 9.5 mg/24 h patch and 12 mg/day capsule groups evidenced significant improvements versus placebo on both primary outcome measures: the Alzheimer's Disease Assessment Scale-Cognitive subscale; and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change; in addition to the following secondary outcome measures: Alzheimer's Disease Cooperative Study-Activities of Daily Living scale; Mini-Mental State Examination; and Trail Making Test Part A for assessment of attention, visual tracking and motor processing speed. Treatment differences on the Neuropsychiatric Inventory and Ten Point Clock-drawing Test did not reach statistical significance in this study. The patch may be the optimal way to treat dementia patients with rivastigmine.
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PMID:A rivastigmine patch for the treatment of Alzheimer's disease and Parkinson's disease dementia. 1799 95

The effects of rivastigmine versus placebo in Parkinson's disease dementia (PDD) patients with elevated or normal/low plasma homocysteine were determined. In this prospective analysis of a 24-week, randomly assigned, placebo-controlled study of rivastigmine in PDD, subpopulations comprised patients with plasma homocysteine >or=14 micromol/L (elevated) or <14 micromol/L (normal/low). Coprimary outcomes were the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Alzheimer Disease Cooperative Society-Clinical Global Impression of Change (ADCS-CGIC). Secondary outcomes included additional measures of cognition, including attention and executive function, daily function, and neuropsychiatric symptoms. Adverse events (AEs) were monitored. In total, 342 of 541 patients provided samples for analysis, from which 72% had elevated plasma homocysteine. Hyperhomocysteinemic patients showed treatment differences (rivastigmine vs. placebo) of 4.0 on ADAS-cog and 0.7 on ADCS-CGIC (both P < 0.01), and significant treatment differences on secondary outcomes. Rivastigmine- and placebo-treated hyperhomocysteinemic patients (16.5% and 14.6%) discontinued the study because of AEs. Patients with normal/low homocysteine showed no treatment differences on primary or secondary outcomes (1.4 on the ADAS-cog and 0.1 on ADCS-CGIC, both P = ns); 16.7% and 10.3% rivastigmine- and placebo-treated patients discontinued because of AEs. Elevated homocysteine was associated with greater rivastigmine treatment differences than normal/low homocysteine.
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PMID:Rivastigmine versus placebo in hyperhomocysteinemic Parkinson's disease dementia patients. 1858 67

Dementia associated with Parkinson's disease (PD) ultimately develops in approximately 70% of patients with PD older than 80 years of age. The neuropathology of PD dementia (PDD) is likely multifactorial and affects several neuronal populations. There is evidence that PDD is associated with a cholinergic deficit, supporting the therapeutic role of cholinesterase inhibitors, which are already first-line agents in the treatment of Alzheimer's disease. Open-label and small controlled studies suggested a clinical efficacy of cholinesterase inhibitors in PDD. One large randomized placebo-controlled trial of 541 patients demonstrated that oral rivastigmine improved cognition, attention and executive functions, activities of daily living and behavioral symptoms after 6 months of treatment. Rivastigmine is a dual cholinesterase inhibitor, being effective on both acetylcholinesterase and butyrylcholinesterase. This paper reviews the pharmacokinetic and pharmacodynamic properties of rivastigmine (oral and transdermal administration). It also reviews evidence on clinical efficacy, safety and tolerability of the oral administration in PDD patients at doses of 3-12 mg/day.
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PMID:Rivastigmine in Parkinson's disease dementia. 1867 61

Parkinson's disease (PD) afflicts millions of people worldwide and leads to cognitive impairment or dementia in the majority of patients over time. Parkinson's disease dementia (PDD) is characterized by deficits in attention, executive and visuospatial function, and memory. The clinical diagnostic criteria and neuropathology surrounding PDD remain controversial with evidence of overlap among PDD, dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Cortical cholinergic deficits are greater in PDD than in AD, and are well-correlated with the cognitive and neuropsychiatric dysfunction that occurs in PDD. Inhibition of acetylcholine metabolism is therefore a practical therapeutic strategy in PDD.This review examines current evidence for rivastigmine (a cholinesterase/butyrylcholinesterase inhibitor) treatment in PDD. In addition to its efficacy, we examine the safety profile, side effects, and cost effectiveness of rivastigmine in PDD. Rivastigmine provides modest benefit in PDD and further long-term studies are needed to determine the effectiveness and safety of rivastigmine over time. Tolerability is a problem for many PDD patients treated with rivastigmine. Future studies of rivastigmine in PDD should focus on pragmatic outcomes such as time to need for nursing home placement, pharmacoeconomic outcomes and simultaneous patient/caregiver quality of life assessments.
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PMID:Rivastigmine for the treatment of dementia associated with Parkinson's disease. 1930 Jun 13

Hallucinations in Alzheimer's disease (AD) may indicate greater cortical cholinergic deficits. Rivastigmine has shown larger treatment benefits versus placebo in dementia with Lewy bodies and Parkinson's disease dementia patients with hallucinations. In this retrospective, hypothesis-generating analysis, we investigated whether hallucinations in AD were associated with greater treatment benefits with rivastigmine. Data were pooled from two randomized, double-blind, 6-month, mild-to-moderate AD trials comparing rivastigmine with placebo. Co-primary efficacy parameters were the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). Efficacy data were analyzed for two sub-populations: those with and those without hallucinations at baseline. Of 927 patients, 194 (21%) reported hallucinations at baseline. Hallucinators tended to have greater decline on placebo on all outcome measures. On the ADAS-cog, mean rivastigmine - placebo differences of 3.7 points in hallucinators and 2.2 points in non-hallucinators were reported at 6 months (both p < 0.001). In hallucinators, a significant rivastigmine - placebo difference of -1.0 points (a beneficial effect) was seen on the CIBIC-plus at 6 months (p< 0.001). Non-hallucinators showed a smaller significant treatment difference of -0.3 points (p< 0.05). Interaction testing suggested that differences in treatment effects were significant between hallucinators and non-hallucinators. Hallucinations predicted greater treatment responses to oral rivastigmine.
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PMID:Effects of rivastigmine in Alzheimer's disease patients with and without hallucinations. 2016 85

Rivastigmine has been shown to improve cognition in patients with Parkinson's disease dementia (PDD). To further explore the impact of anticholinesterase therapy on PDD, Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) items were assessed in a retrospective analysis of a 24-week, double-blind, placebo-controlled trial of rivastigmine. Mean changes from baseline at week 24 were calculated for ADAS-cog item scores and for 3 cognitive domain scores. A total of 362 patients were randomized to 3 to 12 mg/d rivastigmine capsules and 179 to placebo. Patients with PDD receiving rivastigmine improved versus placebo on items: word recall, following commands, ideational praxis, remembering test instructions, and comprehension of spoken language (P < .05), with standardized mean differences ranging from 0.04 to 0.30. Rivastigmine also showed significant effects versus placebo on all domains: memory, language, and praxis. The ADAS-cog is sensitive to broad cognitive changes in PDD. Overall, rivastigmine was associated with improvements on individual cognitive items and general cognitive domains.
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PMID:Evaluating rivastigmine in mild-to-moderate Parkinson's disease dementia using ADAS-cog items. 2039 60

Current treatment of Alzheimer's disease comprises pharmacological therapy and psychosocial interventions for patients and caregivers in the context of a symptom and severity dependent management concept. Treatment is targeted towards the core symptoms of dementia (cognitive and functional deficits) and if necessary, towards the behavioral symptoms of dementia. The treatment of Alzheimer's dementia with acetylcholine esterase inhibitors (AChE-I; donepezil, galantamine, rivastigmine) and memantine is evidence-based and recommended. For all drugs, the highest tolerable dose should be given. The choice of AChE-I depends on the side-effects and interaction profile, as there is no convincing evidence of a relevant superiority of one of the drugs over another. Mixed dementia should be treated as Alzheimer's dementia. Treatment of vascular dementia with AChE-I or memantine is off-label and without convincing evidence. There is no convincing evidence for the treatment of frontotemporal dementia or Lewy body dementia. Rivastigmine is effective for the treatment of dementia with Parkinson's disease.
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PMID:[S3 guidelines on dementia. Symptomatic therapy of dementia]. 2127 96

Rivastigmine treatment is associated with significant improvements on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) in patients with mild-to-moderate Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Both AD and PDD are purported to have different profiles of cognitive impairment, which may respond differentially to rivastigmine treatment. This was a retrospective analysis of 3 randomized, double-blind, rivastigmine trial databases (Investigation of transDermal Exelon in ALzheimer's disease [IDEAL; AD], EXelon in PaRkinson's disEaSe dementia Study [EXPRESS; PDD], and Alzheimer's Disease with ENA 713 [ADENA; AD]). Factor analyses of the 11 baseline ADAS-cog items derived the same factors in the 2 diseases, that is, "memory" and "language". Rivastigmine-treated AD and PDD patients showed significant improvements (P < .0001 versus placebo) on both factors. For both AD and PDD, rivastigmine had a numerically greater effect on memory than language. Treatment effect sizes were numerically greater in PDD compared with AD. Rivastigmine treatment is associated with improvement in memory and language in AD and PDD. The numerically greater response in PDD is consistent with greater cholinergic deficits in this disease state.
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PMID:Rivastigmine in Alzheimer's disease and Parkinson's disease dementia: an ADAS-cog factor analysis. 2200 28


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