Rivastigmine for Dementia Associated with Parkinson's Disease

University of Bergen, Bergen, Hordaland, Norway
New England Journal of Medicine (Impact Factor: 55.87). 12/2004; 351(24):2509-18. DOI: 10.1056/NEJMoa041470
Source: PubMed


Cholinergic deficits are prominent in patients who have dementia associated with Parkinson's disease. We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients.
Patients in whom mild-to-moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson's disease were randomly assigned to receive placebo or 3 to 12 mg of rivastigmine per day for 24 weeks. Primary efficacy variables were the scores for the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC). Secondary clinical outcomes were the scores for the Alzheimer's Disease Cooperative Study-Activities of Daily Living, the 10-item Neuropsychiatric Inventory, the Mini-Mental State Examination, Cognitive Drug Research power of attention tests, the Verbal Fluency test, and the Ten Point Clock-Drawing test.
A total of 541 patients were enrolled, and 410 completed the study. The outcomes were better among patients treated with rivastigmine than among those who received placebo; however, the differences between these two groups were moderate and similar to those reported in trials of rivastigmine for Alzheimer's disease. Rivastigmine-treated patients had a mean improvement of 2.1 points in the score for the 70-point ADAS-cog, from a baseline score of 23.8, as compared with a 0.7-point worsening in the placebo group, from a baseline score of 24.3 (P<0.001). Clinically meaningful improvements in the scores for the ADCS-CGIC were observed in 19.8 percent of patients in the rivastigmine group and 14.5 percent of those in the placebo group, and clinically meaningful worsening was observed in 13.0 percent and 23.1 percent, respectively (mean score at 24 weeks, 3.8 and 4.3, respectively; P=0.007). Significantly better outcomes were seen with rivastigmine with respect to all secondary efficacy variables. The most frequent adverse events were nausea (affecting 29.0 percent of patients in the rivastigmine group and 11.2 percent of those in the placebo group, P<0.001), vomiting (16.6 and 1.7 percent, P<0.001), and tremor (10.2 and 3.9 percent, P=0.01).
In this placebo-controlled study, rivastigmine was associated with moderate improvements in dementia associated with Parkinson's disease but also with higher rates of nausea, vomiting, and tremor.

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    • "Among the many non-motor problems affecting patients with PD, psychosis is particularly relevant, as it represents a great burden to caregivers and increases the risk that a patient can no longer be looked after at home, but will move to a nursing home. While the cholinesterase inhibitor rivastigmine may relieve psychotic symptoms in PD patients, (Emre 2004) it is not licensed for this indication, and neuroleptics often become necessary. Among the available antipsychotics, only clozapin has been classified as being effective in PD patients [23]; however, specialised monitoring is required due to the risk of agranulocytosis. "
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    • "However, the role of acetylcholine in PD cognition is not straightforward. On one hand there are previous studies indicating that medications that prevent the breakdown of acetylcholine (i.e., cholinesterase inhibitors) improve cognition in demented patients with PD (Emre et al., 2004; Bosboom et al., 2009; Possin et al., 2013). On the other hand we argue here that increased activity in cholinergic interneuron leads to a deficit in procedural-based category learning. "
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