Rivastigmine for Dementia Associated with Parkinson's Disease

Editor's introduction

We are proud and happy to welcome Professor Murat Emre from Istanbul University, Turkey as the newest member of the CNSforum Editorial Board. Professor Murat Emre is an internationally renowned expert on Parkinson's disease, and from next month he will select and comment on articles on this topic. As an introduction to the readers, we have asked Professor Emre for this article on his and his colleagues' recent study to investigate the effect of rivastigmine in patients with dementia associated with Parkinson's disease.

The study

541 patients with a diagnosis of dementia associated with Parkinson’s disease were entered in a randomized, double-blind, placebo controlled multicenter study. Patients were randomized to receive rivastigmine or placebo with a ratio of 2:1.

The primary endpoints included ADAS-cog for cognitive functions and ADCS-CGIC for the assessment of clinical global impression of change. Secondary clinical outcomes were ADCS-ADL, NPI, MMSE, CDR power of attention tests, verbal fluency test and the Ten Point Clock-Drawing test.

The outcome

Rivastigmine treated patients had a mean improvement of 2.1 points 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). More patients on rivastigmine improved on ADCS-CGIC, clinically meaningful improvements were observed in 19.8% of patients on rivastigmine and 14.5% of those on placebo, clinically meaningful worsening was observed in 13% and 23%, respectively.

Significantly better outcomes were seen with rivastigmine with respect to all secondary efficacy measures. Adverse events were mainly gastrointestinal, there was no worsening of motor functions as compared to placebo, 10.2% of patients on rivastigmine experienced a worsening of tremor as compared to 3.9% on placebo

Dementia frequently associated with PD

Despite the initial perception that Parkinson’s disease is mainly a motor disorder, it became apparent that dementia is frequently associated with PD, affecting 40% of patients in cross-sectional (ref. 1) and up to 78% in prospective, observational studies (ref. 2). Dementia associated with PD is accompanied by prominent cholinergic deficits, more prominent than those accompanying Alzheimer’s disease (ref. 3).

There have been previous reports of cholinesterase inhibitors (ChE-I) in dementia associated with Parkinson’s disease (PD-D), as summarized in a recent review (ref. 4). This is, however, the first large, randomized, placebo controlled trial of a ChE-I in PD-D.

Beneficial effects

The results revealed beneficial effects of rivastigmine on all key symptom domains of PD-D. Cognitive dysfunction as well as behavioral symptoms improved, these were reflected in improvements in overall function. Importantly these improvements were not on the cost of deterioration on motor functions, which were initially feared. This study demonstrated that ChE-I represent a viable treatment approach in patients with PD and associated dementia.

References

1. Cummings JL. Intellectual impairment in Parkinson's disease: clinical, pathologic, and biochemical correlates. J Geriatr Psychiatry Neurol 1988; 1(1): 24-36.

2. Aarsland D, Andersen K, Larsen JP, et al. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol 2003; 60(3): 387-92.

3. Tiraboschi P, Hansen LA, Alford M et al. Cholinergic dysfunction in diseases with Lewy bodies. Neurology 2000; 54: 407-11.

4. Aarsland D, Mosimann U, McKeith IG. Role of cholinesterase inhibitors in Parkinson’s disease and Dementia with Lewy Bodies. J Geriatr Psychiatry Neurol 2004; 17: 164-171.