Rivastigmine for Dementia Associated with Parkinson's Disease

doi:10.1056/NEJMoa041470

Volume 351:2509-2518		December 9, 2004		Number 24

Rivastigmine for Dementia Associated with Parkinson's Disease

Murat Emre, M.D., Dag Aarsland, M.D., Ph.D., Alberto Albanese, M.D., E. Jane Byrne, F.R.C.Psych., M.B., Ch.B., Günther Deuschl, M.D., Peter P. De Deyn, M.D., Ph.D., Franck Durif, M.D., Ph.D., Jaime Kulisevsky, M.D., Ph.D., Teus van Laar, M.D., Ph.D., Andrew Lees, M.D., Werner Poewe, M.D., Alain Robillard, M.D., F.R.C.P.C., Mario M. Rosa, M.D., Erik Wolters, M.D., Ph.D., Peter Quarg, M.Sc., Sibel Tekin, M.D., and Roger Lane, M.D.

Full Text

PDF

PDA Full Text

PowerPoint Slide Set

Editorial
by Press, D. Z.

Letters

Add to Personal Archive

Add to Citation Manager

Notify a Friend

E-mail When Cited

E-mail When Letters Appear

PubMed Citation

ABSTRACT

Background Cholinergic deficits are prominent in patients whohave dementia associated with Parkinson's disease. We investigatedthe effects of the dual cholinesterase inhibitor rivastigminein such patients.

Methods Patients in whom mild-to-moderate dementia developedat least 2 years after they received a clinical diagnosis ofParkinson's disease were randomly assigned to receive placeboor 3 to 12 mg of rivastigmine per day for 24 weeks. Primaryefficacy variables were the scores for the cognitive subscaleof the Alzheimer's Disease Assessment Scale (ADAS-cog) and Alzheimer'sDisease Cooperative Study–Clinician's Global Impressionof Change (ADCS-CGIC). Secondary clinical outcomes were thescores for the Alzheimer's Disease Cooperative Study–Activitiesof Daily Living, the 10-item Neuropsychiatric Inventory, theMini–Mental State Examination, Cognitive Drug Researchpower of attention tests, the Verbal Fluency test, and the TenPoint Clock-Drawing test.

Results A total of 541 patients were enrolled, and 410 completedthe study. The outcomes were better among patients treated withrivastigmine than among those who received placebo; however,the differences between these two groups were moderate and similarto those reported in trials of rivastigmine for Alzheimer'sdisease. Rivastigmine-treated patients had a mean improvementof 2.1 points in the score for the 70-point ADAS-cog, from abaseline score of 23.8, as compared with a 0.7-point worseningin the placebo group, from a baseline score of 24.3 (P<0.001).Clinically meaningful improvements in the scores for the ADCS-CGICwere observed in 19.8 percent of patients in the rivastigminegroup and 14.5 percent of those in the placebo group, and clinicallymeaningful 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 rivastigminewith respect to all secondary efficacy variables. The most frequentadverse events were nausea (affecting 29.0 percent of patientsin the rivastigmine group and 11.2 percent of those in the placebogroup, P<0.001), vomiting (16.6 and 1.7 percent, P<0.001),and tremor (10.2 and 3.9 percent, P=0.01).

Conclusions In this placebo-controlled study, rivastigmine wasassociated with moderate improvements in dementia associatedwith Parkinson's disease but also with higher rates of nausea,vomiting, and tremor.

Source Information

From the Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey (M.E.); Rogaland Central Hospital, Stavanger, Norway (D.A.); the School of Medicine, University of Bergen, Bergen, Norway (D.A.); Istituto Nazionale Neurologico Carlo Besta and Università Cattolica, Milan, Italy (A.A.); the University of Manchester, Manchester, United Kingdom (E.J.B.); Christian-Albrechts-Universität Kiel, Kiel, Germany (G.D.); Middelheim Hospital, Zeikenhuis Netwerk Antwerpen, and the Born–Bunge Foundation, University of Antwerp, Wilrijk-Antwerp, Belgium (P.P.D.); Centre Hospitalier Universitaire Clermont-Ferrand, Clermont-Ferrand, France (F.D.); Sant Pau Hospital, Barcelona, Spain (J.K.); Groningen University Hospital, Groningen, the Netherlands (T.L.); the Reta Lila Weston Institute for Neurological Studies, University College London, London (A.L.); Innsbruck Medical University, Innsbruck, Austria (W.P.); Hôpital Maisonneuve-Rosemont, Montreal (A.R.); Hospital de Santa Maria, Lisbon, Portugal (M.M.R.); the Research Institute for Neurosciences, Vrije Universiteit Medical Center, Amsterdam (E.W.); Novartis Pharma, Basel, Switzerland (P.Q.); and Novartis Pharmaceuticals, East Hanover, N.J. (S.T., R.L.).

Address reprint requests to Dr. Emre at Istanbul T $i$ p Fakültesi, Nöroloji Anabilim Dal $i$ , 34390 Capa, Istanbul, Turkey, or at muratemre{at}superonline.com.

Full Text of this Article

Related Letters:

Rivastigmine for Dementia Associated with Parkinson's Disease
Harada C. N., Shega J. W., Sachs G. A., Emre M., Aarsland D., Poewe W.
Extract | Full Text | PDF
N Engl J Med 2005; 352:1387, Mar 31, 2005. Correspondence

This article has been cited by other articles:

Chen, J. J., Trombetta, D. P., Fernandez, H. H. (2008). Palliative Management of Parkinson Disease: Focus on Nonmotor, Distressing Symptoms. Journal of Pharmacy Practice 21: 262-272 [Abstract]
Vale, S. (2008). Current Management of the Cognitive Dysfunction in Parkinson's Disease: How Far Have We Come?. Exp. Biol. Med. 233: 941-951 [Abstract] [Full Text]
Davie, C. A. (2008). A review of Parkinson's disease. Br Med Bull 86: 109-127 [Abstract] [Full Text]
Qaseem, A., Snow, V., Cross, J. T. Jr., Forciea, M. A., Hopkins, R. Jr., Shekelle, P., Adelman, A., Mehr, D., Schellhase, K., Campos-Outcalt, D., Santaguida, P., Owens, D. K., the Joint American College of Physicians/American, (2008). Current Pharmacologic Treatment of Dementia: A Clinical Practice Guideline from the American College of Physicians and the American Academy of Family Physicians. ANN INTERN MED 148: 370-378 [Abstract] [Full Text]
Raina, P., Santaguida, P., Ismaila, A., Patterson, C., Cowan, D., Levine, M., Booker, L., Oremus, M. (2008). Effectiveness of Cholinesterase Inhibitors and Memantine for Treating Dementia: Evidence Review for a Clinical Practice Guideline. ANN INTERN MED 148: 379-397 [Abstract] [Full Text]
Lemstra, A. W., Richard, E., van Gool, W. A. (2007). Cholinesterase inhibitors in dementia: yes, no, or maybe?. Age Ageing 36: 625-627 [Full Text]
Weintraub, D., Hurtig, H. I. (2007). Presentation and Management of Psychosis in Parkinson's Disease and Dementia With Lewy Bodies. Am. J. Psychiatry 164: 1491-1498 [Full Text]
Bronnick, K., Emre, M., Lane, R., Tekin, S., Aarsland, D. (2007). Profile of cognitive impairment in dementia associated with Parkinson's disease compared with Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 78: 1064-1068 [Abstract] [Full Text]
Feldman, H. H, Lane, R., on behalf of the Study 304 Group, (2007). Rivastigmine: a placebo controlled trial of twice daily and three times daily regimens in patients with Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 78: 1056-1063 [Abstract] [Full Text]
Schapira, A. H. V. (2007). Treatment Options in the Modern Management of Parkinson Disease. Arch Neurol 64: 1083-1088 [Full Text]
Warren, N M, Piggott, M A, Lees, A J, Burn, D J (2007). The basal ganglia cholinergic neurochemistry of progressive supranuclear palsy and other neurodegenerative diseases. J. Neurol. Neurosurg. Psychiatry 78: 571-575 [Abstract] [Full Text]
Ballard, C. G., Chalmers, K. A., Todd, C., McKeith, I. G., O'Brien, J. T., Wilcock, G., Love, S., Perry, E. K. (2007). Cholinesterase inhibitors reduce cortical A{beta} in dementia with Lewy bodies. Neurology 68: 1726-1729 [Abstract] [Full Text]
Kurlan, R., Cummings, J., Raman, R., Thal, L., For the Alzheimer's Disease Cooperative Study Grou, (2007). Quetiapine for agitation or psychosis in patients with dementia and parkinsonism. Neurology 68: 1356-1363 [Abstract] [Full Text]
Lippa, C. F., Duda, J. E., Grossman, M., Hurtig, H. I., Aarsland, D., Boeve, B. F., Brooks, D. J., Dickson, D. W., Dubois, B., Emre, M., Fahn, S., Farmer, J. M., Galasko, D., Galvin, J. E., Goetz, C. G., Growdon, J. H., Gwinn-Hardy, K. A., Hardy, J., Heutink, P., Iwatsubo, T., Kosaka, K., Lee, V. M.-Y., Leverenz, J. B., Masliah, E., McKeith, I. G., Nussbaum, R. L., Olanow, C. W., Ravina, B. M., Singleton, A. B., Tanner, C. M., Trojanowski, J. Q., Wszolek, Z. K., for the DLB/PDD Working Group, (2007). DLB and PDD boundary issues: Diagnosis, treatment, molecular pathology, and biomarkers. Neurology 68: 812-819 [Abstract] [Full Text]
Aarsland, D., Emre, M., Lees, A., Poewe, W., Ballard, C., Montgomery, E. B., Miyasaki, J. M., Gronseth, G. (2007). Practice Parameter: Evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 68: 80-81 [Full Text]
Aarsland, D, Bronnick, K, Ehrt, U, De Deyn, P P, Tekin, S, Emre, M, Cummings, J L (2007). Neuropsychiatric symptoms in patients with Parkinson's disease and dementia: frequency, profile and associated care giver stress. J. Neurol. Neurosurg. Psychiatry 78: 36-42 [Abstract] [Full Text]
Leroi, I, Burns, A (2007). Behavioural and psychological symptoms of dementia associated with Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 78: 2-3 [Full Text]
Ferreri, F., Agbokou, C., Gauthier, S. (2006). Recognition and management of neuropsychiatric complications in Parkinson's disease. CMAJ 175: 1545-1552 [Abstract] [Full Text]
Molloy, S A, Rowan, E N, O'Brien, J T, McKeith, I G, Wesnes, K, Burn, D J (2006). Effect of levodopa on cognitive function in Parkinson's disease with and without dementia and dementia with Lewy bodies. J. Neurol. Neurosurg. Psychiatry 77: 1323-1328 [Abstract] [Full Text]
Bronnick, K, Ehrt, U, Emre, M, De Deyn, P P, Wesnes, K, Tekin, S, Aarsland, D (2006). Attentional deficits affect activities of daily living in dementia-associated with Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 77: 1136-1142 [Abstract] [Full Text]
Miyasaki, J. M., Shannon, K., Voon, V., Ravina, B., Kleiner-Fisman, G., Anderson, K., Shulman, L. M., Gronseth, G., Weiner, W. J. (2006). Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.. Neurology 66: 996-1002 [Abstract] [Full Text]
Claassen, J. A. H. R., Jansen, R. W. M. M. (2006). Cholinergically mediated augmentation of cerebral perfusion in Alzheimer's disease and related cognitive disorders: the cholinergic-vascular hypothesis.. J. Gerontol. A Biol. Sci. Med. Sci. 61: 267-271 [Abstract] [Full Text]
Samuel, M., Maidment, I., Boustani, M., Fox, C. (2006). Clinical management of Parkinson's disease dementia: pitfalls and progress. Adv. Psychiatr. Treat. 12: 121-129 [Abstract] [Full Text]
Mosimann, U. P., Rowan, E. N., Partington, C. E., Collerton, D., Littlewood, E., O'Brien, J. T., Burn, D. J., McKeith, I. G. (2006). Characteristics of Visual Hallucinations in Parkinson Disease Dementia and Dementia With Lewy Bodies. AJGP 14: 153-160 [Abstract] [Full Text]
Huang, X., Chen, P., Kaufer, D. I., Troster, A. I., Poole, C. (2006). Apolipoprotein E and Dementia in Parkinson Disease: A Meta-analysis. Arch Neurol 63: 189-193 [Abstract] [Full Text]
McKeith, I. G., Dickson, D. W., Lowe, J., Emre, M., O'Brien, J. T., Feldman, H., Cummings, J., Duda, J. E., Lippa, C., Perry, E. K., Aarsland, D., Arai, H., Ballard, C. G., Boeve, B., Burn, D. J., Costa, D., Del Ser, T., Dubois, B., Galasko, D., Gauthier, S., Goetz, C. G., Gomez-Tortosa, E., Halliday, G., Hansen, L. A., Hardy, J., Iwatsubo, T., Kalaria, R. N., Kaufer, D., Kenny, R. A., Korczyn, A., Kosaka, K., Lee, V.M.Y., Lees, A., Litvan, I., Londos, E., Lopez, O. L., Minoshima, S., Mizuno, Y., Molina, J. A., Mukaetova-Ladinska, E. B., Pasquier, F., Perry, R. H., Schulz, J. B., Trojanowski, J. Q., Yamada, M., for the Consortium on DLB, (2005). Diagnosis and management of dementia with Lewy bodies: Third report of the DLB consortium. Neurology 65: 1863-1872 [Abstract] [Full Text]
Uc, E. Y., Rizzo, M., Anderson, S. W., Qian, S., Rodnitzky, R. L., Dawson, J. D. (2005). Visual dysfunction in Parkinson disease without dementia. Neurology 65: 1907-1913 [Abstract] [Full Text]
Hilker, R., Thomas, A. V., Klein, J. C., Weisenbach, S., Kalbe, E., Burghaus, L., Jacobs, A. H., Herholz, K., Heiss, W. D. (2005). Dementia in Parkinson disease: Functional imaging of cholinergic and dopaminergic pathways. Neurology 65: 1716-1722 [Abstract] [Full Text]
Overshott, R, Burns, A (2005). Treatment of dementia. J. Neurol. Neurosurg. Psychiatry 76: v53-v59 [Full Text]
Wesnes, K. A., McKeith, I., Edgar, C., Emre, M., Lane, R. (2005). Benefits of rivastigmine on attention in dementia associated with Parkinson disease. Neurology 65: 1654-1656 [Abstract] [Full Text]
Schapira, A H V (2005). Present and future drug treatment for Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 76: 1472-1478 [Abstract] [Full Text]
Weintraub, D., Stern, M. B. (2005). Psychiatric Complications in Parkinson Disease. AJGP 13: 844-851 [Abstract] [Full Text]
Overshott, R., Burns, A. (2005). Cholinesterase inhibitors: in search of cholinergic deficits. Adv. Psychiatr. Treat. 11: 321-324 [Full Text]
Lai, M. W., Moen, M., Burns Ewald, M. (2005). Pesticide-like Poisoning from a Prescription Drug. NEJM 353: 317-318 [Full Text]
Cummings, J L (2005). Cholinesterase inhibitors for treatment of dementia associated with Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 76: 903-904 [Full Text]
Mosimann, U. P., Muri, R. M., Burn, D. J., Felblinger, J., O'Brien, J. T., McKeith, I. G. (2005). Saccadic eye movement changes in Parkinson's disease dementia and dementia with Lewy bodies. Brain 128: 1267-1276 [Abstract] [Full Text]
Chow, T. (2005). Rivastigmine modestly improves dementia associated with Parkinson's disease, but has important adverse effects. Evid. Based Ment. Health 8: 41-41 [Full Text]
Gauthier, S. (2005). Drugs for Alzheimer's disease and related dementias. BMJ 330: 857-858 [Full Text]
Harada, C. N., Shega, J. W., Sachs, G. A., Emre, M., Aarsland, D., Poewe, W. (2005). Rivastigmine for Dementia Associated with Parkinson's Disease. NEJM 352: 1387-1387 [Full Text]
Ellis, J. M. (2005). Cholinesterase Inhibitors in the Treatment of Dementia. JAOA: Journal of the American Osteopathic Association 105: 145-158 [Abstract] [Full Text]
(2005). Rivastigmine for Parkinson Disease Dementia. JWatch Psychiatry 2005: 11-11 [Full Text]
(2004). Rivastigmine for Parkinson Disease Dementia. JWatch General 2004: 3-3 [Full Text]
Press, D. Z. (2004). Parkinson's Disease Dementia -- A First Step?. NEJM 351: 2547-2549 [Full Text]
Miyasaki, J. M., Shannon, K., Voon, V., Ravina, B., Kleiner-Fisman, G., Anderson, K., Shulman, L. M., Gronseth, G., Weiner, W. J. (2006). Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.. Neurology 66: 996-1002 [Abstract] [Full Text]

Comments and questions? Please contact us.