FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

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

	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 who have dementia associated with Parkinson's disease. We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients.

Methods 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.

Results 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).

Conclusions 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.

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 Tp Fakültesi, Nöroloji Anabilim Dal, 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:

• Williams-Gray, C. H., Evans, J. R., Goris, A., Foltynie, T., Ban, M., Robbins, T. W., Brayne, C., Kolachana, B. S., Weinberger, D. R., Sawcer, S. J., Barker, R. A. (2009). The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort. Brain 132: 2958-2969 [Abstract] [Full Text]  
• Olanow, C. W., Stern, M. B., Sethi, K. (2009). The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology 72: S1-S136 [Abstract] [Full Text]  
• Gill, S. S., Anderson, G. M., Fischer, H. D., Bell, C. M., Li, P., Normand, S.-L. T., Rochon, P. A. (2009). Syncope and Its Consequences in Patients With Dementia Receiving Cholinesterase Inhibitors: A Population-Based Cohort Study. Arch Intern Med 169: 867-873 [Abstract] [Full Text]  
• Grace, J, Amick, M M, Friedman, J H (2009). A double-blind comparison of galantamine hydrobromide ER and placebo in Parkinson disease. J. Neurol. Neurosurg. Psychiatry 80: 18-23 [Abstract] [Full Text]  
• PANDYA, M., KUBU, C. S., GIROUX, M. L. (2008). Parkinson disease: Not just a movement disorder. Cleveland Clinic Journal of Medicine 75: 856-864 [Abstract] [Full Text]  
• Taylor, J-P, Rowan, E N, Lett, D, O'Brien, J T, McKeith, I G, Burn, D J (2008). Poor attentional function predicts cognitive decline in patients with non-demented Parkinson's disease independent of motor phenotype. J. Neurol. Neurosurg. Psychiatry 79: 1318-1323 [Abstract] [Full Text]  
• Lee, P. H., Yong, S. W., An, Y.-S. (2008). Changes in Cerebral Glucose Metabolism in Patients with Parkinson Disease with Dementia After Cholinesterase Inhibitor Therapy. JNM 49: 2006-2011 [Abstract] [Full Text]  
• Palmqvist, S., Hansson, O., Minthon, L., Londos, E. (2008). The Usefulness of Cube Copying for Evaluating Treatment of Alzheimer's Disease. AM J ALZHEIMERS DIS OTHER DEMEN 23: 439-446 [Abstract]  
• 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.. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 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]  
• 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]  
• 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]