| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Karolinska Institutet, Alzheimer’s Disease Research Center, Division of Geriatric Medicine (Dr. Winblad), Huddinge Hospital B, Stockholm, Sweden; the Department of Geriatric Medicine (Dr. Engedal), Ullevaal University Hospital, Oslo, Norway; the Department of Neurology (Dr. Soininen), University and University Hospital of Kuopio, Kuopio, Finland; the Department of Psychiatry (Dr. Verhey), University Hospital of Maastricht, Institute of Brain and Behaviour, Maastricht, The Netherlands; The Neuroscience Center, Department of Neurology (Dr. Waldemar), Rigshospitalet, University Hospital, Copenhagen, Denmark; the Department of Family Medicine (Dr. Wimo), Umeå University, Umeå, Sweden; Pfizer AB (A.-L. Wetterholm and A. Haglund), Taby, Sweden; and Pfizer Pharmaceuticals Group (Drs. Zhang and Subbiah), Pfizer, Inc., New York, NY.
Address correspondence and reprint requests to Dr. Bengt Winblad, Karolinska Institutet, Alzheimer’s Disease Research Center, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research, Division of Geriatric Medicine, Huddinge Hospital B 84, 14186 Stockholm, Sweden; e-mail: Bengt.Winblad{at}neurotec.ki.se
Objective:— To evaluate the long-term clinical efficacy and safety of donepezil versus placebo over 1 year in patients with mild to moderate AD.
Methods:— Patients (n = 286; mean age, 72.5 years) with possible or probable AD from five Northern European countries were randomized to receive either donepezil (n = 142; 5 mg/day for 28 days, followed by 10 mg/day) or placebo (n = 144) for 1 year.
Results:— The study was completed by 66.9% of the donepezil- and 67.4% of the placebo-treated patients. The benefit of donepezil over placebo was demonstrated by the Gottfries-Bråne-Steen (a global assessment for rating dementia symptoms) total score at weeks 24, 36, and 52 (p < 0.05) and at the study end point (week 52, last observation carried forward; p = 0.054). Advantages of donepezil over placebo were also observed in cognition and activities of daily living (ADL) assessed by the Mini-Mental State Examination at weeks 24, 36, and 52, and the end point (p < 0.02) and by the Progressive Deterioration Scale at week 52 and the end point (p < 0.05). Adverse events (AE) were recorded for 81.7% of donepezil- and 75.7% of placebo-treated patients, with 7% of donepezil- and 6.3% of placebo-treated patients discontinuing because of AE. Treatment response to donepezil was not predicted by APOE genotype or sex in this population.
Conclusion:— As the first 1-year, multinational, double-blinded, placebo-controlled study of a cholinesterase inhibitor in AD, these data support donepezil as a well tolerated and effective long-term treatment for patients with AD, with benefits over placebo on global assessment, cognition, and ADL.
This article has been cited by other articles:
|
|
 |
|
  Jay Cheol Kwon, Eung Gyu Kim, Jae Woo Kim, Oh Dae Kwon, Bong Goo Yoo, Hyon Ah Yi, Nack Cheon Choi, Seon Young Ahn, Byung Hwa Lee, Myong Jin Kang, et al. A Multicenter, Open-Label, 24-Week Follow-Up Study for Efficacy on Cognitive Function of Donepezil in Binswanger-Type Subcortical Vascular Dementia American Journal of Alzheimer's Disease and Other Dementias, August 1, 2009; 24(4): 293 - 301. [Abstract] [PDF]
|
|
|
|
 |
|
 D. A. Smith Treatment of Alzheimer's disease in the long-term-care setting Am. J. Health Syst. Pharm., May 15, 2009; 66(10): 899 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Doody, S. H. Ferris, S. Salloway, Y. Sun, R. Goldman, W. E. Watkins, Y. Xu, and A. K. Murthy Donepezil treatment of patients with MCI: A 48-week randomized, placebo-controlled trial Neurology, May 5, 2009; 72(18): 1555 - 1561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Sevigny, J. M. Ryan, C. H. van Dyck, Y. Peng, C. R. Lines, M. L. Nessly, and On behalf of the MK-677 Protocol 30 Study Group Growth hormone secretagogue MK-677: No clinical effect on AD progression in a randomized trial Neurology, November 18, 2008; 71(21): 1702 - 1708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Hogan MD, P. Bailey MD, S. Black MD, A. Carswell MSc PhD, H. Chertkow MD, B. Clarke MD, C. Cohen BA MD, J. D. Fisk PhD, D. Forbes RN PhD, M. Man-Son-Hing MSc MD, et al. Diagnosis and treatment of dementia: 5. Nonpharmacologic and pharmacologic therapy for mild to moderate dementia Can. Med. Assoc. J., November 4, 2008; 179(10): 1019 - 1026. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Qaseem, V. Snow, J. T. Cross Jr., M. A. Forciea, R. Hopkins Jr., P. Shekelle, A. Adelman, D. Mehr, K. Schellhase, D. Campos-Outcalt, et al. 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, March 4, 2008; 148(5): 370 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Raina, P. Santaguida, A. Ismaila, C. Patterson, D. Cowan, M. Levine, L. Booker, and M. Oremus Effectiveness of Cholinesterase Inhibitors and Memantine for Treating Dementia: Evidence Review for a Clinical Practice Guideline Ann Intern Med, March 4, 2008; 148(5): 379 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A D Hutchinson and J L Mathias Neuropsychological deficits in frontotemporal dementia and Alzheimer's disease: a meta-analytic review J. Neurol. Neurosurg. Psychiatry, September 1, 2007; 78(9): 917 - 928. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Rowland, J. Rigby, A. C. Harper, and R. Rowland Cardiovascular monitoring with acetylcholinesterase inhibitors: a clinical protocol Adv. Psychiatr. Treat., May 1, 2007; 13(3): 178 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Chiappelli, A. M. Navarro, D. R. Moradi, E. Manfrini, and P. Prolo Evidence-Based Research in Complementary and Alternative Medicine III: Treatment of Patients with Alzheimer's Disease Evid. Based Complement. Altern. Med., December 1, 2006; 3(4): 411 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Burns and J. O'Brien Clinical practice with anti-dementia drugs: a consensus statement from British Association for Psychopharmacology J Psychopharmacol, November 1, 2006; 20(6): 732 - 755. [Abstract] [PDF]
|
|
|
|
 |
|
 H.-W. Klafki, M. Staufenbiel, J. Kornhuber, and J. Wiltfang Therapeutic approaches to Alzheimer's disease Brain, November 1, 2006; 129(11): 2840 - 2855. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hedgecoe Pharmacogenetics as Alien Science: Alzheimer's Disease, Core Sets and Expectations Social Studies of Science, October 1, 2006; 36(5): 723 - 752. [Abstract] [PDF]
|
|
|
|
 |
|
 M. R. Farlow Use of Antidementia Agents in Vascular Dementia: Beyond Alzheimer Disease Mayo Clin. Proc., October 1, 2006; 81(10): 1350 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lopez-Pousa, J. G. Olmo, J. V. Franch, A. T. Estrada, O. S. Cors, I. P. Nierga, and E. Gelada-Batlle Comparative analysis of mortality in patients with Alzheimer's disease treated with donepezil or galantamine. Age Ageing, July 1, 2006; 35(4): 365 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Maurice, J. Meunier, B. Feng, J. Ieni, and D. T. Monaghan Interaction with {sigma}1 Protein, but Not N-Methyl-D-aspartate Receptor, Is Involved in the Pharmacological Activity of Donepezil J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 606 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V Jelic, M Kivipelto, and B Winblad Clinical trials in mild cognitive impairment: lessons for the future J. Neurol. Neurosurg. Psychiatry, April 1, 2006; 77(4): 429 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Marseille and D. H.S. Silverman Recognition and treatment of Alzheimer's disease: A case-based review American Journal of Alzheimer's Disease and Other Dementias, March 1, 2006; 21(2): 119 - 125. [Abstract] [PDF]
|
|
|
|
|
|
C. M. Hernandez, D. A. Gearhart, V. Parikh, E. J. Hohnadel, L. W. Davis, M. L. Middlemore, S. P. Warsi, J. L. Waller, and A. V. Terry Jr Comparison of Galantamine and Donepezil for Effects on Nerve Growth Factor, Cholinergic Markers, and Memory Performance in Aged Rats J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 679 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kaduszkiewicz, T. Zimmermann, H.-P. Beck-Bornholdt, and H. van den Bussche Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials BMJ, August 6, 2005; 331(7512): 321 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hashimoto, H. Kazui, K. Matsumoto, Y. Nakano, M. Yasuda, and E. Mori Does Donepezil Treatment Slow the Progression of Hippocampal Atrophy in Patients With Alzheimer's Disease? Am J Psychiatry, April 1, 2005; 162(4): 676 - 682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P J Connelly, N P Prentice, and K G Fowler Predicting the outcome of cholinesterase inhibitor treatment in Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, March 1, 2005; 76(3): 320 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Ellis Cholinesterase Inhibitors in the Treatment of Dementia J Am Osteopath Assoc, March 1, 2005; 105(3): 145 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Budson and B. H. Price Memory Dysfunction N. Engl. J. Med., February 17, 2005; 352(7): 692 - 699. [Full Text] [PDF]
|
|
|
|
 |
|
 J. M Holroyd-Leduc Long term donepezil did not delay institutionalisation or progression to disability in patients with Alzheimer's disease Evid. Based Med., February 1, 2005; 10(1): 15 - 15. [Full Text] [PDF]
|
|
|
|
|
|
S. Salloway, S. Ferris, A. Kluger, R. Goldman, T. Griesing, D. Kumar, and S. Richardson Efficacy of donepezil in mild cognitive impairment: A randomized placebo-controlled trial Neurology, August 24, 2004; 63(4): 651 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Herrmann and D. Knopman Donepezil therapy for neuropsychiatric symptoms in AD: Methods make the message Neurology, July 27, 2004; 63(2): 200 - 201. [Full Text] [PDF]
|
|
|
|
|
|
J. L. Cummings Alzheimer's Disease N. Engl. J. Med., July 1, 2004; 351(1): 56 - 67. [Full Text] [PDF]
|
|
|
|
|
|
K Rockwood Size of the treatment effect on cognition of cholinesterase inhibition in Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, May 1, 2004; 75(5): 677 - 685. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Black, G. C. Roman, D. S. Geldmacher, S. Salloway, J. Hecker, A. Burns, C. Perdomo, D. Kumar, and R. Pratt Efficacy and Tolerability of Donepezil in Vascular Dementia: Positive Results of a 24-Week, Multicenter, International, Randomized, Placebo-Controlled Clinical Trial Stroke, October 1, 2003; 34(10): 2323 - 2330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Lanctot, N. Herrmann, K. K. Yau, L. R. Khan, B. A. Liu, M. M. LouLou, and T. R. Einarson Efficacy and safety of cholinesterase inhibitors in Alzheimer's disease: a meta-analysis Can. Med. Assoc. J., September 16, 2003; 169(6): 557 - 564. [Abstract] [Full Text]
|
|
|
|
|
|
C. H. Kawas Early Alzheimer's Disease N. Engl. J. Med., September 11, 2003; 349(11): 1056 - 1063. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Adachi, S. Kawakatsu, T. Hosoya, K. Otani, T. Honma, A. Shibata, and Y. Sugai Morphology of the Inner Structure of the Hippocampal Formation in Alzheimer Disease AJNR Am. J. Neuroradiol., September 1, 2003; 24(8): 1575 - 1581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wilkinson, R. Doody, R. Helme, K. Taubman, J. Mintzer, A. Kertesz, and R.D. Pratt Donepezil in vascular dementia: A randomized, placebo-controlled study Neurology, August 26, 2003; 61(4): 479 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Boustani, B. Peterson, L. Hanson, R. Harris, and K. N. Lohr Screening for Dementia in Primary Care: A Summary of the Evidence for the U.S. Preventive Services Task Force Ann Intern Med, June 3, 2003; 138(11): 927 - 937. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Brangman Long-term cholinesterase inhibitor therapy for Alzheimer's disease: Implications for long-term care American Journal of Alzheimer's Disease and Other Dementias, March 1, 2003; 18(2): 79 - 84. [Abstract] [PDF]
|
|
|
|
 |
|
 N.-H. Trinh, J. Hoblyn, S. Mohanty, and K. Yaffe Efficacy of Cholinesterase Inhibitors in the Treatment of Neuropsychiatric Symptoms and Functional Impairment in Alzheimer Disease: A Meta-analysis JAMA, January 8, 2003; 289(2): 210 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K Rockwood, J E Graham, and S Fay Goal setting and attainment in Alzheimer's disease patients treated with donepezil J. Neurol. Neurosurg. Psychiatry, November 1, 2002; 73(5): 500 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Nobili, M. Koulibaly, P. Vitali, O. Migneco, G. Mariani, K. Ebmeier, A. Pupi, P. H. Robert, G. Rodriguez, and J. Darcourt Brain Perfusion Follow-Up in Alzheimer's Patients During Treatment with Acetylcholinesterase Inhibitors J. Nucl. Med., August 1, 2002; 43(8): 983 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Deleu, B. Winblad, G. Waldemar, A. Wimo, P. Subbiah, and R. Zhang A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD Neurology, March 12, 2002; 58(5): 835 - 836. [Full Text] [PDF]
|
|
|
|
|
|
O L Lopez, J T Becker, S Wisniewski, J Saxton, D I Kaufer, and S T DeKosky Cholinesterase inhibitor treatment alters the natural history of Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, March 1, 2002; 72(3): 310 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gauthier Advances in the pharmacotherapy of Alzheimer's disease Can. Med. Assoc. J., March 1, 2002; 166(5): 616 - 623. [Full Text] [PDF]
|
|
Read all Correspondence
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
