doi: 10.1161/01.STR.0000020094.08790.49
(Stroke. 2002;33:1834.)
© 2002 American Heart Association, Inc.
Original Contributions |
Efficacy and Safety of Memantine in Patients With Mild to Moderate Vascular Dementia
A Randomized, Placebo-Controlled Trial (MMM 300)
From CHU Pellegrin, Bordeaux, France (J.-M.O.); Hôpital Broca, Paris, France (A.-S.R., F.F.); and Merz Pharmaceuticals, Frankfurt, Germany (A.S., H.-J.M.).
Correspondence to Professor J.-M. Orgogozo, CHU Pellegrin, 33076 Bordeaux, France. E-mail j.m.orgogozo{at}neuro.u-bordeaux2.fr
Background and Purpose— Based on the hypothesis of glutamate-induced neurotoxicity (excitotoxicity) in cerebral ischemia, this study examined the efficacy and tolerability of memantine, an uncompetitive N-methyl-D-aspartate antagonist, in the treatment of mild to moderate vascular dementia.
Methods— In this multicenter, 28-week trial carried out in France, 321 patients received 10 mg/d memantine or placebo twice a day; 288 patients were valid for intent-to-treat analysis. Patients had to meet the criteria for probable vascular dementia and have a Mini-Mental State (MMSE) score between 12 and 20 at inclusion. The 2 primary end points were the cognitive subscale of the Alzheimers Disease Assessment Scale (ADAS-cog) and the global Clinician’s Interview Based Impression of Change (CIBIC-plus).
Results— After 28 weeks, the mean ADAS-cog scores were significantly improved relative to placebo. In the intention-to-treat population, the memantine group mean score had gained an average of 0.4 points, whereas the placebo group mean score had declined by 1.6 points, ie, a difference of 2.0 points (95% confidence interval, 0.49 to 3.60). The response rate for CIBIC-plus, defined as improved or stable, was 60% with memantine compared with 52% with placebo (P=0.227, intention to treat). Among the secondary efficacy parameters, which were analyzed in the per-protocol subset, MMSE was significantly improved with memantine compared with deterioration with placebo (P=0.003). The Gottfries-Brane-Steen Scale intellectual function subscore and the Nurses’ Observation Scale for Geriatric Patients disturbing behavior dimension also showed differences in favor of memantine (P=0.04 and P=0.07, respectively). Memantine was well tolerated with a frequency of adverse events comparable to placebo.
Conclusions— In patients with mild to moderate vascular dementia, memantine 20 mg/d improved cognition consistently across different cognitive scales, with at least no deterioration in global functioning and behavior. It was devoid of concerning side effects.
Key Words: cerebral ischemia • dementia • glutamate • memantine • N-methyl-D-aspartate • randomized controlled trials
This article has been cited by other articles:
 |
|
 |
|
  C. H Rojas-Fernandez and P. Moorhouse Current Concepts in Vascular Cognitive Impairment and Pharmacotherapeutic Implications Ann. Pharmacother., July 1, 2009; 43(7): 1310 - 1323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Viswanathan, W. A. Rocca, and C. Tzourio Vascular risk factors and dementia: How to move forward? Neurology, January 27, 2009; 72(4): 368 - 374. [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]
|
|
|
|
 |
|
 D S KNOPMAN Cerebrovascular disease and dementia Br. J. Radiol., December 1, 2007; 80(Special_Issue_2): S121 - S127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. V. Bowler Modern concept of vascular cognitive impairment Br. Med. Bull., September 1, 2007; 83(1): 291 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 References PsychiatryOnline CME, May 1, 2007; 2007(1): 2 - 2. [Full Text]
|
|
|
|
 |
|
 R. R. Patel and M. P. Mehta Targeted Therapy for Brain Metastases: Improving the Therapeutic Ratio Clin. Cancer Res., March 15, 2007; 13(6): 1675 - 1683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lexchin Different conclusions about memantine Can Fam Physician, March 1, 2007; 53(3): 403 - 404. [Full Text] [PDF]
|
|
|
|
|
|
F. Massoud Maladie d'Alzheimer Can Fam Physician, January 1, 2007; 53(1): 50 - 54. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 D. Khuntia, P. Brown, J. Li, and M. P. Mehta Whole-Brain Radiotherapy in the Management of Brain Metastasis J. Clin. Oncol., March 10, 2006; 24(8): 1295 - 1304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Knopman Dementia and Cerebrovascular Disease Mayo Clin. Proc., February 1, 2006; 81(2): 223 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Reisberg, R. Doody, A. Stoffler, F. Schmitt, S. Ferris, and H. J. Mobius A 24-Week Open-Label Extension Study of Memantine in Moderate to Severe Alzheimer Disease Arch Neurol, January 1, 2006; 63(1): 49 - 54. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B Sleeper Antipsychotic Dose-Sparing Effect with Addition of Memantine Ann. Pharmacother., September 1, 2005; 39(9): 1573 - 1576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Molinuevo, A. Llado, and L. Rami Memantine: Targeting glutamate excitotoxicity in Alzheimer's disease and other dementias American Journal of Alzheimer's Disease and Other Dementias, March 1, 2005; 20(2): 77 - 85. [Abstract] [PDF]
|
|
|
|
 |
|
 K. M. Langa, N. L. Foster, and E. B. Larson Mixed Dementia: Emerging Concepts and Therapeutic Implications JAMA, December 15, 2004; 292(23): 2901 - 2908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. A. Hare, E. WoldeMussie, R. K. Lai, H. Ton, G. Ruiz, T. Chun, and L. Wheeler Efficacy and Safety of Memantine Treatment for Reduction of Changes Associated with Experimental Glaucoma in Monkey, I: Functional Measures Invest. Ophthalmol. Vis. Sci., August 1, 2004; 45(8): 2625 - 2639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. A. Ajilore and A. Kumar Delirium and Dementia Focus, April 1, 2004; 2(2): 210 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Erkinjuntti, G. Roman, S. Gauthier, H. Feldman, and K. Rockwood Emerging Therapies for Vascular Dementia and Vascular Cognitive Impairment Stroke, April 1, 2004; 35(4): 1010 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. V. Bowler Vascular Cognitive Impairment Stroke, February 1, 2004; 35(2): 386 - 388. [Full Text] [PDF]
|
|
|
|
|
|
P. N. Tariot, M. R. Farlow, G. T. Grossberg, S. M. Graham, S. McDonald, and I. Gergel Memantine Treatment in Patients With Moderate to Severe Alzheimer Disease Already Receiving Donepezil: A Randomized Controlled Trial JAMA, January 21, 2004; 291(3): 317 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Molinuevo, V. Garcia-Gil, and A. Villar Memantine: An antiglutamatergic option for dementia American Journal of Alzheimer's Disease and Other Dementias, January 1, 2004; 19(1): 10 - 18. [Abstract] [PDF]
|
|
|
|
 |
|
 {blacktriangledown}Memantine for dementia? DTB, October 1, 2003; 41(10): 73 - 76. [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]
|
|
|
|
|
|
R. M. Bonelli Editorial Comment--How to Treat Vascular Dementia? Stroke, October 1, 2003; 34(10): 2331 - 2332. [Full Text] [PDF]
|
|
|
|
|
|
August 26 Highlights Neurology, August 26, 2003; 61(4): 429 - 429. [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]
|
|
|
|
|
|
J. V. Bowler Acetylcholinesterase Inhibitors for Vascular Dementia and Alzheimer's Disease Combined With Cerebrovascular Disease Stroke, February 1, 2003; 34(2): 584 - 586. [Full Text] [PDF]
|
|