Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300).
OBJECTIVE
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.
Orgogozo
Jean-Marc
JM
CHU Pellegrin, Bordeaux, France. j.m.orgogozo@neuro.u-bordeaux2.fr
Rigaud
Anne-Sophie
AS
Stöffler
Albrecht
A
Möbius
Hans-Jorgen
HJ
Forette
Françoise
F
D000368:Aged; D003071:Cognition / Q000187:drug effects; D015140:Dementia, Vascular / Q000188:drug therapy*; D018450:Disease Progression; D004244:Dizziness / Q000209:etiology; D015259:Dopamine Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008559:Memantine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009483:Neuropsychological Tests; D016896:Treatment Outcome
D015259:Dopamine Agents; D016202:N-Methylaspartate; D008559:Memantine