A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500)

The aim of the reported trial was to investigate the safety and efficacy of memantine in mild to moderate vascular dementia (VaD). This was a 28-week, double-blind, parallel, randomized controlled trial of memantine 20 mg daily versus placebo which was conducted in 54 centres in the UK. Memantine is a uncompetitive, moderate affinity N-methyl-D-aspartate receptor antagonist. Patients with a diagnosis of probable VaD and Mini Mental State Examination total scores between 10 and 22 were eligible for inclusion. Primary efficacy parameters were the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) and the Clinical Global Impression of Change (CGI-C). A total of 579 patients were randomized and 548 patients with at least one post-baseline efficacy assessment qualified for the intent-to-treat analysis. At endpoint, memantine was shown to improve cognition relative to placebo in VaD: the change of ADAS-cog from baseline differed by a mean of -1.75 points (95% confidence intervals -3.023 to -0.49) and a median of 2 points between the two groups, while CGI-C ratings showed no significant differences between treatment groups. A total of 77% of all memantine-treated patients experienced adverse event, versus 75% of the placebo-treated patients, dizziness being the most frequent adverse event (11% versus 8%, respectively). Memantine was well tolerated and safe.