Pooled Analyses on Cognitive Effects of Memantine in Patients with Moderate to Severe Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, constituting the most common cause of dementia. Memantine, an N-methyl-D-aspartate receptor antagonist indicated for the treatment of moderate to severe AD, has been shown to provide benefits in cognitive, functional, and behavioral domains in large, randomized clinical trials. The current analysis combined data from six previously published studies and assessed the effect of memantine on various cognitive functions in 1826 patients (867 on placebo and 959 on memantine) with moderate to severe AD (MMSE<20). The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) and the Severe Impairment Battery (SIB) scores from all six studies were pooled and combined into three clusters representing discrete cognitive domains: language, memory, and praxis. At baseline, there were no clinically significant differences between the memantine- and placebo-treated groups. After 24 weeks, responder analyses revealed that memantine treatment resulted in statistically significantly more patients improving on each of the three clusters, language, memory, and praxis, compared with placebo, and a lower percentage of patients treated with memantine showed any worsening on any of the three clusters compared with patients receiving placebo. It is concluded that treatment with memantine provides benefits in all three cognitive functions.