P3‐380: Effects of extended‐release memantine (28 mg, once daily) on language and communication abilities in a randomized trial of patients with moderate‐to‐severe Alzheimer's disease

Abstract

The efficacy of a new, extended-release (ER) formulation of memantine (28 mg, once daily) has been demonstrated previously in a 24-week, multinational, randomized, double-blind, placebo-controlled, parallel-group trial (MEM-MD-50, NCT00322153; placebo, n=335; memantine, n=342) in patients with moderate to severe AD concurrently taking a cholinesterase inhibitor (ChEI). The current study is a post hoc analysis, designed to explore the effects of memantine ER on face-valid groupings of language- and communication-related items from multiple outcome measures in that trial. Language items from the Severe Impairment Battery (SIB) were grouped into subscales of naming, reading/writing, and comprehension/repetition/discourse. In addition, a functional communication score was constructed using communication-related items from 2 scales administered to caregivers: the 19-item Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale (ADCS-ADL 19) and the caregiver perceived burden questionnaire (CPBQ). These items were designed to assess patients' verbal and non-verbal communication abilities, for example: “Did the subject pay attention to conversation or small talk?” (ADCS-ADL 19), or “How talkative has he/she been over the past month?” (CPBQ). For each post hoc measure, the change from baseline at week 24 was compared between groups. Analyses using observed cases (OC) and the last observation carried forward (LOCF) approach were based on an analysis of covariance (ANCOVA) model using treatment group and study center as factors and baseline value as a covariate. Analysis using the mixed-effects model with repeated measures (MMRM) utilized an unstructured covariance matrix with treatment, time, treatment by time interaction, and center as factors and baseline value as a covariate. At week 24, patients receiving memantine ER performed significantly better than patients taking placebo on the SIB subscales of Reading/Writing (OC: P=0.002; LOCF: P<0.001; MMRM: P<0.001), and Comprehension/Repetition/Discourse (OC: P=0.048; LOCF: P=0.004; MMRM: P=0.006). There was no significant difference between treatment groups on the SIB subscale of Naming (OC: P=0.093; LOCF: P=0.073; MMRM: P=0.057), or on the Functional Communication Score (OC: P=0.257; LOCF: P=0.131; MMRM: P=0.116). This post hoc analysis suggests that, in patients with moderate to severe AD receiving stable ChEI treatment, the addition of memantine ER may be associated with benefits in language abilities.