Abstract
Background: Patients with Alzheimer's disease (AD) experience a decline in language and communication skills, which contributes significantly to caregiver stress. Memantine is an NMDA receptor antagonist approved for the treatment of moderate to severe AD. We previously reported the results of a randomized trial (MEM-MD-71; NCT00469456), which demonstrated that memantine was superior to placebo in improving functional communication in patients with moderate AD, as recognized by caregivers. This report focuses on global clinical status in patients from that trial. Methods: Native English-speaking outpatients with AD (MMSE range: 10-19) participated in a 12-week, international, double-blind, randomized study of memantine (20 mg/day; ITT n = 133) versus placebo (ITT n = 124). Concurrent cholinesterase inhibitor treatment, stable throughout the study, was permitted but not required. The primary and secondary measures were baseline-to-endpoint score changes on the FLCI and the Social Communication/Communication of Basic Needs subscales of the ASHA-FACS, which are, respectively, patient- and caregiver-based instruments designed for the assessment of functional communication abilities. An additional outcome measure was patients' global clinical status, assessed using the 7-point Clinician's Global Impression of Change (CGI-C) scale. The distributions of CGI-C scores (OC and LOCF) were compared between groups using a Cochran-Mantel-Haenszel (CMH) test. Post hoc analyses of the proportions of patients (OC and LOCF) who showed any improvement (CGI-C <4) at Week 12 and overall (i.e., throughout the trial) were performed using Generalized Estimating Equations. Results: CGI-C scores at study endpoint (Week 12; Mean ± SD) indicate a significantly better global clinical status of memantine-treated patients, compared to their placebo-treated counterparts (3.8 ± 1.1 vs. 4.0 ± 1.1, P = 0.03; both OC and LOCF). In addition, memantine treatment was associated with a greater proportion of patients who showed an overall improvement at Week 12 (39.1% vs. 28.6%, P = 0.07; OC and 39.1% vs. 28.2%, P = 0.06; LOCF) and overall (P = 0.045; OC and P = 0.04; LOCF). Conclusions: Memantine treatment of patients with moderate AD is associated with an improvement in patients' global clinical status.