Abstract
Objective: To assess cognitive performance via the Severe Impairment Battery (SIB) and maintenance of improvement for memantine-ER/donepezil versus placebo/donepezil during 24-week treatment in moderate-to-severe Alzheimer’s disease (AD). Background: Memantine ER produced a significantly better outcome than placebo on co-primary endpoints of Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) and baseline-to-endpoint change on SIB in a 24-week, randomized, double-blind, placebo-controlled trial (RCT) in patients with moderate-to-severe AD concurrently taking a cholinesterase inhibitor. Design/Methods: This was a post-hoc analysis of NCT00322153 RCT observed data. Baseline-to-endpoint changes were used to classify patients based on equal scoring intervals (score changes of ≥0, ≥5, ≥10, ≥15, and ≥20). Proportions of memantine/donepezil- and placebo/donepezil-treated patients who were responders and who attained score changes at weeks 8, 12, and 18 and maintained those score changes through week 24 were compared using Fisher’s exact test. Results: 370 patients were included (187 memantine/donepezil, 183 placebo/donepezil), with baseline mean age 76.18 (SD=7.54), mean MMSE 10.92 (SD=2.73), and mean SIB total score 75.64 (SD=18.23). Compared with the placebo/donepezil group, a significantly higher percentage of patients in the memantine/donepezil-treated group achieved a score change of ≥10 (15.3% vs 27.3%, P=0.0053) or ≥15 (7.7% vs 16.6%, P=0.0105) on the SIB. The proportion of memantine/donepezil-treated patients numerically exceeded that of placebo/donepezil-treated patients at each cut-off for maintenance of response, with a significantly greater proportion maintaining a change of ≥5 (P=0.0391) and ≥10 (P=0.0283) from weeks 8–24, and a change of ≥10 and ≥15 from weeks 12–24 (P=0.0107 and 0.0349, respectively) and weeks 18–24 (P=0.0051 and 0.0100, respectively). Conclusions: Concomitant treatment with memantine ER/donepezil was associated with significant, maintained improvements over 24 weeks on the SIB than treatment with placebo/donepezil in this observed cases (OC) analysis; this favorable treatment response was particularly pronounced among patients who experienced the highest level of cognitive improvements.