Abstract
Objective: To assess maintenance of response on the Severe Impairment Battery (SIB) in participants treated with memantine (MEM) in combination with a cholinesterase inhibitor (ChEI) vs placebo (PBO) with ChEI. Background: Rigorous phase 3 studies have demonstrated the efficacy of memantine (MEM) on cognitive and behavioral symptoms of Alzheimer’s disease (AD) when added to ongoing ChEI treatment. Design/Methods: Data were pooled from two phase 3, randomized, double-blind, PBO-controlled 24-week trials (Tariot et al. JAMA, 2004; Grossberg et al. CNS Drugs, 2013) evaluating MEM for patients with moderate to severe AD (baseline MMSE score<20) receiving stable ongoing ChEI treatment. SIB scores were categorized by level of improvement (≥0-, ≥5-, ≥10-point improvement from baseline) at each timepoint (weeks 4, 8, 12, 18) and were considered maintained if the patient remained in the same improvement category at all following tests through endpoint (week 24). The percentages of patients who maintained response were compared between MEM/ChEI and PBO/ChEI. Results: A significantly greater proportion of MEM/ChEI-treated patients maintained ≥5-point improvements vs PBO/ChEI from weeks 4 to 24 (P=0.0182). From weeks 8 to 24 and 12 to 24, a significantly greater proportion of MEM/ChEItreated patients maintained ≥5- and ≥10-point improvements compared with PBO/ChEI-treated patients (Pvalues< 0.01). From week 18 to 24, a significantly higher proportion of patients treated with MEM/ChEI vs PBO/ChEI maintained score improvements of ≥0 (P=0.0478), ≥5 (P=0.0137), and ≥10 (P=0.0003) points. Conclusions: The combination of MEM with a ChEI resulted in greater percentages of patients who achieved and maintained cognitive improvements over 24 weeks vs PBO/ChEI. This treatment response was particularly pronounced among patients who experienced a 5-point or greater improvement on the SIB. Treatment effects continued to emerge at week 18 and were maintained through week 24, further demonstrating SIB sensitivity and the benefit of MEM when added to ongoing ChEI treatment.