Abstract
OBJECTIVE: In this post hoc analysis of a 24-week, randomized, placebo-controlled trial (MEM-MD-50, NCT00322153) of extended-release (ER) memantine (28 mg, once daily) in patients with moderate to severe Alzheimer's disease (AD) concurrently taking a cholinesterase inhibitor (placebo, n=335; memantine, n=342), we assessed the behavioral effects memantine ER as a function of patients' disease severity at Baseline, as determined using the Mini-Mental State Examination (MMSE). BACKGROUND: Because of safety risks involved with antipsychotic use in patients with AD, the use of antidementia drugs to help manage behavioral symptoms is of great interest. A new memantine ER formulation has demonstrated significant benefits compared with placebo on multiple outcome measures, including the Neuropsychiatric Inventory (NPI), a scale designed to assess behavioral symptoms in AD. DESIGN/METHODS: Patients (observed cases; N=540) were divided into 14 subgroups, corresponding to Baseline MMSE scores (range: 4-17). Baseline-to-Endpoint (Week 24) changes for memantine ER and placebo groups were assessed for each subgroup using a mixed-effects model with repeated measures, with the Baseline MMSE score as a linear covariate; sensitivity analyses were conducted using a quadratic model and a separate means model. Due to the exploratory nature of this analysis, no corrections for multiple hypothesis testing were performed. RESULTS: At Week 24, memantine ER was associated with mean improvement on the NPI over placebo across the full Baseline MMSE range of 4-17, with statistically significant (p<0.05) differences observed in the range of 7-14; outlying score ranges were limited by small n values and low statistical power. Mean between-group differences ranged from 2.7 to 3.0 points. Sensitivity analyses yielded similar results. CONCLUSIONS: In this post hoc analysis, 6 months of treatment with memantine ER in patients with moderate to severe AD was associated with significant improvement in behavioral symptoms across a wide range of Baseline severities.