Abstract
Objective: To examine the effects of memantine extended-release (ER) on Activities of Daily Living (ADLs) in patients with moderate-to-severe Alzheimer’s disease (AD). Background: In a 24-week, randomized, double-blind, placebo-controlled, parallel-group trial (NCT00322153), the efficacy of memantine ER (28 mg, once daily) on co-primary measures of cognition and global change was demonstrated in patients with moderate-to-severe AD (MMSE 3–14) concurrently taking a cholinesterase inhibitor (ChEI); treatment with adjunctive memantine ER did not achieve significance on the secondary measure of function, the 19-item Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL19). The lack of observed benefit of memantine on ADLs is in contrast to results from two pivotal memantine trials conducted in a similar patient population (MMSE 3–14 and MMSE 5–14). In those trials, monotherapy treatment with the immediate-release memantine conferred significant therapeutic benefits vs placebo on the ADCS-ADL. Design/Methods: In this post hoc analysis, the percentage of responders with ADCS-ADL19 change scores of ≤0, −2, −4, −6 and −8 were compared between treatment groups (memantine- and placebo-treated patients concurrently receiving a ChEI) using Fisher’s exact test. Results: While functional abilities declined in all patients, a greater percentage of patients treated with placebo (ChEI only) declined compared with those treated with memantine and ChEIs, with significant between-group differences observed among those with a change score of ≤-4 (20.0% placebo vs 12.1% memantine; P=0.0137), ≤-6 (13.3% vs 8.0%; P=0.0499), and ≤-8 (9.6% vs 4.9%; P=0.0453) by study end (weeks 18–24). Conclusions: This post hoc analysis suggests that the inevitable decline in function in moderate-to-severe AD patients may be ameliorated with memantine treatment compared with treatment with ChEIs alone.