Objective: The primary aim of this study was to assess the long-term safety and efficacy of memantine in patients with moderate to severe Alzheimer's disease. A growing body of data suggests that changes in glutamatergic activity in the brain play an important pathophysiologic role in Alzheimer's disease (AD). Thus, agents that antagonize the excitotoxic effects of glutamate hold promise for the treatment of AD. One such agent is memantine, a moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist.
Design/Methods: We previously conducted a 28-week, randomized, double-blind, placebo-controlled study of memantine in 252 patients with moderate to severe AD (Global Deterioration Scale [GDS] Stages 5 and 6, Functional Assessment Staging [FAST] scores ³6a, MMSE range 3-14). At the end of double-blind treatment, patients randomized to memantine exhibited significantly less functional and cognitive decline (p<0.05) than patients treated with placebo, as measured by the ADCS Activities of Daily Living (ADCS-ADL), modified for moderate to severe AD, FAST, and the Severe Impairment Battery (SIB), respectively. In the present study, 175 patients who completed the 28-week double-blind study were given open-label memantine treatment for an additional 24 weeks. Raters remained blind as to the patients' initial study treatment. Efficacy parameters included the Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC-Plus), ADCS-ADL, FAST, and SIB.
Results: Following 24 weeks of open-label treatment, the results observed for each of these efficacy measures demonstrated that patients who switched to memantine from placebo improved relative to the projected rate of continued decline. In addition, there were no clinically important differences in adverse events between patients switched to memantine or maintained on memantine during the extension phase, suggesting that maintenance memantine therapy was well tolerated.
Conclusion: Overall efficacy and safety findings support the use of memantine in long-term treatment of patients with moderate to severe AD.
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