P4-408: Early real-world clinical experience with memantine treatment for Alzheimer’s disease in the United States

Abstract

Memantine HCl, available in the U.S. only since 2004, has been shown in randomized, double–blinded, placebo–controlled clinical trials to modestly slow symptomatic progression of cognitive and functional decline in moderate to severe Alzheimer's disease (AD). However, clinical trials involve highly selected populations and rigorous compliance; the “real–world” clinical effectiveness of memantine is unknown. To perform a preliminary assessment of the clinical use and effects of memantine treatment in a U.S. memory disorders clinic. Longitudinal analysis of clinical data from the Massachusetts Alzheimer's Disease Research Center Patient Registry using linear mixed fixed and random effects modeling. 518 patients underwent serial clinical evaluations for dementia at the Massachusetts General Hospital Memory Disorders Unit: 117 were treated with memantine (± cholinesterase–inhibitor, ChEI), 160 treated with ChEI only, and 241 not treated with memantine or ChEI. At baseline subjects had/were (mean ± S.E.): age 74.6 ± 0.4 years, education 13.4 ± 0.2 years, 54% female, 95% Probable AD diagnosis, age at onset of symptoms 71.6 ± 0.4 years, Blessed Dementia–IMC score (BDS) 12.0 ± 0.3 errors, Activities of Daily Living score (ADL) 33.9 ± 0.9% dependent. Patients received memantine for a mean of 1.5 years and were followed for a mean of 2.4 years. As a group, patients not treated with memantine or ChEI deteriorated by 4.0 errors/year and 12.0% dependent/year, those taking ChEI–only deteriorated by 3.0 errors/year and 12.5% dependent/year, and those taking memantine (± ChEI) deteriorated by 2.2 errors/years and 8.5% dependent/year, on BDS and ADLs, respectively (p < 0.001 all between–group rate comparisons, except nonsignificant for ADL in no–treatment versus ChEI). Memantine was used mostly in mild to moderate AD in combination with a ChEI. Treatment with memantine and ChEI was associated with statistically significant decreases in the rates of cognitive and functional decline in the early years after treatment, beyond the benefit associated with ChEI treatment alone. This limited and preliminary analysis supports efficacy data from short–term clinical trials, but more expansive analysis of longer term data is required before reaching more definitive conclusions regarding the real–world clinical effectiveness of memantine treatment in AD.