Efficacy of Memantine Added to Cholinesterase Inhibitors on SIB Higher-Order Cognitive Domains: Pooled Post Hoc Analysis of 2 Randomized Controlled Trials in Patients With Moderate to Severe AD (P4.1-007)
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Abstract
Objective: To evaluate the effect of the combination of memantine (MEM) with a cholinesterase inhibitor (ChEI) vs placebo (PBO) with ChEI on total Severe Impairment Battery (SIB) and three higher-order cognitive domains (memory, language, and praxis).
Background: The SIB is used to assess cognitive changes in patients with Alzheimer’s disease (AD), allowing for reliable, valid, and sensitive detection of treatment effects when floor effects may be present on other cognitive tests. MEM results in significant improvements on the SIB compared with PBO in moderate to severe AD patients treated concurrently with a ChEI.
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) in patients with moderate to severe AD (baseline MMSE score<20). The SIB was administered at baseline and weeks 4, 8, 12, 18, and 24. Based on Schmitt et al. Alzheimer Dis Assoc Disord, 2006, SIB domains were aggregated to create higher-order subscales of memory (memory, attention, orientation, orienting to name), language (language, social interaction), and praxis (praxis, visuospatial ability, construction).
Results: Compared with PBO/ChEI, MEM/ChEI significantly improved total SIB scores at weeks 8, 12, 18, and 24 (all, P<0.05). An analysis of higher-order domains demonstrated that MEM/ChEI treatment conferred significant effects on memory and language vs PBO/ChEI at weeks 12, 18, and 24 (all, P<0.05). On the higher-order domain of praxis, MEM/ChEI showed significant effects vs PBO/ChEI at all timepoints (weeks 4, 8, 12, 18, and 24, all P<0.05).
Conclusions: The combination of MEM with a ChEI produced early and consistent improvements in cognition for patients with moderate to severe AD. Analysis of higher-order domains on the SIB further supported the efficacy of MEM in maintaining key cognitive functions (memory, language, and praxis), even when these patients are receiving the standard of ongoing ChEI treatment.
Disclosure: Dr. Schmitt has received research support from NIH. Dr. Grossberg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acadia, Alkahest, Allergan, Inc., Avanir Pharmaceuticals, Axovant, GE, Genetech, Inc., Lundbeck Research USA, Inc., Novartis, Otsuka, Roche Diagnostics Corporation, Takeda Pharmaceutical Company, EryDel, Merck & Co., Inc., and Newron. Dr. Grossberg has received research support from Cognoptix, Genentech, Inc., Janssen Pharmaceutica, Roche Diagnostics Corporation, and NIH. Dr. Tariot has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, AC Immune, Acadia, Auspex, Boehringer Ingelheim, Chase Pharmaceuticals, Corium, Eisai, GliaCure, INSYS Therapeutics, Pfizer, T3D, AstraZeneca, Avanir, Biogen, Brian Test, Inc., Cognoptix, Eli Lilly, H. Lundbeck A/S, Merck and Company, and Roche. Dr. Tariot has received royalty, license fees, or contractual rights payments from the University of Rochester. Dr. Tariot holds stock and/or stock options in Adamas. Dr. Tariot has received research support from AstraZeneca, Avanir, Biogen, Brian Test, Inc., Cognoptix, Eli Lilly, H. Lundbeck A/S, Merck and Company, Roche, Amgen, Avid, Functional Neuromodulation, GE Healthcare, Genentech, Novartis, Takeda, Targacept, the National Institute on Aging, and the Arizona Department of Health Services.. Dr. Hendrix has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pentara Corporation, a consulting company that received funding from Allergan plc and consults for several other pharmaceutical companies.. Dr. Ellison has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pentara Corporation. Dr. Kerolous has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan.
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