Abstract Details

Title 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

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-007

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.

Authors/Disclosures
Frederick A. Schmitt, PhD (University of Kentucky) PRESENTER	The institution of Dr. Schmitt has received research support from NIH.
George Grossberg, MD (St Louis University School of Medicine Department of Neurology & Psychiatry)	Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome Therapeutics. Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BioXcel. Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Karuna. Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Maplight Therapeutics. Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Otsuka. Dr. Grossberg has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Takeda. The institution of Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Anavex. The institution of Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. The institution of Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Newron. The institution of Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Oligomerix. The institution of Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Quince. Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Otsuka. The institution of Dr. Grossberg has received research support from NIA. The institution of Dr. Grossberg has received research support from Functional Neuromodulation .
Pierre Tariot (Banner Alzheimer's Institute)	Pierre Tariot has received personal compensation for serving as an employee of Banner Alzheimer's Institute. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Axsome. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for WebMD. Pierre Tariot has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arcadia. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BioXcel. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cortexyme. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for eNOVA. Pierre Tariot has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Syneos. Pierre Tariot has received intellectual property interests from a discovery or technology relating to health care.
Suzanne Hendrix, PhD (Pentara)	Dr. Hendrix has received personal compensation for serving as an employee of Pentara Corporation. Dr. Hendrix has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pentara Corporation. Dr. Hendrix has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Pentara Corporation. The institution of Dr. Hendrix has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Pentara Corporation. Dr. Hendrix has or had stock in Pentara.
	No disclosure on file
Majid Kerolous, PharmD, MPH (Allergan)	No disclosure on file

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