Abstract Details

Title The Effects of Memantine Added to Cholinesterase Inhibitors on NPI Behavioral Domains: Pooled Post Hoc Analysis of 3 Randomized Controlled Trials in Patients With Moderate to Severe AD

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S9 - Aging and Dementia: Clinical Trials and Novel Therapies (4:47 PM-4:58 PM)

Poster/Presentation
Number 008

Background Neuropsychiatric symptoms negatively impact daily function and quality of life, hasten time to institutionalization, and increase overall healthcare costs. MEM significantly improved multiple domain scores of the NPI in patients with Alzheimer’s disease (AD) compared with placebo (PBO).

Objective To assess the effect of memantine (MEM) and a cholinesterase inhibitor (ChEI) vs ChEI alone on four syndrome domains of the Neuropsychiatric Inventory (NPI).

Design/Methods Data were pooled for participants with moderate to severe AD (baseline MMSE<20) from three, phase 3, randomized, double-blind, PBO-controlled 24-week trials (Tariot et al. JAMA, 2004; Porsteinsson et al. Alzheimer Research, 2008; Grossberg et al. CNS Drugs, 2013). The NPI has 12 items that were grouped into four syndrome domains: psychosis (agitation/aggression, hallucinations, delusions, irritability/lability), neurovegetative (aberrant motor behavior, nighttime behavior, appetite/eating change), frontal (disinhibition, euphoria/elation), and mood (anxiety, depression/dysphoria, apathy), based on previous analyses (Frisoni et al. Dement Geriatr Cogn Disord, 10:130-138, 1999). MEM/ChEI- and PBO/ChEI-treated participants were compared using an ANCOVA model estimating change from baseline at each time point.

Results Of 1262 patients, 637 were treated with MEM/ChEIs and 625 with PBO/ChEIs (age [mean±SD]: 75.7±8.3 years; baseline MMSE: 11.5±3.5; baseline NPI total score: 14.9±14.6). For all syndrome domains, mean treatment differences favored MEM/ChEIs over PBO/ChEIs. For psychosis symptoms, MEM/ChEI-treated patients improved significantly compared with PBO/ChEI-treated patients at 12 (LSMD -1.167, P<0.0001) and 24 (LSMD -1.238, P<0.0001) weeks. Similarly, neurovegetative scores were significantly improved for MEM/ChEI vs PBO/ChEI-treated patients at 12 (LSMD -0.621, P=0.0103) and 24 (LSMD -0.583, P=0.0441) weeks. For frontal and mood symptoms, no significant LSMDs were observed at 12 or 24 weeks. No analyses showed PBO/ChEI to be superior to MEM/ChEI.

Conclusions In patients with moderate to severe AD taking ChEIs, treatment with the combination of memantine and a ChEI was associated with significant benefit for psychosis and neurovegetative behavioral syndromes compared with ChEI alone.

Authors/Disclosures
Jeffrey L. Cummings, MD, FAAN PRESENTER	Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia, Actinogen, Acumen, AlphaCognition, ALZpath, Aprinoia, AriBio, Artery, Biogen, Biohaven, BioVie, BioXcel, Bristol-Myers Squib, Cassava, Cerecin, Diadem, Eisai, GAP Foundation, GemVax, Janssen, Jocasta, Karuna, Lighthouse, Lilly, Lundbeck, LSP/eqt, Mangrove Therapeutics, Merck, NervGen, New Amsterdam, Novo Nordisk, Oligomerix, ONO, Optoceutics, Otsuka, Oxford Brain Diagnostics, Prothena, ReMYND, Roche, Sage Therapeutics, Signant Health, Simcere, sinaptica, Suven, TrueBinding, Vaxxinity, and Wren pharmaceutical, assessment, and investment companies. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia, Biogen, Genentech, Grifols, Janssen, Karuna, Otsuka, reMYND, Roche, Signant Health. Dr. Cummings has stock in Artery, Vaxxinity, Behrens, Alzheon, MedAvante-Prophase, and Acumen. Dr. Cummings has received research support from NIH. Dr. Cummings has received research support from NIGMS. Dr. Cummings has received intellectual property interests from a discovery or technology relating to health care.
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 Acadia. 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 Genentech. 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 Otsuka. 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 EryDel. 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 Merck. Dr. Grossberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for acadia. 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 publishing royalties from a publication relating to health care. Dr. Grossberg has received publishing royalties from a publication relating to health care.
Anton P. Porsteinsson, MD (AD-CARE - University of Rochester School of Medicine)	Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ONO Pharmaceuticals. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Porsteinsson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IQVIA. Dr. Porsteinsson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for WebMD. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Otsuka. Dr. Porsteinsson has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Functional Neuromodulation. Dr. Porsteinsson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Xenon Pharmaceuticals. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Porsteinsson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cognitive Research Corporation. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Athira. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. The institution of Dr. Porsteinsson has received research support from Alector. The institution of Dr. Porsteinsson has received research support from Eisai. The institution of Dr. Porsteinsson has received research support from Eli Lilly. The institution of Dr. Porsteinsson has received research support from Athira. The institution of Dr. Porsteinsson has received research support from Genentech/Roche. The institution of Dr. Porsteinsson has received research support from Cassava. The institution of Dr. Porsteinsson has received research support from Vaccinex.
Suzanne Hendrix, PhD	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 stock in Pentara.
	No disclosure on file
Majid Kerolous, PharmD, MPH (Allergan)	No disclosure on file

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