Abstract
Background: Agitation is a common neuropsychiatric comorbidity associated with Alzheimer’s disease (AD) that can increase caregiver burden. The MEM-MD-50 trial demonstrated the behavioral benefits of treatment with extended-release memantine (MemER) in moderate to severe AD patients receiving a cholinesterase inhibitor (ChEI). This post hoc analysis aimed to examine the effects of treatment with MemER+ChEI vs placebo+ChEI on agitation among trial participants with agitation at either baseline or end of treatment. Methods: Patients with moderate to severe AD were randomized to MemER+ChEI or placebo+ChEI treatment in the double-blind MEM-MD-50 study (NCT00322153) for 24 weeks. Least squares mean differences (LSMD) between groups in change from baseline to Weeks 12 and 24 for the Neuropsychiatric Inventory (NPI) total score, Caregiver Distress (NPI-D) total score, and individual item scores were analyzed among participants with a score at either baseline or endpoint >0 for each respective variable, using an analysis of covariance (ANCOVA; α=0.05). Results: A total of 593 participants were included in the analysis, 291 treated with MemER+ChEI and 302 treated with placebo+ChEI. A total of 280 (96.2%) and 291 (96.4%) of those subjects had NPI total scores >0 at baseline or endpoint; 151 (51.9%) and 148 (49.0%) participants, respectively, had NPI-agitation item scores >0 at baseline or endpoint. At Week 12, the LSMD were significant in favor of MemER+ChEI for the NPI total score (-1.89, P<0.05), NPI-Agitation (-0.72, P<0.05), NPI-D total (-0.92, P=0.07), and for NPI-D-Agitation (-0.50, P<0.05). At Week 24, the LSMD for NPI total score was -3.21 (P<0.01), -1.29 for NPI-Agitation (P<0.01), -1.12 for NPI-D total score (P=0.07), and -0.63 for NPI-D-Agitation (P<0.05). Other items with significant between-group differences in LSMD at Week 12 included NPI-Aberrant Motor Behavior, NPI-Delusion, and NPI-D-Delusion; at Week 24, significant between-group differences were also observed for NPI-Delusion, and NPI-Nighttime Behavior (all in favor of MemER+ChEI treatment). Conclusions: This post hoc analysis suggests that the addition of MemER to ChEI treatment may reduce agitation in moderate to severe AD patients, and may also reduce the caregiver burden associated with agitation.