To investigate the behavioral and cognitive effects of memantine in moderate to severe patients with Alzheimer disease receiving donepezil.

Study was a 24 weeks prospective, randomized, parallel group. 43 patients were enrolled in the study, 21 continued treatment with donepezil and 22 were randomized to donepezil and memantine treatment. Patients were at least 50 years old, receiving ongoing therapy with donepezil for at least 6 months (10 mg / day). Average age for both groups was 72.5 years. There were no significant imbalances between the treatment groups in demographic and baseline clinical characteristics. Cognitive, ADL, and global measures were collected at baseline and at the end of weeks 4, 8, 12, 18 and 24. Behavioral measures were obtained at baseline, at the end of week 12 and at week 24. Mean baseline MMSE scores were 15.2 for donepezil group and 14.9 for donepezil – memantine group. Mean baseline NPI scores were of 15.8 for the donepezil group and 16.4 for the donepezil – memantine group.

Patients treated with donepezil – memantine had significantly lower NPI total scores than patients treated only with donepezil. Analyses of the 12 NPI domains revealed significant effects in favor of memantine on agitation / aggression, eating / appetite, and irritability / lability. Memantine - treated patients showed significantly less deterioration in their functionality. The Severe Impairment Battery showed significant differences favoring memantine – donepezil group.

Treatment with memantine was well tolerated and reduced agitation / aggression, irritability, and appetite eating disturbances.