1. Tolerability of switching from donepezil to memantine treatment in patients with moderate to severe Alzheimer’s disease (AD) Waldemar G., Hyvärinen M., Josiassen M. K., K Ø rner A., Lehto H. and Wetterberg P. International Journal of Geriatric Psychiatry 2008, 23: 979-981

2. No. of patients N = 46 (outpatients) DiagnosisProbable Alzheimer’s disease DesignDouble-blind, randomized, placebo-controlled study Age ≥ 50 years SeverityMMSE ≤ 18 Dose; duration20 mg memantine/day; 8 weeks Outcome CGI-S, MMSE, CGI-C parameters Safety and tolerability Study Design Waldemar et al., Int J Geriatr Psychiatry 2008

3. 5 mg/day Donepezil Placebo W2 Donepezil/placebo treatment stops W4W6W8 Memantine titration W1 to W3 W0W-1 Memantine 20 mg/day W4 to W8 Memantine titration W1 to W3 10 mg/day Donepezil Screening period Baseline Memantine with abrupt discontinuation of Donepezil Memantine with stepwise discontinuation of Donepezil Study Design Waldemar et al., Int J Geriatr Psychiatry 2008

4. Disposition of Patients Patients screened N = 52 Patients randomized N = 47 Withdrew N = 1 (4%) Lack of efficacy Completed N = 21 (96%) 1 withdrawal of consent MEM (stepwise) N = 22 MEM (abrupt) N = 24 Completed N = 22 (92%) Withdrew N = 2 (8%) Adverse events Screen failures N = 5 (10%) Waldemar et al., Poster presented at EFNS 2005

5. Baseline Characteristics Mean age, years (±SD)76.5 (  8.4)79.9 (  5.4) Gender, female N (%)19 (79%)18 (82%) MMSE score, mean (±SD) 13.4 (  2.7)13.0 (  3.5) CGI-S score, mean (±SD) 5.2 (  0.7)5.1 (  0.7) Abrupt Group Stepwise Group N = 24N = 22 Waldemar et al., Int J Geriatr Psychiatry 2008

6. Adverse Events Percentage (%) 50 40 30 20 10 0 Total number of patients with AEs 31.8 45.8 0 16.7 AEs in Week 1 7 patients11 patients 4 patients * Memantine (stepwise) Memantine (abrupt) * 2 Vertigo, 1 Athrosis, 1 Pruritus; none judged related to treatment Waldemar et al., Int J Geriatr Psychiatry 2008

7. Adverse Events Most frequently reported adverse events (incidence ≥ 5%) Patients with AEs11 (45.8%)7 (31.8%) Accidental injury1 (4.2%)3 (13.6%) Anxiety2 (8.3%)- Vertigo2 (8.3%)- No. of patientsN = 24 (100%)N = 22 (100%) MEM (abrupt)MEM (stepwise) Waldemar et al., Int J Geriatr Psychiatry 2008

8. Distribution of Patients by CGI Score at Week 8 40 30 20 10 0 much improved slightly improved no change slightly worse much worse % of patients 74% Improved or No ChangeWorse Memantine (stepwise) Memantine (abrupt) Waldemar et al., Poster presented at EFNS 2005

9. Summary Only 3 patients withdrew from the study (1 due to lack of efficacy, 2 due to AEs) No clinically important differences in AEs between the two groups No clinically important differences between the two groups in the incidence of potentially clinically significant vital signs or weight After the switch to memantine 74% of the patients improved or were stabilized (CGI-C)  The safety and tolerability of switching AD patients from donepezil to memantine was good with either switching schedule  After being switched to memantine the majority of the patients either remained stable or improved Waldemar et al., Int J Geriatr Psychiatry 2008