1. Efficacy and Safety of Memantine in Patients With Mild to Moderate Vascular Dementia A Randomized, Placebo-controlled Trial (MMM 300) Orgogozo J.M., Rigaud A.S., Stöffler A., Möbius H.J., and Forette F. Stroke 2002, 33:1834-1839

2. No. of patients N = 321 DesignDouble-blind, randomized, placebo- controlled, multicenter study DiagnosisProbable VaD (acc. NINDS-AIREN, HIS  5) Age  60 (mean 76) SeverityMMSE 12 - 20 (mean 16.9) Dose; duration20 mg memantine/day; 28 weeks Primary efficacy Cognition: ADAS-cog parameters Global: CIBIC-Plus Secondary efficacy MMSE, GBS, NOSGER, CGI-C parameters Orgogozo et al., Stroke 2002 Study Design

3. Patients screened N = 403 Patients randomized N = 321 Screen failures N = 82 (20%) Completed N = 118 (76%) Withdrew N = 38 (24%) Placebo N = 156 (49%) Memantine N = 165 (51%) Completed N = 116 (70%) Withdrew N = 49 (30%) Disposition of Patients Orgogozo et al., Stroke 2002

4. ITT, LOCFADAS-cog total score Significant Benefit of Memantine on Cognition (ADAS-cog) Orgogozo et al., Stroke 2002 * p = 0.0016 versus placebo Week Worsening 19 20 21 22 23 24 01228 Memantine (20 mg/day) Placebo * ADAS-cog total score

5. Significant Benefit of Memantine on Cognition (ADAS-cog) Orgogozo et al., Stroke 2002 ITT, LOCF Mean change from baseline * p = 0.0016 versus placebo Worsening -2 0 1 2 3 * Memantine (20 mg/day) Placebo 01228 Improvement Week ADAS-cog score difference

6. Significant Benefit of Memantine on Cognition (MMSE) Orgogozo et al., Stroke 2002 TPP, N = 188MMSE analysis Week Worsening 19 18 17 16 028 Memantine (20 mg/day) Placebo * * p = 0.003 versus placebo MMSE total score

7. Good Safety and Tolerability of Memantine Adverse events in mild to moderate VaD (MMM300) MemantinePlacebo Total no. of patients165 (100%)156 (100%) Total no. of patients with AEs117 (70.9%)104 (56.7%) Agitation9 (5.5%) 11 (7.1%) Confusion8 (4.8%) 8 (5.8%) Dizziness8 (4.8%) 5 (3.2%) Bronchitis6 (3.6%) 7 (4.5%) Urinary Tract Infection5 (3.0%) 7 (4.5%) Cerebrovascular Disorder6 (3.6%) 6 (3.8%) Depression6 (3.6%) 5 (3.2%) Diarrhoea5 (3.0%) 6 (3.8%) Hypertension4 (2.4%) 7 (4.5%) Inflicted Injury5 (3.0%) 6 (3.8%) Orgogozo et al., Stroke 2002

8. Significant cognitive benefit for patients with mild to moderate vascular dementia treated with memantine compared to placebo (ADAS-cog and MMSE ) Good safety and tolerability of memantine Orgogozo et al., Stroke 2002 Summary