1. Memantine in Vascular Dementia Möbius H.J. and Stöffler A. International Psychogeriatrics 2003, 15 Suppl 1: 207-213

2. Analyses based on studies in patients with mild to moderate vascular dementia: Orgogozo et al. (2002) (MMM300) Wilcock et al. (2002) (MMM500) ADAS-cog analysis by severity at baseline: MMSE 20-22 MMSE 15-19 MMSE 10-14 ADAS-cog analysis by neuroradiological findings at baseline: Macrolesions, “Large Vessel Disease” No macrolesions, “Small Vessel Disease” Memantine in Vascular Dementia: Subgroup Analyses Möbius and Stöffler, Int Psychogeriatr 2003

3. Patients with “Large Vessel Disease” Hardly Show Cognitive Decline Möbius and Stöffler, Int Psychogeriatr 2003 ADAS-cog score difference -2 0 1 2 3 ADAS-cog mean change from baseline ITT, LOCF, N = 214 Improvement Worsening 01228 Memantine (20 mg/day) Placebo Week Pooled data

4. Significant Benefit of Memantine in Patients with “Small Vessel Disease” ADAS-cog score difference Möbius and Stöffler, Int Psychogeriatr 2003 * p = 0.002 versus placebo ADAS-cog mean change from baseline ITT, LOCF, N = 553 Improvement Worsening 01228 Memantine (20 mg/day) Placebo * -2 0 1 2 3 Week Pooled data

5. Largest Benefit of Memantine in More Severely Demented Patients Möbius and Stöffler, Int Psychogeriatr 2003 ADAS-cog score difference MMM500MMM300 0.32 0.53 0.95 1.35 2.43 4.12 -1.38 -0.80 0.94 0.50 0.99 4.40 Mean ADAS-cog change from baselineITT, LOCF -2 0 1 2 3 4 5 Memantine (20 mg/day) Placebo 20 - 22 15 - 19 10 - 14 MMSE at baseline Improvement Worsening

6. Summary The strongest effect of memantine on cognition was shown in the moderately demented patient population (MMSE < 15 at baseline) and in the subgroup of patients with “small vessel disease” (no macrolesions in CT/MRI) Möbius and Stöffler, Int Psychogeriatr 2003