1. Memantine in Clinical Practice – Results of an Observational Study Calabrese P., Essner U. and Förstl H. Dementia and Geriatric Cognitive Disorders 2007; 24: 111-117

2. No. of patients N = 1845 Diagnosismoderate to severe Alzheimer’s disease (based on ICD-10 criteria) DesignOpen-label, multicenter, post-marketing observational study Dose; duration20 mg memantine/day; 6 months Outcome measures MMSE, NOSGER, EMD (“Explorationsmodul Demenz”) Overall clinical impression, cognition and activities of daily living (rated by physician) Safety and tolerability Study Design Calabrese et al., Dement Geriatr Cogn Disord 2007

3. Baseline Characteristics Gender, female 58.2% Mean age, years (±SD) 76.3 (± 8.7) Mean height, cm (±SD) 167.1 (± 8.1) Mean weight, kg (±SD) 70.3 (± 11.5) MMSE score, mean (±SD) 15.4 (± 5.7) Mean duration of AD, years (±SD) 2.4 (± 1.9) Memantine Calabrese et al., Dement Geriatr Cogn Disord 2007

4. Concomitant Diseases and Comedication Hypertension44.5 Heart failure 24.0 Arteriosclerosis 19.7 Other cardiac diseases 2.6 Diabetes mellitus 17.2 Other22.4 Concomitant disease% patients Calabrese et al., Dement Geriatr Cogn Disord 2007 Comedication% patients Antihypertensive drugs41.2 Antidiabetic drugs 13.4 Antidepressants 11.3 Neuroleptic drugs 9.3

5. 510152025 Significant Improvement of Mean MMSE Scores after 3 and 6 Months Baseline 3 months Mean MMSE score * * p < 0.0001 vs baseline * 6 months OC analysis Calabrese et al., Dement Geriatr Cogn Disord 2007

6. 510152025 Responder Analysis – Stabilization and Improvement under Memantine Proportion of patients (%) Calabrese et al., Dement Geriatr Cogn Disord 2007 303540 6 points improvement 3-6 points improvement 1-2 points improvement Stabilization 68.2% of patients showed improvement MMSE Score

7. Significant Improvement in All Items of the NOSGER Score Memory Instrumental Activities of Daily Living Activities of Daily Living Mood Social Behavior Disruptive Behavior 0 -0.2-0.4-0.6-1.2 -0.8 -1.4-1.6 Improvement Mean change from baseline NOSGER score difference Calabrese et al., Dement Geriatr Cogn Disord 2007 p < 0.0001 vs baseline for all items at 3 and 6 months 3 months 6 months

8. Significant Improvement in EMD Total Score (Patient and Caregiver) Area A+B Area A Area B Area C 10 98754 6 31 Improvement Mean EMD score * p < 0.0001 20 Area A+B Area A Area B Area C Patient Caregiver * Baseline 6 months Calabrese et al., Dement Geriatr Cogn Disord 2007 Area A = cognition Area B = everyday behavior and affectivity Area C = disease-related self-awareness

9. 10203040 Overall Clinical Impression: Improvement or Stabilization after 6 Months under Memantine Proportion of patients (%) Calabrese et al., Dement Geriatr Cogn Disord 2007 50 Improvement Stabilization Deterioration No answer 78.8% of patients improved or stabilized

10. Positive Effect of Memantine Treatment on Cognition and Function after 6 months of treatment Good/Very Good Moderate Poor 0 102030 40 50 Calabrese et al., Dement Geriatr Cogn Disord 2007 Cognition Daily functioning Proportion of patients (%)

11. Safety and Tolerability Restlessness0.5 Dizziness 0.4 Pneumonia 0.4 Deterioration of AD 0.4 Confusion 0.3 Cerebrovascular events0.3 Heart failure0.3 Aggression0.3 Dehydration0.3 Nausea0.2 Paranoia0.2 Agitation0.2 Urinary tract infection0.2 Adverse event% patients Calabrese et al., Dement Geriatr Cogn Disord 2007

12. Summary This study demonstrated memantine’s efficacy and safety in a real world patient population over six months of treatment Significant improvement on the MMSE Score (2.5 points on average) Improvement in memory, activities of daily living and behavior as assessed by the NOSGER These effects were also visible to the treating physician, proven by the global assessments This observational study confirms the efficacy of memantine already seen in placebo-controlled clinical studies Memantine showed an excellent safety and tolerability profile 74.4% patients had concomitant diseases with 65.4% receiving corresponding comedication None of the individual AEs occurred at a higher frequency than 0.5% These findings demonstrate the relevance of memantine’s efficacy in every day practice Calabrese et al., Dement Geriatr Cogn Disord 2007