1. Why Physicians Do Not Diagnose Alzheimer’s Disease Mark A. Sager, MD Professor of Medicine and Population Health Sciences Director, Wisconsin Alzheimer’s Institute University of Wisconsin Medical School

2. WISCONSIN ALZHEIMER’S INSTITUTE Age Cognitive Function 248 Death MCI AD syndrome Normal aging Interventions

3. Diagnosing Alzheimer’s Disease Almost 50% of persons with dementia are never diagnosed or treated Most persons who are treated for dementia are treated inappropriately WISCONSIN ALZHEIMER’S INSTITUTE

4. Underrecognition of Cognitive Impairment in Assisted Living Facilities 230 ALF residents in 7 facilities in Nebraska Not dementia-specific Defined cognitive impairment as <24 on the MMSE WISCONSIN ALZHEIMER’S INSTITUTE JAGS, 2005

5. Underrecognition of Cognitive Impairment in Assisted Living Facilities WISCONSIN ALZHEIMER’S INSTITUTE 353 JAGS, 2005 MMSE < 24 MMSE ≥ 24

6. Underrecognition of Cognitive Impairment in Assisted Living Facilities WISCONSIN ALZHEIMER’S INSTITUTE 354 JAGS, 2005 No diagnosisNo treatmentSelf-medicateSurrogate decision-maker For persons with MMSE < 24 (N=145)

7. Prevalence of Undetected MCI – Study Population Mean age (yrs) 76 Female (%) 58 Education (yrs) 16 Mean MMSE 28 Source: Hermann, Sager 2002 WISCONSIN ALZHEIMER’S INSTITUTE 17

8. Prevalence of Undetected MCI N (%) Undetected dementia (n = 200)21 (11) Undetected MCI (n = 179)18 (10) Rate of undetected impairment39 (20) Source: Hermann, Sager 2002 WISCONSIN ALZHEIMER’S INSTITUTE

9. Interest in Screening and Treatment for MCI WISCONSIN ALZHEIMER’S INSTITUTE Questions from Alzheimer’s Association website “fact sheet” N= 149 71% over age 65 Dale et al JAGS, 2006

10. WISCONSIN ALZHEIMER’S INSTITUTE Would you want to be tested for memory problems as part of a routine medical exam? Yes 80 % Interest in Screening and Treatment for MCI Dale et al JAGS, 2006

11. WISCONSIN ALZHEIMER’S INSTITUTE Would you want to know as early as possible that you had Alzheimer’s Disease? Yes 92% Interest in Screening and Treatment for MCI Dale et al JAGS, 2006

12. Interest in Screening and Treatment for MCI - Conclusion WISCONSIN ALZHEIMER’S INSTITUTE “Older adults expressed high interest in screening and treatment for MCI. Such high interest is potentially troubling…” Dale et al JAGS, 2006

13. Reasons for High Rate of Undiagnosed Cases of Dementia Reliance on family Subtlety of early symptoms Low priority given by MD’s WISCONSIN ALZHEIMER’S INSTITUTE

14. Why Physicians Do Not Diagnose and Treat Alzheimer’s Disease Deficiencies in Current Knowledge Practice Obstacles Uncertainties Avoidance Behavior and Skepticism PlusCreateWhich lead to WISCONSIN ALZHEIMER’S INSTITUTE

15. Potential Benefits of Treatment with AcetylCholinesterase Inhibitors Slow cognitive decline Delay emergence of behavioral symptoms Slow functional decline Reduce caregiver stress Delay nursing home placement WISCONSIN ALZHEIMER’S INSTITUTE

16. Galantamine Long-term Cognitive Function Over 12 Months Improvement Deterioration Mean Change in ADAS-cog from Baseline Time (months) Raskind, MA, et al. Neurology 54:2261-2268; 2000. =P<0.05 Double-blindOpen-extension WISCONSIN ALZHEIMER’S INSTITUTE 58

17. Alteration of Clinical Outcomes in the Natural History of AD by Cholinesterase Inhibitors WISCONSIN ALZHEIMER’S INSTITUTE University of Pittsburgh ADRC 270 patients with AD; 135 CEI and 135 no-CEI Matched for age, education, MMSE, duration of dementia Lopez, et al., JAGS, 2005

18. WISCONSIN ALZHEIMER’S INSTITUTE Average mean change in MMSE/yr was 3.8 points ± 4.2 for 1,139 AD patients in ADRC Classified study patients as slow progressors (≤ 2 change in MMSE/yr and rapid progressors ( ≥ 3 change in MMSE/yr) Mean age 73, mean MMSE 19, mean education 12.5 years Lopez, et al., JAGS, 2005 Alteration of Clinical Outcomes in the Natural History of AD by Cholinesterase Inhibitors

19. Effect of CEI Treatment on AD Progression WISCONSIN ALZHEIMER’S INSTITUTE RR=2.45 (1.45-4.16), p=.001 Lopez et al., 2005 N=81N=82 N=54N=53 60% 40%39% 61%

20. Effect of CEI Treatment on Risk of Nursing Home Placement WISCONSIN ALZHEIMER’S INSTITUTE Lopez et al., 2005 1% 11% 50%

21. Probability of Remaining at Home Time (Days) Tacrine Dose (mg/day) s< 80 n> 80 < 120 l> 120 < 160 WISCONSIN ALZHEIMER’S INSTITUTE Knopman D, et al. Neurology 47:166-167; 1996

22. Probability of Survival Time (Days) Tacrine Dose (mg/day) s< 80 n> 80 < 120 l> 120 < 160 WISCONSIN ALZHEIMER’S INSTITUTE 91 Knopman D, et al. Neurology 47:166-167; 1996

23. WISCONSIN ALZHEIMER’S INSTITUTE Caregiver Interventions to Reduce Nursing Home Placement of Patients with AD RCT of 406 caregiver spouses, 1987-1997 New York University Required treatment group to attend support groups (58%) Allowed control group to attend support groups (42%) Neurology, 2006

24. WISCONSIN ALZHEIMER’S INSTITUTE Caregiver Interventions to Reduce Nursing Home Placement of Patients with AD Intervention Counseling sessions – family (4), individual (2) Resource and referral information, behavioral management, telephone help Weekly support groups Neurology, 2006

25. WISCONSIN ALZHEIMER’S INSTITUTE Caregiver Interventions to Reduce Nursing Home Placement of Patients with AD Results - summary Median delay in NHP = 557 days (1.5 years) Effects of intervention on NHP due to improvements in caregivers well being (tolerance, depression, satisfaction with support) Potential savings of $90,000/patient for 1.5 year delay Neurology, 2006

26. WISCONSIN ALZHEIMER’S INSTITUTE 2004 Medicaid Costs for Wisconsin NH Residents with Dementia 10,140 persons at $117 per day $455,235,120 State / County Share (40%) $182,094,120 ( In 2004, 1600 persons with dementia were served in COP,COP-W and CIP at a cost of $16.7 million)

27. Potential Long Term Care Savings of Treating Alzheimer’s Disease in Wisconsin WISCONSIN ALZHEIMER’S INSTITUTE $4.1 million Medicaid savings for delaying NH entry by 1 year for 100 persons $5.7 million personal savings for delaying NH entry by 1 year for 100 persons Source: J Alz Assoc, 2006

28. Disease Modifying Drugs in Development WISCONSIN ALZHEIMER’S INSTITUTE Tramiprosate (Azhmed) – reduces deposition of Beta amyloid Beta secretase inhibitor –reduced rate of ADL loss by 48% –reduced rate of cognitive loss by 34%

29. MMSE – Diagnostic Accuracy Abnormal (< 24) % Normal (≥ 24) % Normal0100 AD6040 Vascular5248 Mixed7129 Lewy Body7129 Frontal Lobe3169 Sensitivity – 47 Specificity - 100 WISCONSIN ALZHEIMER’S INSTITUTE

30. Clock Draw – Diagnostic Accuracy Abnormal (≤ 8) % Normal (> 8) % Normal2674 AD8713 Vascular8218 Mixed8614 Lewy Body955 Frontal Lobe7129 Sensitivity – 77 Specificity - 74 WISCONSIN ALZHEIMER’S INSTITUTE

31. Animal Fluency – Diagnostic Accuracy Sensitivity – 90 Specificity - 76 Abnormal (< 17) % Normal (> 17) % Normal2476 AD919 Vascular9010 Mixed1000 Lewy Body1000 Frontal Lobe1000 WISCONSIN ALZHEIMER’S INSTITUTE

32. Wisconsin Dementia Research Consortium Study WISCONSIN ALZHEIMER’S INSTITUTE Animal Naming Diagnostic groupAbnormal (< 14)Normal (≥ 14) Normal Cognition12%88% AD85%15% Other dementia85%15%

33. Animal Naming WISCONSIN ALZHEIMER’S INSTITUTE Introduction: “I’d like to ask a question to check your memory.” Instruction:“Tell me the names of as many animals as you can think of, as quickly as possible.” Procedure:Time for 60 seconds and record all responses. If the person stops before 60 seconds, say “Any more animals?” If the person says nothing for 15 seconds, say “A dog is an animal. Can you tell me more animals?” 1. _______________________12. _______________________ 2. _______________________13. _______________________ 3. _______________________14. _______________________ 4. _______________________15. _______________________ 5. _______________________16. _______________________ 6. _______________________17. _______________________ 7. _______________________18. _______________________ 8. _______________________19. _______________________ 9. _______________________20. _______________________ 10. _______________________21. _______________________ 11. _______________________22. _______________________ Scoring: Count the total number of animals (NOT including repetitions or non- animal words): ______________________ dog cat cow pig sheep horse lion tiger cat mouse ant spray dandelion bird

34. WISCONSIN ALZHEIMER’S INSTITUTE LOCORIATTLANGUAGECONSTMEMCALCREASONING COMPREPNAMSIMJUD †AVG. RANGE -ALERT---12-- --10-- -(S)7- --6-- -(S)6- --5-- --(S)-- --12-- --11-- --(S)-- --8-- --7-- --6-- -(S)5- --4-- --12-- --10-- -(S)4- --3 --8-- -(S)6- --5-- --6-- -(S)5- --4-- MILD MODERATE SEVERE --IMP-- --8-- --6-- --4-- --5-- --3-- --1-- --4-- --3-- --2-- --9-- --7-- --5-- --3-- --2-- --3-- --2-- --0-- --8-- --6-- --4-- --2-- --1-- --0-- --4-- --3-- --2-- --3-- --2-- --1-- Write in lower scores 1276 8510475 COGNITIVE STATUS PROFILE WAINDZ Screening Study Data Summary

35. WISCONSIN ALZHEIMER’S INSTITUTE LOCORIATTLANGUAGECONSTMEMCALCREASONING COMPREPNAMSIMJUD †AVG. RANGE -ALERT---12-- --10-- -(S)7- --6-- -(S)6- --5-- --(S)-- --12-- --11-- --(S)-- --8-- --7-- --6-- -(S)5- --4-- --12-- --10-- -(S)4- --3 --8-- -(S)6- --5-- --6-- -(S)5- --4-- MILD MODERATE SEVERE --IMP-- --8-- --6-- --4-- --5-- --3-- --1-- --4-- --3-- --2-- --9-- --7-- --5-- --3-- --2-- --3-- --2-- --0-- --8-- --6-- --4-- --2-- --1-- --0-- --4-- --3-- --2-- --3-- --2-- --1-- Write in lower scores 1276 8510475 COGNITIVE STATUS PROFILE WAIMCIZ Screening Study Data Summary

36. WISCONSIN ALZHEIMER’S INSTITUTE LOCORIATTLANGUAGECONSTMEMCALCREASONING COMPREPNAMSIMJUD †AVG. RANGE -ALERT---12-- --10-- -(S)7- --6-- -(S)6- --5-- --(S)-- --12-- --11-- --(S)-- --8-- --7-- --6-- -(S)5- --4-- --12-- --10-- -(S)4- --3 --8-- -(S)6- --5-- --6-- -(S)5- --4-- MILD MODERATE SEVERE --IMP-- --8-- --6-- --4-- --5-- --3-- --1-- --4-- --3-- --2-- --9-- --7-- --5-- --3-- --2-- --3-- --2-- --0-- --8-- --6-- --4-- --2-- --1-- --0-- --4-- --3-- --2-- --3-- --2-- --1-- Write in lower scores 1276 8510475 COGNITIVE STATUS PROFILE WAISDATZ Screening Study Data Summary

37. WISCONSIN ALZHEIMER’S INSTITUTE Animal Naming screen Adults > 65 years Diagnose and Treat Refer to Dementia Diagnostic Clinic Re-Screen at Intervals – Cognistat + Referral to MD _ + Memory Screening Process County Services and/or Alzheimer’s Association

38. Cognitive Screening Results – 8 Wisconsin Counties WISCONSIN ALZHEIMER’S INSTITUTE Persons approached1244 Persons screened1120 (90%) Persons screened positive370 (33%) (range 22%-58%) Abnormal Cognistat92%

39. Undertreatment of Alzheimer’s Disease WISCONSIN ALZHEIMER’S INSTITUTE Only 35% of persons with AD have ever been prescribed one of the standard treatments. Source: J Alz Assoc, 2006