1. How Is Your Memory? Evaluating Memory in the Individual and Its Relationship to Alzheimer's Disease J. Wesson Ashford, M.D., Ph.D. Clinical Professor (affiliated) Psychiatry & Behavioral Sciences, Stanford University Senior Research Scientist Stanford/VA Aging Clinical Research Center, VA Palo Alto Health Care System Palo Alto, California

2. Dementia Definition   Multiple Cognitive Deficits:   Memory dysfunction   especially new learning, a prominent early symptom   At least one additional cognitive deficit aphasia, apraxia, agnosia, or executive dysfunction   Cognitive Disturbances:   Sufficiently severe to cause impairment of occupational or social functioning and   Must represent a decline from a previous level of functioning

3. Alzheimer’s Disease   First described by Alois Alzheimer, a German neuropathologist, in 1907   Observed in a 51-year-old female patient with paranoia, memory loss, disorientation, and hallucinations   Postmortem studies characterized senile plaques and neurofibrillary tangles (NFTs) in the cerebral cortex   Senile plaques: Extracellular accumulation of insoluble fragments of beta-amyloid (A  1-42 )   NFTs: Intracellular accumulation of hyperphosphorylated tau strands

4. Need for Mass Screening   Alzheimer’s disease, dementia, and memory problems are difficult to detect when they are mild   about 90% missed early   about 25% are still missed late   There are important accommodations and interventions that should be made when there are cognitive impairments   (like needing glasses or having driving restrictions if you have vision problems)

5. Audience Screening   Presentation of complex pictures (that are easily remembered normally) are useful for detecting memory difficulties   Testing memory using a pictures approach needs standardization for population use   Picture memory is less affected by education   Picture memory can be tested by computer   Audiences can be shown slide presentations

6. BEGINNING INSTRUCTIONS 1) 1) Open the booklet 2) 2) Read the Screening for Memory Problems Information Sheet 3) 3) Fill out the Demographic Information sheet 4) 4) Turn over the Demographic Information sheet and read the instructions under for the Answer Sheet for Memory Screening

7. Screening for Memory Problems Information Sheet IRB FORM (exempt)   Description: You are invited to participate in a research study of memory and aging. You will take a memory test that involves looking at a number of pictures and indicating which are duplicated. You may also be asked to remember a list of words, or to take other brief memory tests. If the results of these tests indicate that you may have some memory concerns, we may offer you the opportunity to participate in more detailed memory studies.   For Questions About This Study: If you have any questions about this study, please contact: Dr. Wes Ashford, Aging Clinical Research Center, 3801 Miranda Avenue (151Y), VA Palo Alto Health Care System, Palo Alto, CA 94304, (650) 852-3287.   Purpose: This is a research program to screen for memory problems. Information we collect about you will be added to information about other people and analyzed to help researchers and clinicians better understand how memory changes with aging. The results of this research study may be presented at scientific or medical meetings or published in scientific journals. However, personal information or your identity will not be disclosed. Your participation in this research study will take approximately 30 minutes to one hour.   Participation is Voluntary: If you have read this form and have decided to participate in this project, please understand your participation is voluntary and you have the right to withdraw your consent or discontinue participation at any time without penalty or loss of benefits to which you are otherwise entitled. You have the right to refuse to answer particular questions. Your individual privacy will be maintained in all published and written data resulting from the study.   Independent Contact: If you are not satisfied with the manner in which this study is being conducted, or if you have any concerns, complaints, or general questions about the research or your rights as a research study subject, please contact the Stanford Institutional Review Board (IRB) to speak to an informed individual who is independent of the research team at (650)-723-5244 or toll free at 1-866-680-2906. Or write the Stanford IRB, Administrative Panels Office, Stanford University, Stanford, CA 94305-5401.

8. Demographic Information (front of sheet) (circle, check, or fill in answers) Month of Birth: Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Year of Birth: 19 _____ ____ Gender:Male __________ Female__________ Education Level (number of years): ________ 1 Elementary (0-6)2 Jr. High School (7-8) 3 High School (12) 4 Some College (13-15) 5 AA Degree (14)6 Bachelors Degree (16) 7 Masters Degree (18)8 PhD, MD, JD (20+)9 Other or unknown Veteran Status: Vet_____ NonVet______ Unknown_____ Occupation: _______ 1 Never employed2 Student3 Homemaker 4 Unskilled/semiskilled 5 Skilled trade/craft6 Clerical/office Worker 7 Manager Business/Gov8 Professional/Technical9 Other or Unknown Employment Status: Full Time____ Part Time____ Unemployed____ Retired____ Primary Race: __________ 1 White2 Black or African American 3 American Indian or Native Alaskan4 Native Hawaiian or other Pacific Islander 5 North Asian (i.e., China, Japan)6 Middle East/South Asian 7 More than one race8 Decline to state 9 Unknown Hispanic Ethnic Background? No____ Yes____ Unknown____ Have you had problems with your memory recently? Yes_______ No__________

9. Answer Sheet for Memory Screening (back of sheet) Carefully look at each picture. If you see a picture that you have seen before, mark the circle next to the number of the repeat picture. For the main test, you will see 50 pictures. Each picture is numbered. The pictures will stay on the screen for 5 seconds. 25 pictures are new, 25 pictures are repeated.

10. MemTrax Memory GAME   50 pictures will be shown (there are 10 practice pictures that will be shown first).   When you see a picture for the first time, look at it carefully and try to remember it.   If you recognize a picture that you have seen before, then look at the number and fill in the circle next to that number. 1 O =>> 1  1

11. 1

12. 2

13. 3

14. 4

15. 5

16. 6

17. 7

18. 8

19. 9

20. 10

21. Practice Test: (circles should be marked for repeats) 1 O (New) 2 O (New) 3 O(New) 4  (Repeat) 5 O (New) 6  (Repeat) 7 O(New) 8  (Repeat) 9  (Repeat) 10  (Repeat)

22. 1

23. 2

24. 3

25. 4

26. 5

27. 6

28. 7

29. 8

30. 9

31. 10

32. 11

33. 12

34. 13

35. 14

36. 15

37. 16

38. 17

39. 18

40. 19

41. 20

42. 21

43. 22

44. 23

45. 24

46. 25

47. 26

48. 27

49. 28

50. 29

51. 30

52. 31

53. 32

54. 33

55. 34

56. 35

57. 36

58. 37

59. 38

60. 39

61. 40

62. 41

63. 42

64. 43

65. 44

66. 45

67. 46

68. 47

69. 48

70. 49

71. 50

72. THE END Please note the number on your answer sheet, then hand it in.

73. MEMTRAX Memory Test 116 subjects – mostly elderly normals, some young, some dementia patients False positive errors (false recognition) – 33(64);6(58);47(27)—4,18,23,34(1);1,2,8(0) False negative errors (failure to recognize) – 35(33);27(20);5(16)—32(4);24(3);45(3)

74. Test Performance for 1018 subjects  82 (8%) had perfect scores,  230 (23%) made 1 error (98% correct),  700 (69%) made 5 or fewer errors (>90% correct),  132 (13%) made 6 – 10 errors (80 – 88% correct),  186 (18%) made > 10 errors ( 10 errors (<80% correct).--------------------------------------------------------------------  70 (7%) scored < 80% correct for True Negatives  19 (6%) males, 51 (8%) females (false positive responses = saying a picture is repeated when not), (false positive responses = saying a picture is repeated when not),  79 (8%) scored < 80% correct for True Positives  25 (7%) males, 54 (8%) females (false negative responses = failure to recognize/recall repeat picture). (false negative responses = failure to recognize/recall repeat picture).

77. Benefits of Early Alzheimer Diagnosis Social   Undiagnosed AD patients face avoidable problems social, financial   Early education of caregivers how to handle patient (choices, getting started)   Advance planning while patient is competent will, proxy, power of attorney, advance directives   Reduce family stress and misunderstanding caregiver burden, blame, denial   Promote safety driving, compliance, cooking, etc.   Patient’s and Family’s right to know especially about genetic risks   Promote advocacy for research and treatment development

78. Benefits of Early Alzheimer Diagnosis Medical   Early diagnosis and treatment and appropriate intervention may:   improve overall course substantially   lessen disease burden on caregivers / society   Specific treatments now available (anti-cholinesterases, memantine)   Improve cognition   Improve function (ADLs)   Delay conversion from Mild Cognitive Impairment to AD   Slow underlying disease process, the sooner the better   Decreased development of behavior problems   Delay nursing home placement, possibly over 20 months   Delay nursing home placement longer if started earlier

79. Issues for Memory Screening   Current testing for memory problems is based on having a tester sit in front of a subject for a prolonged period of time and administer unpleasant tests   Testing must be   Inexpensive (minimal need for administrator)   Fun (so people will return for frequent testing)   More precise, reliable, and valid To improve sensitivity To improve specificity

80. Tests Available On-Line   www.memtrax.com www.memtrax.com   www.memtrax.net www.memtrax.net   www.medafile.com www.medafile.com   www.cogolog.com www.cogolog.com   For further information, contact:   Wes Ashford: washford@medafile.com