1. Screening for Alzheimer’s disease Herman Buschke, MD Einstein Aging Study (NIA AG-03949) Department of Neurology Albert Einstein College of Medicine

2. Is screening needed to improve detection of Alzheimer’s disease ? “…nearly 75% of patients with moderate to severe dementia are unrecognized by primary care clinicians…” (Gifford & Cummings, Neurology,1999) “90% of generalists determine diagnosis of dementia by clinical impression, and 82% are confident about their recognition of mild dementia” (Swearer, Lester, Boudreau & Drachman, American Neurological Association, 2002)

3. Screening is needed to improve detection of Alzheimer’s disease we need a simple, rapid, accurate screening test with good sensitivity and good specificity that can be used by primary care clinicians to screen everyone at risk an efficient screen for AD must be easy to administer, interpret, and repeat, so that everyone at risk can be screened regularly

4. Screening Tests Screening tests are not diagnostic tests Screening tests select persons for diagnostic testing Screen everyone at risk, without “pre-screening” Repeat screening if risk persists or increases

5. Screening for Alzheimer’s disease by screening for memory impairment Memory impairment is required for diagnosis Memory impairment is usually the earliest sign Screening for memory impairment is necessary Effective screening for Alzheimer’s disease requires an efficient screening test for memory impairment with good specificity as well as good sensitivity

6. Sensitivity and Specificity DISEASE * NO DISEASE * 100 % 80 % 60 % 40 % 20 % SENSITIVITY SPECIFICITY * according to the “Gold Standard”

8. Screening for memory impairment Sensitivity is necessary to detect impairment Specificity is necessary for ethical, efficient (ppv) screening Maximum recall is needed to detect memory impairment because impairment means that maximum recall has decreased Controlled Learning and Controlled Recall are needed to elicit maximum recall by inducing encoding specificity, ensure that decreased recall is due to impaired memory

9. Memory Impairment Screen (MIS) *  Controlled Learning brief delay..  Free Recall  Cued Recall * Buschke, et al., Neurology,1999

10. Controlled Learning

11.  assures attention and equal processing of all items  induces deep semantic processing  shows that individuals can identify items by their cues  induces all individuals to do the same processing  shows that the required processing was done  ensures that decreased recall is due to impaired memory  induces “Encoding Specificity” to maximize recall

12. Free Recall *

13. Category Cued Recall * * only for items not retrieved by free recall

14. Encoding Specificity “specific encoding operations performed on what is perceived determine what is stored and what is stored determines what retrieval cues are effective in providing access to what is stored” Tulving & Thomson, Psych Review, 1973, page 369 Encoding and retrieval must be coordinated.

15. Encoding Specificity “…. the probability of retrieval varies directly with the compatibility of the trace and the cue, or the stored information and the retrieval information.” Tulving, Elements of Episodic Memory, page 249 (1985) Encoding and retrieval must be coordinated.

16. Encoding Specificity retrieval depends on cues effectiveness of cues depends on what was stored what was stored depends on encoding operations performed on what was perceived to maximize retrieval, acquisition & retrieval must be coordinated by controlled learning & retrieval: retrieval cues must be present at encoding

17. Controlled Learning + Controlled Recall coordinates encoding and retrieval by using the same cues for learning and retrieval induces encoding specificity which improves retrieval and discrimination of dementia because retrieval by aged without dementia is improved more than retrieval by aged with dementia

18. Recall with and without encoding specificity * * Buschke, Sliwinski, Kuslansky, Lipton, Neurology, 1997

19. MIS screening for dementia * Buschke, et al., Neurology, 1999

20. Alternate Forms Reliability Two forms administered to 429 individuals at beginning and end of neuropsychological evaluation Intra-class correlation = 0.69 Coefficient Alpha = 0.67 for each form

21. Dementia ROC curve =.94

22. Alzheimer ROC curve =.97

23. Dementia Discrimination

24. Alzheimer Discrimination

25. MIS versus 3-Word Recall * * Kuslansky, Buschke, Katz, Sliwinski, Lipton, JAGS, 2002

26. 3-Word Free Recall

27. MIS Free Recall

28. MIS Free and Cued Recall

29. MIS and 3-Word ROC curves 0 20 40 60 80 100 020406080100 3-Word MIS True Positives (Sensitivity) False Positives (1 − Specificity) =.78 =.92

30. Barcelona MIS

31. Madrid ROC curve Dementia vs No Dementia Spanish-MIS --------------------- Spanish-MMSE ---------------------

32. BRAAKBRAAK MIS r = –.622 p =.003 Normal 6 Path Aging 3 AD 5 VaD 5 FTD 1 DLB 1 MIS correlates with Braak stage * * Verghese, Buschke, Dickson, Kuslansky, Katz, Weidenheim, Lipton, JAGS, 2003

33. Screening Tests are Not Diagnostic Tests! Screening tests are not diagnostic tests Screening tests select persons for diagnostic testing Everyone at risk should be screened Diagnostic testing is required when screening is positive

34. MIS Summary  Screening for dementia depends on detection of memory impairment with good specificity and positive predictive value as well as good sensitivity  Screening requires controlled learning, controlled recall, and encoding specificity to elicit maximum retrieval by effective cued recall  MIS improves screening by controlled learning and controlled recall, to maximize recall and optimize sensitivity, specificity, positive predictive value  MIS is a simple, rapid, effective, easily administered screening test with good specificity as well as good sensitivity for Alzheimer’s disease  MIS is recommended by the American Academy of Neurology as a screen for AD