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O  =<%H Screening for Alzheimer s disease 0%%!(x Herman Buschke, MD Einstein Aging Study (NIA AG-03949) Department of Neurology Albert Einstein College of Medicine Zy(b;Is screening needed to improve detection of Alzheimer s disease ?BB N  & 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) P P B "&;ZL,@DScreening is needed to improve detection of Alzheimer s disease AA 6 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 P7 Pq P P P J Screening Tests0 $ 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 Z Zb Z Z2 Z Z0 ZZZ !!vScreening for Alzheimer s disease by screening for memory impairment GG#h 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 f)  "VP Sensitivity and SpecificityQScreening 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 pPP/ P PC P Ps P P9 Pq " P P PP # 6d)qh6|!Memory Impairment Screen (MIS) * 8"$$$   #Controlled Learning#Controlled Learning# assures attention and equal processing of all items induces deep semantic processing shows that individuals can identify items by their cues induces all individuals to do the same processing shows that the required processing was done ensures that decreased recall is due to impaired memory induces  Encoding Specificity to maximize recall ZV fZ fZ8 Z` fZ fZ8 P fZ2 Z fZZ    ! 8 2 , 8 2! Free Recall *$#$Category Cued Recall *#m Encoding Specificity$ #  specific encoding operations performed on what is perceived determine what is stored and what is stored determines what retrieval cues are effective in providing access to what is stored Tulving & Thomson, Psych Review, 1973, page 369 Encoding and retrieval must be coordinated. Z.ZZ/ ZZ ,1+[BEncoding Specificity'   & . the probability of retrieval varies directly with the compatibility of the trace and the cue, or the stored information and the retrieval information. Tulving, Elements of Episodic Memory, page 249 (1985) Encoding and retrieval must be coordinated. :&+  _c Encoding Specificity& ##F retrieval depends on cues effectiveness of cues depends on what was stored what was stored depends on encoding operations performed on what was perceived to maximize retrieval, acquisition & retrieval must be coordinated by controlled learning & retrieval: retrieval cues must be present at encoding Z " Z!Z2 " Z" Z0 " Z"" Z!ZZZZZ  2 S m+ k3MIS screening for dementia$o5Alternate Forms Reliability &## Two forms administered to 429 individuals at beginning and end of neuropsychological evaluation Intra-class correlation = 0.69 Coefficient Alpha = 0.67 for each form+8 ' dFADementia ROC curve = .94 Alzheimer ROC curve = .97 Dementia Discrimination$;Alzheimer Discrimination$$MIS versus 3-Word Recall * 23-Word Free Recall CMIS Free Recall `0MIS Free and Cued Recall lMIS and 3-Word ROC curves # Barcelona MIS % QK )Screening Tests are Not Diagnostic Tests!4* $$ $ 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    <     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 PB PT P PT P7 PEPUPHPLPLPP" ;@6*8/P!{13EFG<TCVLWMXhbP  0` ̙33` ` ff3333f` 333MMM` f` f` 3>?" dd/(|? 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X=^(y___PPT10Y+D=' @ = @B +  0yL0   d ( w d d  <1?d  <1?:d  <1?d  <1?pPd  <1?d  <1?pP  C xm XaƳXaƳ1 ?5  m    0  `A ?1 ?"`Ke $ 0 0 m XB   01?xMxXB   01?MXB   01?MXB   01?MH d 0ne ? X=^(y___PPT10Y+D=' @ = @B +N   0yL0 ]U (   d  <1?d  <1?:d  <1?d  <1?pPd  <1?d  <1?<uT\  C xm XaƳXaƳ1 ?p  m     0  `A ?1 ?"``\p $ 0 0 m XB   01?RXB   01? _ XB   01?}XB   01?  C   `m ee1?g a 9* Kuslansky, Buschke, Katz, Sliwinski, Lipton, JAGS, 2002^:c.cccH  0ne ? X=^(y___PPT10Y+D=' @ = @B +g  0  (  x  c $Pm 0  m  f  0A1?"`|EH  0ne ? X=^(y___PPT10Y+D=' @ = @B +  0L0 0X( w x  c $|q 0s  q  f  0A1?"`WH  0ne ? X=^(y___PPT10Y+D=' @ = @B +Y  0 x@( t r X S d q W0G  q  ^ X 6A1?H  0ne ? X=^(y___PPT10Y+D=' @ = @B +ך  0 PT(  T~ T s *0q 0ps  q  L x T# `B T 3 xB T 3  T tB CDE Fg  @   T tB CDE Fg  @Y q  T tB CDE Fg  @ 2   T tB CDE Fg  @    T tB CDE Fg  @/ A   T tB CDE Fg  @[` mx   T tB CDE Fg  @" 9   T tB CDE Fg  @   T tB CDE Fg  @   T tB CDE Fg  @ g   T tB CDE Fg  @5) G@  T tB CDE Fg  @a s  T tB CDE Fg  @   T tB CDE Fg  @o   T tB CDE Fg  @0 H  T tB CDE Fg  @S"  !  T tB CDE Fg  @9 K  T tB CDE Fg  @e v w  T tB CDE Fg  @ 7 O  T tB CDE Fg  @    T tB CDE Fg  @   T tB CDE Fg  @ }%  T tB CDE Fg  @? >Q V T tB CDE Fg  @k }  T tB CDE Fg  @   T tBCDE Fg @    T tBCDE Fg @ u*  !T tBCDE Fg @P Sk ` "T tBCDE Fg @ 1 ? #T tBCDE Fg @   $T tBCDE Fg @ 5  %T tBCDE Fg @] y  &T tBC DE Fg  @   'T tBCDE Fg  @   (T tBCDE Fg @) D  )T tBCDE Fg @k   *T tBCDE Fg @   +T tBCDE Fg @ z ~ ,T tBCDE Fg @4rPu -T tBCDE Fg @xim .T tBCDE Fg @_c /T tBCDE Fg @WZ 0T tBCDE Fg @BM]P 1T tBCDE Fg @FG 2T tB CDE Fg  @FG 3T tBCDE Fg @FG 4T tBCDE Fg @ F'G 5T tBCDE Fg @OFkG 6T tBCDE Fg @FG 7T tBCDE Fg @FG 8T tBCDE Fg @F4G 9T tBCDE Fg @]FxG :T tBCDE Fg @FG ;T tBCDE Fg @FG T tBCDE Fg @FG ?T tBCDE Fg @F G @T tBCDE Fg @7FBG< AT # y  < BT # yR y < CT # y ; < DT # y  < ET # y  < FT # yY  < GT # y B < HT # y  < IT # y  < JT # ya  < KT # y" I < LT # y  < MT # y  < NT # ya  < OT # y" I < PT # y  < QT # y  < RT # yo  < ST # y0 W  TT BC'DEF&'''@`{  UT BC'DEF&'''@` VT BC'DEF&'''@`t WT B*C"DEF&""**"@`@b XT B+C"DEF&""++"@` $/< YT # - ZT B)CDEF&))@`E [T B)CDEF&))@`\ \T B*CDEF&**@` ]T B*CDEF&**@`  ^T B,CDEF&,,@`$uP _T B(CDEF&((@`ji} `T B*CDEF&**@`[p aT B*CDEF&**@`N b bT B*CDEF&**@`0 @Z U cT B*CDEF&**@`t 3 G dT B*CDEF&**@` $ 8 eT B*CDEF&**@` # ) fT B*CDEF&**@`= g  gT B*CDEF&**@`   hT B*CDEF&**@`   iT B*CDEF&**@` 1  jT B*CDEF&**@`K u  kT B*CDEF&**@`   lT B*CDEF&**@`   mT B2CDEF&!22@` F  nT B)CDEF&))@`]   oT B*CDEF&**@`   pT B*CDEF&**@`   qT B+CDEF&++@`! L  rT B*CDEF&**@`e   sT B*CDEF&**@`   tT B*CDEF&**@`  uT B*CDEF&**@`/Y vT B*CDEF&**@`s wT B+CDEF&++@`| xT B*CDEF&**@`w$ yT B*CDEF&**@`<sf zT B*CDEF&**@`p {T B*CDEF&**@`m~ |T B*CDEF&**@`i2z }T B*CDEF&**@`Jftw ~T B+CDEF&++@`cs T B*CDEF&**@`_p T B*CDEF&**@`Z?k T B*CDEF&**@`WWh T B*CDEF&**@`Sd T B*CDEF&**@`P a T B+CDEF&++@`"MM] T B+CDEF&++@`dIZ T B*CDEF&**@`FW T B*CDEF&**@`BS< T # 0?JN T tBCDE Fg @   T tBCDE Fg @4 5  T tBCDE Fg @   T tBCDE Fg @< =  T tBCDE Fg @ T tBCDE Fg @FG T tBCDE Fg @   T tBCDE Fg @w x  T tBCDE Fg @   T tBCDE Fg @ T tBCDE Fg @ T tBCDE Fg @   T tBCDE Fg @4 5  T tBCDE Fg @   T tBCDE Fg @< =  T tBCDE Fg @ T tBCDE Fg @FG T tBCDE Fg @   T tBCDE Fg @w x  T tBCDE Fg @   T tBCDE Fg @ T tBCDE Fg @ T tBCDE Fg @> T tBCDE Fg @  > T tBCDE Fg @  > T tBCDE Fg @&'> T tBCDE Fg @> T tBCDE Fg @@A> T tBCDE Fg  @& T tBCDE Fg  @$%& T tBCDE Fg  @& T tBCDE Fg  @jk& T tBCDE Fg  @  & T tBCDE Fg  @S T & T tBCDE Fg  @  & T tBCDE Fg  @< = & T tBCDE Fg  @  & T tBCDE Fg  @  & T tBCDE Fg  @& T tBCDE Fg  @no& T tBCDE Fg  @& T tBCDE Fg  @UV& T tBCDE Fg  @& T tBCDE Fg  @& T tBCDE Fg  @& T tBCDE Fg @ T tBCDE Fg @   T tBCDE Fg @   T tBCDE Fg @&' T tBCDE Fg @ T tBCDE Fg @@A T tBCDE Fg @ T tBCDE Fg @$% T tBCDE Fg @ T tBCDE Fg @jk T tBCDE Fg @   T tBCDE Fg @S T  T tBCDE Fg @   T tBCDE Fg @< =  T tBCDE Fg @   T tBCDE Fg @   T tBCDE Fg @ T tBCDE Fg @no T tBCDE Fg @ T tBCDE Fg @UV T tBCDE Fg @ T tBCDE Fg @ T zBCDE Fg @ T zBCDE Fg @  T zBCDE Fg @  T zBCDE Fg @   T zBCDE Fg @ T 6Lq  q  C0&  T 6PQq  :v  D20&  T 64Vq  :  D40&  T 6[q  :  D60&  T 6d_q : D80&  T 6]q  E100&  T 6iq  C0&  T 6mq `  D20&  T 6rq   D40&  T 6wq y D60&  T 6|q  D80&  T 6q  E100& : T 3  9  T zBCDE Fg @   T zBCDE Fg @   T zBCDE Fg @ 9  T zBCDE Fg @ `|  T zB CDE Fg  @   T 6q  A  L3-Word* : T 3 7  4 T # l { 4 T # l { 4 T # l @{ 4 T # l Z{ 4 T # l {  T 6`q B   IMIS*  T <8q   cTrue Positives (Sensitivity) (   T 6hq   BFalse Positives (1 " Specificity)H"  T zBCbDE Fg b@DW  T 6\q  rJ  K= .78*  T 6@q 9   K= .92*  T Hȩq 1?0 $ <  H T 0ne ? X=^(y___PPT10Y+D=' @ = @B +  0 `h<(  hr h S lq u1  q   h c $Dq A q   H h 0ne ? X=^(___PPT10i.6+D=' @ = @B +  0 ppM(  p p0 s 0e0e[ MA b? 8c ?#" `  b q # p Bq 1?' 0 wMadrid ROC curve Dementia vs No Dementia Spanish-MIS --------------------- Spanish-MMSE ---------------------x) f f  f   f             H p 0ne ? X=^(___PPT10i.6 +D=' @ = @B +  0 /' (    Nq eex8 1  x  <A ??    Nq eeG@}A  ?BRAAK   Hq ee  T MIS* 2   Nq eew &r =  .622 p = .003D #  Tq ee7de  o-Normal 6 Path Aging 3 AD 5 VaD 5 FTD 1 DLB 1 &. -4   f`q ee1?G "MIS correlates with Braak stage * ># ((( t   Zq XaƳXaƳ1 ?'` N* Verghese, Buschke, Dickson, Kuslansky, Katz, Weidenheim, Lipton, JAGS, 2003 :OPC>  H  0ne ? X=^y___PPT10Y+D=' m = @B +U X 0tL0 d\( (  ( d ( <1?d ( <1?:d ( <1?d ( <1?pP ( S ~q XaƳXaƳ1 ?t  q   ( S ~@ XaƳXaƳ1 ? q  XB ( 01?H ( 0ne ? X=^(y___PPT10Y+D=' m = @B +U 3 0tL0 d\h(  hd h <1?d h <1?:d h <1?d h <1?pP h S ~y XaƳXaƳ1 ?t  y   h S ~y XaƳXaƳ1 ? y  XB h 01?wwH h 0ne ? X=^(y___PPT10Y+D=' m = @B +m 0 nf0 p(  pd p <1?   p Z|j jJjJ1?{  S7 V%%KKppd p <1?{Pd p <1?P d p <1?  p Z j jJjJ1?z  S6 l**VVd p <1?zPd  p <1?P  p N1 ??   j   pC x<%j FzpFzp1 ? @  j   H p 0޽hdS ? a(\ 0 (   C x$j t<t<1 ? >  j     N1 ??   j H  0޽hdS ? a( 0 zr T (  Td T <1?   T Z| jJjJ1?{  S3 V%%KKppd T <1?{Pd T <1?P d T <1?  T Z jJjJ1?{  S3 l**VVd T <1?{Pd  T <1?P  T  T1 ??     T S ~ FzpFzp1 ? >    H T 0޽hdS ? a( 0 ph l(  ld l <1?   l Z)y jJjJ1?{  T29 V%%KKppd l <1?{Pd l <1?P d l <1?  l Z4y jJjJ1?{  T23 l**VVd l <1?{Pd  l <1?P  l N1 ??   y   lC x?y FzpFzp1 ? >  y   H l 0޽hdS ? a(  0 P(  PX P C ?   ;  P S p;  >  ;   H P 0޽hdS ? a(80___PPT10.ė 0 zr d (  dd d <1?   d Zx` jJjJ1?{  S3 V%%KKppd d <1?{Pd d <1?P d d <1?  d Z:^ jJjJ1?{  S3 l**VVd d <1?{Pd  d <1?P  d  T1 ??   `   d S ~_ FzpFzp1 ? >  `   H d 0޽hdS ? a( 0 zrP  (  d  <1?    Z#5 jJjJ1?{  S3 V%%KKppd  <1?{Pd  <1?P d  <1?   ZW5 jJjJ1?{  S3 l**VVd  <1?{Pd   <1?P    T1 ??   5    S ~\5 FzpFzp1 ? >  5   H  0޽hdS ? a( 0 zr0  (  d  <1?    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"2 1&Herman Buschke, MD.-@"Arial-. 12 @Einstein Aging Study (NIA AG.-@"Arial-.  2 @q-K.-@"Arial-. 2 @s03949).-@"Arial-. *2 H-Department of Neurology.-@"Arial-. <2 Q#Albert Einstein College of Medicine.-(--%--'՜.+,0$   Custom:"  *Times New RomanArial Helvetica Wingdings PowerpntMicrosoft Word DocumentPicture (Metafile)% Screening for Alzheimers disease BIs screening needed to improve detection of Alzheimers disease ?AScreening is needed to improve detection of Alzheimers disease Screening TestsGScreening for Alzheimers disease by screening for memory impairment Sensitivity and SpecificitySlide 7 Screening for memory impairment"Memory Impairment Screen (MIS) * Controlled LearningControlled Learning Free Recall *Category Cued Recall * Encoding SpecificityEncoding Specificity Encoding Specificity(Controlled Learning + Controlled Recall Slide 18MIS screening for dementiaAlternate Forms Reliability Dementia ROC curve = .94Alzheimer ROC curve = .97Dementia DiscriminationAlzheimer DiscriminationMIS versus 3-Word Recall * 3-Word Free RecallMIS Free RecallMIS Free and Cued RecallMIS and 3-Word ROC curvesBarcelona MIS Slide 31 Slide 32*Screening Tests are Not Diagnostic Tests! 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