for hcp recos cccdtd4 en

8/17/2019 For Hcp Recos CCCDTD4 En

1/11

CANADIAN GERIATRICS JOURNAL, VOLUME 15, ISSUE 4, DECEMBER 2012 1

CLINICAL PRACTICE GUIDELINES/CONCENSUS

STATEMENTS

Recommendations of the 4th Canadian

Consensus Conference on the Diagnosis and

Treatment of Dementia (CCCDTD4)Serge Gauther , MD, Chr!t"#her $atter!"%, MD, &"'ar( Chert)"', MD, M*hae+ G"r("%, MD, Natha% &erra%%,

MD, -e%%eth R"*)'""(, MD, $e(r" R"!a.Net", ( , #h( , Jea%.$au+ S"u*/, MD "% eha+ " the CCCDTD4

#art*#a%t!

McGill Center for Studies in Aging, Montreal, QC

DOI:http://dx.doi.org/!."##!/cg$.".%&

ABSTRACT

The 4th CCCDTD *"%3e%e( % Ma/ 2012 % M"%trea+'th the #rar/ a " u#(at%g the #re3"u! (ag%"!t*

a#. #r"a*h t" AD, ta)%g %t" a**"u%t the re3!e(

(ag%"!t* *rtera #r"#"!e( / the I%ter%at"%a+ "r)%g

Gr"u# IG6 a%( the re*"e%(at"%! a(e / the

Nat"%a+ I%!ttute "% Ag%g7A+8heer A!!"*at"%

'"r)gr"u#!.

Key words: *"%!e%!u!, (ee%ta, A+8heer , (ag%"!!,

ag%g, !/#t"at* treate%t!

InTR oduCTIon

S%*e 19:9, three Ca%a(a% C"%!e%!u! C"%ere%*e! "% the

Dag%"!! a%( Treate%t " Dee%ta CCCDTD61,2,;6 ha3e

+e( t" e3(e%*e.a!e( re*"e%(at"%! "% the (ag%"!!

a%( treate%t " A+8heer

(ee%ta!= $re3"u! CCCCDTD! ha3e atte#te( t" a)e

re*"e%(a. t"%! re+e3a%t t" hea+th #r"e!!"%a+! " a++

(!*#+%e! treat%g (ee%ta e=g=, #rar/ *are

#ra*tt"%er!, a! 'e++ a! %eur"+". g!t!, geratr*a%!, a%(

#!/*hatr!t!6. Re*"e%(at"%! ha3e ee% #u+!he( %

e(*a+ >"ur%a+! rea*h%g "ut t" a '(e rea(er!h# !u*h a!

the Canadian Medical Association 'ournal CMAJ6, a! 'e++

a! "re !#e*a+8e( rea(er!h# !u*h a! the Canadian

'ournal of (eurological Sciences a%( Al)hei*er+s De*entia6. ?"++"'%g the +a!t CCCDTD % 200@, theCMAJ #u+!he( a !ere! " *a!e.a!e( art*+e! 'thre*"e%(a. t"%! "r ea*h !tage " AD a!/#t"at*

at r!) ,46 +( *"g%t3e #are%t,56 +( t" "(erate

(ee%ta,@,6 a%( !e3ere (ee%ta:66=

-A. Al ashed , . artha, 0 . erg*an, ' . ethell , S . lac1 , C .

octi, M. orrie, A. urha*, C . Coo1 , ' . Cro2son, M . Donnel3,

0 . 4eld*an, G. 0ec1*an, D. 0ogan, G.5.. 0siung , G. Inglis, C .

'aco6a, . 7aforce, 8 . 7anctot , 7. 7ee, 8 . 7eclair , M . Masselis,

4 . Massoud , A. Moore, S. 9rasad , 8 . aheru, D. Sado6nic1 , 7.

;rudeau, I .


2/11

CANADIAN GERIATRICS JOURNAL, VOLUME 15, ISSUE 4, DECEMBER 2012 2

The 4th CCCDTD *"%3e%e( % Ma/ 2012 %

M"%trea+ 'th the #rar/ a " u#(at%g the #re3"u!

(ag%"!t* a##r"a*h t" AD,96 ta)%g %t" a**"u%t the

re3!e( (ag%"!. t* *rtera #r"#"!e( / the I%ter%at"%a+

"r)%g Gr"u# IG610,116 a%( the re*"e%(at"%!

a(e / the Nat"%a+ I%!ttute "% Ag%g7A+8heer

A!!"*at"% '"r)gr"u#! NIAAA612,1;,146 t" 'h*h a

Ca%a(a% #er!#e*t3e ha! a+rea(/ ee% #u+!he(.156

eThodS

The eth"("+"g/ " the eet%g *a% e !uar8e( a! "+.

+"'! The #r"*e!! 'a! gu(e( / the te%et! " the AGREE

*"++a"rat"% t" 'h*h 20 " the 2; *rtera 'ere et.1@6

h+e #re3"u! CCCDTD! ha( u!e( the e3(e%*e gra(%g

!/!te (e3e+"#e( / the Ca%a(a% Ta!) ?"r*e "%

$re3e%t3e &ea+th Care, "r th! terat"% 'e atte#te( t"

"++"', 'here #"!!+e, the GRADE !/!te, % )ee#%g 'th

*urre%t re*"e%(at"%! "r the *"%(u*t " *"%!e%!u!

*"%ere%*e!=16

C"#+ete a*)gr"u%( art*+e! 'rtte% / '"r)gr"u#!

'ere #"!te( t" a #a!!'"r(.#r"te*te( 'e!te, a**e!!+e t"

a++ *"%ere%*e #art*#a%t!, 'h" 'ere e%*"urage( t" #"!t

*"e%t!. The re*"e%(at"%!, "( e( 'here

a#. #r"#rate a! a re!u+t " #art*#a%t!< *"e%t!, 'ere

the% #"!te( "r "%+%e 3"t%g. Orga%8at"%! re+e3a%t t"

the *are " #e"#+e 'th (ee%ta 'ere a##r"a*he( t"

a##"%t (e+. egate!= The!e (e+egate! ha( u++ a**e!! t" the

a*)gr"u%( art*+e!, 'ere e%*"urage( t" *"e%t, a%(

'ere a++"'e( t" 3"te "% re*"e%(at"%!= O%+%e 3"t%g'a! *+"!e( "%e (a/ e"re the *"%ere%*e a!!e+/, 'h*h

'a! he+( % M"%tra+ "% Ma/ 4th a%( 5th, 2012= At the

*"%ere%*e, ea*h t"#* 'a! re+/ re3e'e( e"re 3"t%g

'a! *arre( "ut "% ea*h re*"e%(at"%= A++ #art*#a%t!

e*e#t "r the "ur %(u!tr/ "!er3er!6 'ere #ertte( t"

3"te= I% the e3e%t " a+e( *"%!e%!u!, "%+%e 3"te! "

*"%ere%*e #art*#a%t! 'h" 'ere %"t a+e t" atte%( the

a!!e+/ 'ere ta)e% %t" a**"u%t= A! % ea*h #re3"u!

*"%!e%!u! *"%ere%*e, *"%!e%!u! 'a! (e%e( a! :0F "r

"re " *"%ere%*e #art*#a%t! 3"t%g

2012 Auth"r!6. $u+!he( / the Ca%a(a% Geratr*! S"*et/. Th! ! a% O#e% A**e!! art*+e (!trute( u%(er the ter! " the Creat3e C""%! Attrut"% N"%.C"er*a+

N".Der3at3e +*e%!e htt#*reat3e*""%!=" rg+*e%!e!/.%*.%(2=5*a6, 'h*h #ert! u%re!tr*te( %"%.*"er*a+ u!e a%( (!trut"%, #r"3(e( the "rg%a+ '"r) ! #r"#er+/ *te(.

http://creativecommons.org/licenses/by-nc-nd/2.5/cahttp://creativecommons.org/licenses/by-nc-nd/2.5/cahttp://creativecommons.org/licenses/by-nc-nd/2.5/cahttp://creativecommons.org/licenses/by-nc-nd/2.5/ca


3/11

GAUTHIER: RECOMMENDATIONS ON

"r the re*"e%(at"%. $arta+ *"%!e%!u! 'a! (e%e( a!

@0 H9F " 3"te!. Re*"e%(at"%! rea*h%g *"%!e%!u!

:0F6 are +!te( % the ta+e! " th! art*+e= Re*"e%(a.

t"%! rea*h%g "%+/ #arta+ "r %" *"%!e%!u! are *"e%te(

u#"% % the tet= Stre%gth " e3(e%*e ! +!te( % the ta+e!

'here #"!!+e= Re*"e%(at"%! *+ear+/ a##+*a+e "%+/

"r re!ear*h are +agge( 'th RK % the ta+e!.M"!t " the re*"e%(at"%! are #art*u+ar+/ re+e3a%t

t" !#e*a+!t! treat%g #ate%t! 'th (ee%ta e*au!e " the

%ature " the t"#*! (!*u!!e( (e%t"%!%e' (ag%"!t*

*rtera "r AD, u!e " %eur"ag%g a%( " +u(

"ar). er!, ear+/ "%!et (ee%ta, a%( ra#(+/

#r"gre!!3e (ee%ta= Re*"e%(at"%! "r the!e t"#*!

are there"re #re!e%te( % th! >"%t #u+*at"% % )e/

!#e*a+t/ >"ur%a+! % Ca%a(a the Canadian 'ournal of

(eurological Sciences a%( the Canadian 'ournal of

Geriatrics= S/#t"at* treate%t!, 'h*h are re+e3a%t t"

a++ treat%g #h/!*a%!, are a+!" re#"rte( % th! art*+e=

Definitions!"ew Diagnostic Criteria

The "t3at"% t" re3!e *rtera % Ca%a(a 'a! the e3"+u.

t"% " th%)%g a"ut h"' (ee%ta ght e a##r"a*he(

TABLE 1=

Re*"e%(at"%! regar(%g (e1%t"%! " (ee%ta, AD, a%( VCI

• e re*"e%( the a("#t"% " the *rtera "r (ee%ta #r".

#"!e( / the NIAAA '"r)%g gr"u# % 2011=

• e re*"e%( the a("#t"% " the *rtera *"%*er%%g #r".

a+e a%( #"!!+e A+8heer

the NIAAA '"r)%g gr"u# % 2011=• e re*"e%( the a("#t"% " the *rtera "r MCI (ue t"

AD

#r"#"!e( / the NIA.AA '"r)%g gr"u# % 2011=

• e re*"e%( rea!!e!!e%t " the ut+t/ " the *"%*e#t "

#r"(r"a+ AD % the uture 'he% "ar)er! are a3a+a+e,

3a+(ate(, a%( rea(/ "r u!e % Ca%a(a=

• e re*"e%( the IG (e1%t"% " a!/#t"at* at.r!)

"r

AD "%+/ "r re!ear*h #ur#"!e!=

• G3e% that the #re!e%*e " ra% a/+"( % %"ra+ #e"#+e !

" u%*erta% !g%*a%*e, 'e (!*"urage the u!e " a/+"(

ag%g % %(3(ua+! 'th"ut e"r/ +"!!, "ut!(e " the

re!ear*h !ett%g= The e(*a+ *"u%t/ !h"u+( e *+ear %t! (!*u!!"%! 'th #ate%t!, the e(a, a%( the ge%era+

#"#u+a. t"% that the #re!e%*e " ra% a/+"( % %"ra+

#e"#+e ! " u%*+ear !g%*a%*e at the #re!e%t te=

• e re*"e%( the 2011 ASAA&A re*"e%(at"%! "r

the (ag%"!! " VCI=% +ght " %e' *rtera % the U%te( State!= A #r"#"!a+ 'a!

a(e / the IG +e( / Bru%" Du"! a%( &"'ar( ?e+(a%

t" (ag%"!e AD e3e% e"re (ee%ta ha! e*"e a%e!t,

u!%g a !#e** *+%*a+ #he%"t/#e e"r/ #are%t "

the h##"*a#a+ t/#e6 a%( a "ar)er .106 I% 2011, three

'"r)gr"u#! " the NIAAA re*"e%(e( *rtera "r the

(ag%"!! " (ee%ta *au!e( / AD,126 MCI (ue t" AD,1;6

a%( a!/#t"at* AD=146

The!e '"r)gr"u#! ha3eera*e( the Du"!?e+(a% #r"#"!a+ % t! re+a%*e "%

"ar)er!= I% a((t"%a+, the !tatee%t a"ut 3a!*u+ar

*"%trut"%! t" *"g%t3e #are%t VCI6 a%( (ee%ta

a(e / the Aer. *a% &eart A!!"*at"%Aer*a%

A*a(e/ " Neur"+"g/1:6 'a! a+!" ea%e(= Aga%!t th!

a*)gr"u%(, the CCCDTD4 re*"e%(at"%! are +!te( %

Ta+e 1=

The #ra*t*a+ e!!age! are 16 a re*"e%(at"% %

a3"r " the *rtera "r MCI (ue t" AD, ut t" e u!e( *au.

t"u!+/ a%( "%+/ % !#e*a+8e( *+%*a+ #ra*t*e 26 a !tr"%g

re*"e%(at"% aga%!t the (ag%"!! " #r"(r"a+ ADK

"ut!(e a re!ear*h !ett%g ;6 the re*"g%t"% " the a*t that

a% at.r!) !tate "r AD % a!/#t"at* #er!"%! !h"u+( ea(e "%+/ % a re!ear*h !ett%g a%( 46 the ea!uree%t "

ra% a/+"( (e#"!t"% u!%g $ET ag%g %

a!/#t"at* #er!"%! !h"u+( e #er"re( "%+/ % a

re!ear*h !ett%g

#ar$y %nset Dementia

I% the *"%tet " a% %ter%at"%a+ e"rt t" treat #e"#+e 'h"

*arr/ utat"%! "r ge%e! *au!%g ear+/ "%!et a+a+ AD,196 a%( the reue!t! "r e"r/ *"%!u+tat"%! "r #e"#+e %

(. +e, the !!ue " ear+/ "%!et (ee%ta =e=, #r"r t" age

@56 'a! ea%e(. The re*"e%(at"%! "ut+%e( % Ta+e

2 'ere a##r"3e( / *"%!e%!u! " :0F=


4/11

GAUTHIER: RECOMMENDATIONS ON

TABLE 2=

Re*"e%(at"%! regar(%g ear+/ "%!et (ee%ta

• A++ #ate%t! 'th ear+/ "%!et (ee%ta !h"u+( e reerre( t" a

e"r/ *+%*, #reera+/ "%e 'th a**e!! t" ge%et* *"u%!e+.

+%g a%( te!t%g 'he% a##r"#rate=

• The *"!t " ge%et* *"u%!e++%g a%( te!t%g !h"u+( e *"3ere(

/ #u+* u%(%g=

• $h/!*a%! !h"u+( e !e%!t3e t" the !#e*a+ !!ue! a!!"*ate(

'th ear+/ "%!et (ee%ta, #art*u+ar+/ % regar( t" +"!! " e#+"/e%t a%( a**e!! t" !u##"rt !er3*e! a##r"#rate "r

that age gr"u#=

• C"%!(er%g the rart/ " ear+/ "%!et (ee%ta, a %at"%a+

reg!tr/ "r %tere!te( at.r!) %(3(ua+!, utat"% *arrer!

a%( !/#t"at* #ate%t! '++ a*+tate thera#eut* re!ear*h=

• Th! reg!tr/ !h"u+( e !u##"rte( / #u+* u%(%g=

The #ra*t*a+ e!!age ! that #ate%t! 'th (ee%ta

!tart. %g e"re age @5 !h"u+( e reerre( t" a !#e*a+!t,

#reera+/ % a *+%*a+ !ett%g 'here ge%et* *"u%!e++%g

a%( te!t%g ! a3a+a+e= The CCCDTD ha( re*"e%(e(

% 1999 that a++ !u*h #ate%t! e reerre( t" a !#e*a+!t. The

*urre%t CCCDTD re*"e%(! that e3e% a"%g !#e*a+!t!,

reerra+ !h"u+( e a(e t" *"++eague! 'th !#e*a+ e#ert!e

% th! area=

Ra&id$y 'rogressie Dementia

I% the *"%tet " %*rea!%g a'are%e!! " the a%/ *au!e!

" r a#( +/ #r"g re!!3e (ee %t a R $D6, #a r t *u

+a r+/


5/11

Creut8e+(t-Ja)" D!ea!e, a a%(at"r/ re#"rta+e *"%(.

t"% % Ca%a(a, the CCCDTD e+t the %ee( t" (e%e th!

*"%(t"% "#erat"%a++/ a%( !ugge!te( a##r"#rate reer.

ra+= ?urther"re the *""% "**urre%*e " ra#( *+%*a+

(e*+%e % +ater "%!et (ee%ta !u*h a! AD (e!er3e( a

re*"e%(at"%= The re*"e%(at"%! +!te( % Ta+e ;

'ere a##r"3e( u%a%"u!+/.

The #ra*t*a+ e!!age! are 16 #ate%t! 'th R$D'here the (ag%"!! rea%! u%*erta% !h"u+( e reerre(

ra#(+/ t" a##r"#rate !#e*a+t/ !et t%g! a%( 26 #ate%t!

'th )%"'% AD 'h" (e"%!trate a!ter -tha%-e#e*te(

*+%*a+ (e*+%e !h"u+( e rea!!e!!e( "r *"."r(

*"%(t"%!.

"euroimaging

Neur"ag%g 'a! the "!t *"#+e t"#* % th! r"u%( "

CCCDTD (!*u!!"%!. Re+e*t%g the a%/ te*h%*a+ a(.

3a%*e! % th! area, the t"#* 'a! "#erat"%a++/ (3(e(

%t" a% %tr"(u*t"% 'th ge%era+ re*"e%(at"%!,

!tru*tura+ %eur"ag%g CT a%( MRI6, u%*t"%a+ MRI,

$ET ag. %g (!*u!!%g "th 1:?DG a%( a/+"(.

%(%g +ga%(! ag%g6, S$ECT *erera+ +""( +"'

!tu(e! a%( MRI !#e*tr"!*"#/= Ma%/ " the

re*"e%(at"%! are re!ear*h re+ate(, !%*e e' " the!e

te!t! are u%3er!a++/ a3a+a+e "r *+%*a+ #+ee%tat"%

at th! te= The !!ue " 'hether a++ #ate%t! 'th

(ee%ta !h"u+( ha3e !tru*tura+ ag%g ! (eate( at

e3er/ CCCDTD *"%ere%*e, 'th the "#%"% that t ! %"t

reure( % a++ #ate%t!, ut rather "r th"!e 'h" ha3e

!#e*a+ *+%*a+ eature! Ta+e 4 r" $atter!"% et a+.266.

O%e #art*#a%t !ugge!te( that the age " @0 % that +!t 'a!

artrar/ a%( !h"u+( e (e+ete(= $art*#a%t! 3"te( aga%!t

the re*"e%(at"% that at +ea!t "%e !tru*tura+ . ag%g

#r"*e(ure !h"u+( e ("%e t" e!ta+!h the #re!e%*e "

TABLE ;=

Re*"e%(at"%! regar(%g ra#(+/ #r"gre!!3e (ee%ta

• It ! !ugge!te( that R$D e (e%e( a! a (ee%ta 'h*h (e.

3e+"#! 'th% 12 "%th! ater the a##eara%*e " 1r!t

*"g%t3e !/#t"! Gra(e 2C6=

• It ! !ugge!te( that %(3(ua+! !u!#e*te( " R$D e reerre(

t" #h/!*a%! 'h" are e#ere%*e( a%( ha3e a**e!! t" the

(ag. %"!t* a*+te! a+e t" "u%t a% "rga%8e( a%(*"#rehe%!3e (ag%"!t* #r"*e(ure Gra(e 2C6=

• Ater e*+u!"% " (e+ru a%( e3(e%t u%(er+/%g *au!e! "

R$D, t ! !ugge!te( that a (ag%"!t* !trateg/ "r R$D e

a!e( " the #re3a+e%*e " *au!e! " R$D % *a!e !ere!

Gra(e 2B6=

• The (ag%"!t* !trateg/ !h"u+( e#ha!8e the (ete*t"% "

#"te%ta++/ *ura+e *"%(t"%!, !u*h a! %e*t"%!, u%e

e(ate( a%( t"* eta"+* *au!e! Gra(e 2B6=

• ?"r %(3(ua+! 'th AD, t ! !ugge!te( that a (e*+%e " ; "r

"re #"%t! "% the MMSE % @ "%th!, 'h*h (e%t1e! a

gr"u# 'th a '"r!e #r"g%"!!, ! a !g%a+ t" e#+"re *".

"r( *"%(. t"%! a%( re3e' #hara*"+"g*a+ a%agee%t

Gra(e 2B6=

*+%*a++/ u%!u!#e*te( *erer"3a!*u+ar (!ea!e a%( t" ru+e

"ut #"te%ta++/ re3er!+e !tru*tura+ et"+"ge! % #er!"%!

'th *"g%t3e #are%t 2@F6. The re*"e%(at"%

that &ea+th Ca%a(a a##r"3e the u!e " $ET a/+"(

ag%g % tertar/ *are (ee%ta *+%*! (( %"t rea*h

*"%!e%!u! @;F6= There 'a! "%+/ #arta+ *"%!e%!u! "r the

#r"#"!t"% that "r a #ate%t 'th MCI e3a+uate( / a

(ee%ta !#e*a+!t a%( % 'h" *+%*a+ a%agee%t'"u+( e %1+ue%*e( / e3(e%*e " a% u%(er+/%g

%eur"(ege%erat3e #r"*e!!, a% 1:?-?DG $ET !*a% e

#er"re( "r, %"t a3a+a+e, the% a S$ECT rCB? !tu(/

e #er"re( 2F6 !ee Ta+e! 4 t" 106.

The #ra*t*a+ e!!age ! that !tru*tura+ ag%g ! %"t

reure( % a++ a+th"ugh '++ e %(*ate( % "!t6 #er!"%!

'th *"g%t3e #are%t= A+th"ugh "re *"!t+/ a%( +e!!

a3a+a+e, MRI ! #reera+e t" CT. here a3a+a+e,

$ET-1:?DG a%("r $ET a/+"( ag%g *a% e u!e( "r

*+%*a+

#ur#"!e % #ate%t! 'th at/#*a+ (ee%ta!=

TABLE 4=

Re*"e%(at"%! r" CCCDTD2 a"ut CT !*a% %ee(e(

• age +e!! tha% @0

/ear!

• ra#( e=g=, 1 "r 2 "%th!6 u%e#+a%e( (e*+%e % *"g%t"%

"r u%*t"%

• !h"rtK (urat"% " (ee%ta +e!! tha% 2

/ear!6

• re*e%t a%( !g%*a%t hea(

traua

• u%e#+a%e( %eur"+"g*a+ !/#t"! e=g= %e' "%!et " !e3ere

hea(a*he "r !e8ure!6

• h!t"r/ " *a%*er e!#e*a++/ % !te! a%( t/#e! that

eta!ta!8e t" the ra%6

• u!e " a%t*"agu+a%t! "r h!t"r/ " +ee(%g

(!"r(er

• h!t"r/ " ur%ar/ %*"%t%e%*e a%( gat (!"r(er ear+/ % the

*"ur!e " (ee%ta a! a/ e "u%( % %"ra+ #re!!ure h/.

(r"*e#ha+u!6

• a%/ %e' +"*a+8%g !g% e=g=, he#are!! "r a Ba%!)

re+e6

• u%u!ua+ "r at/#*a+ *"g%t3e !/#t"! "r #re!e%tat"% e=g= #r"gre!!3e a#ha!a6

• gat

(!tura%*e

TABLE 5=

Re*"e%(at"%! a"ut ?DG.$ET a%( S$ECT rCB? ag%g

• ?"r a #ate%t 'th a (ag%"!! " (ee%ta 'h" ha! u%(erg"%e

the re*"e%(e( a!e+%e *+%*a+ a%( !tru*tura+ ra%

ag%g e3a+uat"% a%( 'h" ha! ee% e3a+uate( / a

(ee%ta !#e*a+. !t ut 'h"!e u%(er+/%g #ath"+"g*a+

#r"*e!! ! !t++ u%*+ear, #re3e%t%g a(euate *+%*a+a%agee%t, 'e re*"e%( that the !#e*a+!t "ta% a


6/11

1:?.?DG $ET !*a% "r (ere%ta+ (ag%"!! #ur#"!e!

Gra(e 1B6=

• I !u*h a #ate%t *a%%"t e #ra*t*a++/ reerre( "r a H?DG.

$ET !*a%, 'e re*"e%( that a S$ECT rCB? !tu(/ e

#er"re( "r (ere%ta+ (ag%"!! #ur#"!e! Gra(e 2C6=


7/11

TABLE @=

Re*"e%(at"%! regar(%g !tru*tura+ ag%g, CT, a%( MRI

• e re*"e%( a hea( MRI 'he% a

ra("+"g!t%eur"ra("+". g!t a%("r a *"g%t3e !#e*a+!t

%eur"+"g!t, geratr*a%, "r geratr* #!/*hatr!t6 *a%

%ter#ret #atter%! " atr"#h/ a%( "ther eature! that a/

#r"3(e a((e( (ag%"!t* a%( #re(*t3e 3a+ue a! (eee(

a##r"#rate / the !#e*a+!t Gra(e 2B6=

• Sta%(ar(8at"% " *+%*a+ a*u!t"% " *"re MRI (ee%ta

!eue%*e! ! re*"e%(e( % Ca%a(a% Ce%ter! that ha3e ra.

("+"g!t! a%( *"g%t3e !#e*a+!t! 'th e#ert!e %

a!!e!!%g *"g%t3e (!"r(er!, #art*u+ar+/ 'he% re#eat MRI

age! *a% #r"3(e a((t"%a+ (ag%"!t*, #r"g%"!t* a%(

!aet/ %"ra. t"% Gra(e 2B6=

• I% a((t"% t" #re3"u!+/ +!te( %(*at"%! "r !tru*tura+ .

ag%g, a CT "r MRI !h"u+( e u%(erta)e% % the a!!e!!e%t

" a #er!"% 'th *"g%t3e #are%t the #re!e%*e " u%.

!u!#e*te( *erer"3a!*u+ar (!ea!e '"u+( *ha%ge the *+%*a+

a%agee%t=

• he% a3a+a+e % the *+%*, 'e re*"e%( that *"g%t"%

!#e*a+!t! u!e the *"#uter age! " the ra% t" e(u*ate

#er!"%! 'th *"g%t3e #are%t a"ut *ha%ge! % the

ra%= Th! )%"'+e(ge a/ re%"r*e a(here%*e t" 3a!*u+ar

r!) a*. t"r! a%agee%t a%( t" +e !t/+e "(*at"%! t"

#r"3e ra% hea+th Gra(e ;C6=

TABLE = Re*"e%(at"%! regar(%g

u%*t"%a+ MRI

• e re*"e%( aga%!t the u!e " MRI "r the *+%*a+ %.

3e!tgat"% " #ate%t! #re!e%t%g 'th *"g%t3e *"#+a%t

Gra(e 1B6=

• ?uture !tu(e! !h"u+( u!e !ta%(ar(8e( a*u!t"% " age! #r"t"*"+ a%( e#ere%ta+ #ara(g t" a++"' #""+%g " (ata

Gra(e 1CR6=

• ?uture !tu(e! 'th +arge %uer " #art*#a%t! a%( +"%ger

#er"( " "++"'.u# are %ee(e( t" a++"' r *"%*+u!"%! "%

the 3a+ue " MRI % ear+/ (ete*t"% " (ee%ta a%( "% #re.

(*t%g *"%3er!"% " MCI t" AD Gra(e 1B R6=


#er"( " "++"'.u# are %ee(e( t" a++"' r *"%*+u!"%! re.

gar(%g the 3a+ue " MRI % (!t%gu!h%g et'ee% AD a%(

%"%.AD (ee%ta !u*h a! ?TD a%( LBD Gra(e 1B R6=


#er"( " "++"'.u# are %ee(e( t" a++"' r *"%*+u!"%! "%

the 3a+ue " MRI % a!!e!!%g *ha%ge! % ra% a*t3at"% %re!#"%!e t" %ter3e%t"% !u*h a! *"g%t3e tra%%g a%( #har.

a*"thera#/ Gra(e 1C R6=


#er"( " "++"'.u# are %ee(e( t" a++"' r *"%*+u!"%! "%

the 3a+ue " MRI a##%g ra% a*t3at"% % 3ar"u! %eu.

r"#!/*hatr* a%( eha3"ra+ !/#t"! % the *"%tet " #re.

*+%*a+ a%( *+%*a+ (ee%ta !u*h a! (e#re!!"%, a#ath/ a%(

TABLE :=

Re*"e%(at"%! regar(%g $ET a/+"( ag%g

• A+th"ugh a/+"( ag%g re#re!e%t! a #r"!%g

te*h%ue % the e3a+uat"% " (ee%ta, there are a%/

u%)%"'%! that *"u+( #a*t "% t! (ag%"!t* ut+t/ a%(

there"re 'e re*"e%( that t! u!e e re!tr*te( t"

re!ear*h at #re!e%t Le3e+ 1C R6.

• A/+"( ag%g ! %"t *urre%t+/ a##r"3e( % Ca%a(a.Sh"u+( a/+"( ag%g e*"e a3a+a+e t" Ca%a(a% *+.

%*a%! % the uture, t u!t %"t e *"%!(ere( a r"ut%e

te!t a%( 'e re*"e%( t ! regar(e( a! a% a(>u%*t t" a

*". #rehe%!3e e3a+uat"% "r *"#+e at/#*a+

#re!e%tat "%! % reerra+ t" tert ar/ *are Me"r/ C+%*!

'he% a "re a*. *urate *+%*a+ (ag%"!! ! %ee(e( Gra(e

1B6.

• Sh"u+( th! te*h%ue e*"e a3a+a+e t" Ca%a(a% *+%.

*a%! % the uture, 'e re*"e%( aga%!t t! u!e % *"g%.

t3e+/ %"ra+ %(3(ua+! "r "r the %ta+ %3e!tgat"% "

*"g%t3e *"#+a%t! Gra(e 1B6.

• he% a*e( 'th a/+"( te!t re!u+t! "ta%e( "ut!(e

Ca%. a(a, #h/!*a%! !h"u+( e 3er/ *aut"u! % ther %ter#re. tat"%, .e= u!e( % !"+at"% th! te!t *a%%"t

(ag%"!e AD, MCI, "r (ere%tate %"ra+ r" a%"ra+

ag%g, a%( 'e re*"e%( the/ *"%!u+t 'th a (ee%ta

!#e*a+!t a+. ar 'th th! te*h%ue.

• At #re!e%t, there ! %" *+%*a+ %(*at"% "r a/+"( .

ag%g % *"g%t3e+/ %"ra+ %(3(ua+!, %ta+ %3e!tga.

t"% " *"g%t3e *"#+a%t!, (ere%tat%g AD r" "ther

A -a!!"*ate( (ee%ta e.g= DLB, CAA6, (ere%tat%g

et'ee% AD *+%*a+ 3ara%t! e.g., *+a!!* a%e!t*

AD 3!= $CA "r +3$$A6, a%( (ere%tat%g et'ee% %"%-

AD *au!e! " (ee%ta e.g., "+e*u+ar !ut/#e! "

?TLD6.

• I% re!ear*h !ett%g! 'th a/+"( ag%g *a#a+te!, %.

3e!tgat"r! !h"u+( e e%*"urage( t" (e3e+"# #r">e*t! that

urther 3a+(ate the *+%*a+ a%( re!ear*h u!e! " th! te*h.

%ue a%( e3a+uate t rea(%e!! "r tra%!+at"% t" *+%*a+

*are R6.

• Tra+ (e!g%er! are !tr"%g+/ e%*"urage( t" u!e th! te*h.

%ue t" 16 (e*rea!e the heter"ge%et/ " ther MCI #"#u.

+at"% 26 (e%t/ a *"h"rt that ! +)e+/ t" re!#"%( t" a

(rug 'th a%t-a/+"( #r"#erte! a%( ;6 !tu(/ #ate%t!

that are +)e+/ t" *"%3ert t" AD % a re+at3e+/ !h"rt te

rae R6.

• Te!t%g a%( +"%gtu(%a+ "++"'.u# " a!/#t"at* %(.

3(ua+! "r #ate%t! 'th !u>e*t3e *"g%t3e #are%t!

%"t eet%g MCI *rtera, "r at-r!) %(3(ua+! e.g=, ge%e

utat"% *arrer!, a+/ h!t"r/ " AD, A#"E 46 !h"u+(

e re! tr*te( t" re!ear*h R6.

• ?uture re!ear*h !h"u+( e#+"re 16 the %atura+ e3"+ut"% "

a/+"( ur(e% a%( t! r"+e % the #ath"#h/!"+"g/ " AD

a%( "ther (ee%ta!, 26 t! u!e a! a #"te%ta+ !urr"gate

ar)er "r a%t-a/+"( thera#e!, ;6 the 3a+ue " %e' 1:?

a/+"( tra*er!, a%( !h"u+( 46 #er"r $ET #ath"+"g/

*"rre+at"%!, a%( 56 *"#are a/+"( ag%g 'th CS?

AD "ar)er! a! 'e++ a! ("'%!trea ar)er! "

(ege%erat"% R6. #!/*h"!!, 'h*h '++ he+# % (e3e+"#%g !#e*1* treate%t!

"r the!e !/#t"! Gra(e 2C6=


8/11

i*uid Biomar+ers (see Ta,$e

--)

I% the *"%tet that *erer"!#%a+ 1+u( CS?6 ea%at"%

"r A42 a%( tau +e3e+! ! a *"#"%e%t " the "ar)er!

"r AD % the IG a%( the NIAAA *rtera, t 'a!

#"rta%t t" e3a+uate the ea!+t/ a%( 3a+(t/ " CS?

ea%at"% "r r"ut%e (ag%"!t* #ur#"!e "r % at/#*a+*a!e!= A+th"ugh e3er/"%e agree( that #+a!a A42 are %"t

re+a+e a%( are %"t re*"e%(e( "r *+%*a+ #ra*t*e, the

#r"#"!a+ that CS? A42 a%( tau +e3e+! e ea!ure( (( %"t

rea*h *"%!e%!u! @4F6, %"r (( the #r"#"!a+ that ea!ure!

" CS? A1-42, t"ta+ tau a%( #h"!#h"r/+ate( tau at !er 1:1

!h"u+( e *"+. +e*te( "++"'%g a !#e** #r"t"*"+ a%( the

ua%t*at"% u!t e *arre( "ut / a% e#ere%*e( +a

'th a 3a+(ate( te*h%"+"g/ a%( *"%t%u"u! #art*#at"% %

ua+t/ *"%tr"+ #r"gra! 1F6.

The #ra*t*a+ e!!age ! that, "r %"',

ea!uree%t " CS? A1-42 a%( tau ha3e %" *+%*a+

ut+t/ % Ca%a(a, a+th"ugh the/ are #art " re!ear*h

#r"t"*"+! % "!er3at"%a+ a%( thera#eut* !tu(e!=

.&date on Sym&tomatic

Treatments

A+th"ugh there ha3e ee% %" %e' (rug! a##r"3e( %

Ca%a(a "r e+!e'here !%*e the CCCDTD; eet%g %

200@, t 'a! *"%!(ere( #"rta%t t" re3e' %e' e3(e%*e

"% the %(*a. t"%! a%( e!t u!e " the!e (rug! Ta+e! 12

a%( 1;6. S#e*a+ e#ha!! 'a! #+a*e( "% (!*"%t%uat"%

ru+e! "r *h"+%e!. tera!e %ht"r! CI!6 'h*h ha3e %"t

#re3"u!+/ ee% *+ear+/ (e%e( % the +terature.

The #ra*t*a+ e!!age! are that 16 *"%*urre%t *au!e!" (ee%ta ha3e t" e a%age( 26 CI! are re*"e%(e(

"r AD % +( t" !e3ere !tage! " (ee%ta, AD 'th a

*ere-

TABLE 9

Re*"e%(at"%! regar(%g MR !#e*tr"!*"#/

• Mag%et* re!"%a%*e !#e*tr"!*"#/ !h"'! #r"!e "r #re.

(*t%g 'h*h #e"#+e 'th +( *"g%t3e #are%t are

+)e+/ t" #r"gre!! t" (ee%ta= &"'e3er, t ! %"t *urre%t+/

re*"e%(e( "r *+%*a+ u!e t" a)e "r (ere%tate a (.

ag%"!! " (ee%ta % #e"#+e #re!e%t%g 'th +(

*"g%t3e #are%t Gra(e 2C R6.

• 1& MRS rea%! a #r"!%g te*h%ue "r the

(e%t*at"% " !u>e*t! 'th +( *"g%t3e #are%t

'h" '++ *"%3ert t" (ee%ta= ?urther u+t-!te

+"%gtu(%a+ !tu(e! !h"u+( e *"%(u*te( t" e!ta+!h

%"rat3e 3a+ue!= Su*h !tu(e! !h"u+( ut+8e !ta%(ar(8e(

e%r"++e%t *rtera, (ag%"!! *rtera, (ata a*u!t"%

eth"(!, a%( %*+u(e aut"ate( a%a+/!! " !#e*tra that

%*"r#"rate! #r"#er #r"r )%"'+e(ge " eta"+te

+%e!ha#e! R6.

• Sta%(ar(8e( 1& MRS (ata a*u!t"% a%( a%a+/!!

eth"(! !h"u+( e (e3e+"#e( % *"."r(%at"% 'th

re*"e%(at"%! r" the I%ter%at"%a+ S"*et/ "

Mag%et* Re!"%a%*e % Me(*%e R6.

• ?uture 1& MRS !tu(e! t" (e"%!trate *+%*a+

ee*t3e%e!! !h"u+( ut+8e ; Te!+a MRI 'here a3a+a+e t"

%*rea!e (ata ua+t/ R6.

TABLE 10.

Re*"e%(at"%! regar(%g "ther %eur"ag%g "(a+te!

• Iag%g "ar)er! " %eur"-%+aat"% "r tau #ath"+.

"g/ % (ee%ta #ate%t! are %"t re*"e%(e( % *+%*a+

#ra*t *e=

• A+th"ugh there ! a gr"'%g "(/ " +terature !u##"rt%g

the u!e " ("#a%e #re!/%a#t* ag%g age%t! "r

(ere%tat%g Le'/ B"(/ r" AD (!ea!e, the!e ag%gage%t! are %"t /et re*"e%(a+e "r *+%*a+ #ra*t*e.

r"3a!*u+ar *"#"%e%t, $ar)%!"% D!ea!e (ee%ta, ut %"t

"r #r"a+e 3a!*u+ar (ee%ta ;6 the *"%at"% " CI!

a%( ea%t%e ! +"g*a+, ut a% a((t3e 0e%e1t ha! %"t

ee% *"%*+u!3e+/ (e"%!trate( 46 "r !e3ere agtat"%

the at/#. *a+ a%t#!/*h"t*! r!#er("%e, "+a%8a#%e a%(

ar##ra8"+e are re*"e%(e(, ut r!)! " thera#/ u!t

e *areu++/ 'eghe( aga%!t #"te%ta+ e%et! 56 there !

%!u*e%t e3(e%*e "r "r aga%!t CI!, ea%t%e,

SSRI!, "r tra8"("%e a! r!t-+%e thera#/ "r

%eur"#!/*hatr* !/#t"! a%( @6 3a+#r"ate !h"u+( %"t e u!e( "r agtat"% a%( aggre!!"%.

ConCuSIon

De!#te a +arge %uer " #"rta%t a(3a%*e!, the

CCCDTD4 *"%*+u(e( that u%(ae%ta+ *ha%ge! %

(ee%ta (ag%"!! a%( a%agee%t ha3e %"t /et arr3e(=

The IG a%( NIA AA AD *rtera *he+/ !er3e t" *"(/

!ta%(ar( #ra*t*e % !#e*a+t/ !ett%g! "r (ee%ta a%(

MCI (ue t" AD, a%( "r re!ear*h at a++ !tage! " AD . A!

re!u+t, Ca%a(a% #h/!*a%! 'h" are %"t (ee%ta e#ert!

'++ e +tt+e ae*te( / the CCCDTD4 re*"e%(at"%!=

The 1999 *"%!e%!u! re*". e%(e( that /"u%ger #ate%t!

th"!e P @5 /ear!6 a%( #ate%t!


9/11

TABLE 11= Re*"e%(at"%! regar(%g

+u( "ar)er!

• $+a!a A1H 42 +e3e+! are %"t re*"e%(e( "r

*+%*a+

# ra * t * e=

'th ra#(+/ #r"gre!!3e (ee%ta e reerre( t" (ee%ta

!#e*a+!t! a%( th! ha! %"t *ha%ge(, e*e#t that e3e%a"%g !#e*a+!t! % the (!*#+%e! t" 'h*h !u*h #ate%t!

ght e reerre(, tertar/ reerra+ " !u*h #ate%t! !h"u+(

e a(e t" *"++eague! 'th !#e*a+ e#ert!e "r that age

gr"u#.

I the u!e " "ar)er! e*"e! >u!te( / urther

e3(e%*e, th! '++ ha3e #+*at"%! "r h"' *"g%t3e

(e*+%e ! e3a+uate(, a%( +)e+/ '++ ha3e 3er/ !u!ta%ta+

e*"%"* #+*at"%!. E3e% %"', Ca%a(a% #h/!*a%!

e%gage( % (ee%ta re!ear*h '++ %ee( t" *"%!(er h"'

the %e' re!ear*h *rtera '++ #a*t ther a**e!! t"

ag%g "(a+te! a%( +a"rat"r/ te!t! that are %"t /et

!ta%(ar( "r (ee%ta *are % Ca%a(a.


10/11

TABLE 12=

Re*"e%(at"%! regar(%g !/#t"at* treate%t!

• Ma%/ *a!e! " (ee%ta ha3e "re tha% "%e *"%(t"% *"%.

trut%g t" *au!at"%. M"!t *""%+/ th! '++ e a

*". %at"% " A+8heer

"#t"% "r (ee%ta a!!"*ate( 'th $ar)%!"%

Gra(e 1A6.

• There ! %!u*e%t a%( %*"%!!te%t e3(e%*e "% 'h*h t"

a)e a re*"e%(at"% ether "r "r aga%!t the u!e " the

*urre%t+/ a3a+a+e *h"+%e!tera!e %ht"r! "r the

treate%t " 3a!*u+ar (ee%ta Gra(e 2B6.

• A++ three *h"+%e!tera!e %ht"r! ha3e (e"%!trate(

e*a*/ "r +( t" !e3ere AD. e re*"e%( a tra+ " a*h"+%e!ter. a!e %ht"r "r "!t #ate%t! 'th AD Gra(e

1A6.

• Dre*t *"#ar!"%! (" %"t !ugge!t (ere%*e! et'ee%

*h". +%e!tera!e %ht"r! Gra(e 2B6= Se+e*t"% " 'h*h

age%t t" e u!e( '++ e a!e( "% a(3er!e ee*t #r"+e,

ea!e " u!e, a+ar t/, a%( (ere%*e! et'ee% the age%t!

% ther #hara*")%et*! a%( "ther e*ha%!! " a*t"%.

• C" %at"% thera#/ " a *h"+ %e!tera!e % ht"r

a%( ea%t %e ! rat "%a+ a! the e(*at "%! ha3e

(ere%t e*ha%!! " a*t"%6 a%( a##ear! t" e !ae, ut

there ! %!u*e%t e3(e%*e t" re*"e%( "r "r aga%!t

th! *". %at"% Gra(e 2B6.

• I t he #at e%t ha( a % %a(eu ate re!#"%!e t" t he%"%. #hara*"+"g*a+ %te r3e%t "%! "r ha! a Ma>"r

De#re!!3e D!"r(er, !e3ere (/!th/a, "r !e3ere

e"t"%a+ + a +t/, 'e re*"e%( that a t ra+ " a%

a%t(e#re!!a%t *"u+( e *"%!(ere( Gra(e 2A6.

• Ba!e( "% g""( e3(e%*e 'e re*"e%( that 3a+#r"ate

!h"u+( %"t e u!e( "r agtat"% a%( aggre!!"% % AD

Gra(e 1A6.

• There ! %" g""( e3(e%*e t" re*"e%( "r "r aga%!t

the u!e " *h"+%e!tera!e %ht"r! a%("r ea%t%e "r

the treate%t " %eur"#!/*hatr* !/#t"! a! a #rar/

%(*at"% Gra(e 2B6.

• e re*"e%( that r!#er("%e, "+a%8a#%e a%(

ar##ra8"+e e u!e( "r !e3ere agtat"%, aggre!!"% a%(

#!/*h"!! a!!"*. ate( 'th (ee%t a 'here there ! r !) "

har t" the #ate%t a%("r "ther!. The #"te%ta+ 0e%e1t "

a++ a%t#!/*h"t*! u!t e 'eghe( aga%!t the !g%*a%t

r!)! !u*h a! *erer"3a!. *u+ar a(3er!e e3e%t! a%(

"rta+t/ Gra(e 2A6.

• There ! %!u11*e%t e3(e%*e t" re*"e%( "r "r aga%!t

the u!e " ueta#%e % the a%agee%t " !e3ere

agtat"%, ag. gre!!"% a%( #!/*h"!! a!!"*ate( 'th

(ee%ta Gra(e 2B6.

• There ! %!u*e%t e3(e%*e t" re*"e%( "r "r aga%!t

the u!e " SSRI! "r tra8"("%e % the a%agee%t "

agtate( #ate%t! Gra(e 2B6.

TABLE 1;= Re*"e%(at"%! regar(%g

(!*"%t%uat"% " *h"+%e!tera!e %ht"r!

• D!*"%t%u%g *h"+%e!tera!e %ht"r! % #ate%t! 'th

"(erate t" !e3ere A+8heer

%g " *"g%t3e u%*t"% a%( greater u%*t"%a+ #are%t

a! *"#are( t" *"%t%ue( thera#/ Gra(e 2B6= Th! u!t e

a+a%*e( 'th the r!) "r )%"'% !(e.ee*t! a%( (rug *"!t!

thera#/ *"%t%ue!. It ! !ugge!te( that *h"+%e!tera!e%ht"r! e (!*"%t%ue( 'he%

a6 The #ate%t a%("r ther #r"/ (e*!"%-a)er (e*(e

t" !t"# ater e%g a##ra!e( " the r!)! a%( e%et! "

*"%t%uat"% a%( (!*"%t%uat"%

6 The #ate%t ! !u11*e%t+/ %"%.a(here%t 'th the

e(*a. t"% that *"%t%ue( #re!*r#t"% " t '"u+( e

u!e+e!!, a%( t ! %"t #"!!+e t" e!ta+!h a !/!te "r

the a(%!tra. t"% " the e(*at"% t" re*t/ the

#r"+e

*6 The #ate%t

eha3- "ura+ (e*+%e ! greater "% treate%t *"#are(

t" that #r"r t" e%g treate(

(6 The #ate%t e#ere%*e! %t"+era+e !(e ee*t! that

are (e%te+/ "r #r"a+/ re+ate( t" the *h"+%e!tera!e

%ht"r

e6 The *""r(te! " the #ate%t a)e *"%t%ue( u!e

" the age%t ether u%a**e#ta+/ r!)/ "r ut+e e.g=,

ter%a++/ ++6

6 The #ate%tQ! (ee%ta #r"gre!!e! t" a !tage e.g.,

G+"a+ Deter"rat"% S*a+e !tage 6 'here there '"u+(

e %" *+%*a++/ ea%%gu+ e%et r" *"%t%ue(

thera#/.

• he% a (e*!"% ha! ee% a(e t" (!*"%t%ue thera#/

e*au!e " a #er*e3e( +a*) " ee*t3e%e!!, t ! !ugge!te(

that the ("!e e ta#ere( e"re !t"##%g the age%t a%( that

the #ate%t e "%t"re( "3er the %et 1-; "%th! "r

e3(e%*e " a% "!er3. a+e (e*+%e= I th! "**ur!, t !

!ugge!te( that *"%!(erat"% e g3e% t" re%!tat%g thera#/

Gra(e 2C6.

ACK nowedgeenTS

S%*ere tha%)! t" the !ta " Me(#+a% 'h" he+#e( #re#are

the %uer"u! te+e*"%ere%*e! #r"r t"7a%( the +"g!t*! "

7the CCDTD4 eet%g, a! 'e++ a! the !ta " the M*G++Ce%ter "r Stu(e! % Ag%g 'h" he+#e( (ur%g the eet%g

% M"%trea+=

Conf)ICTof InTeR eST

dISCoSuR eS The auth"r! (e*+are that %" *"%+*t!

" %tere!t e!t=RefeR enCeS

1= Orga%8%g C"ttee Ca%a(a% C"%!e%!u! C"%ere%*e "%

the A!!e!!e%t " Dee%ta= A!!e!!%g (ee%ta H the

Ca%a(a% *"%!e%!u!= CMA' = 1991144:51H5;=


11/11

2= $atter!"% C, Gauther S, Berga% &, et al = The re*"g%t"%,

a!!e!!e%t a%( a%agee%t " (ee%t%g (!"r(er! *"%*+u.

!"%! r" the Ca%a(a% C"%!e%!u! C"%ere%*e "% Dee%ta=

CMA' = 19991@012 !u##+6S1HS15=

;= Chert)"' &. Dag%"!! a%( treate%t " (ee%ta

I%tr"(u*t"%=

CMA' = 200:1:;1@H21=

4= $atter!"% C, ?eght%er J, Gar*a A, et al . Dag%"!! a%(treat. e%t " (ee%ta 1= R!) a!!e!!e%t a%( #rar/

#re3e%t"% " A+8heer (!ea!e= CMA' = 200:1:54:H5@=

5= Chert)"' &, Ma!!"u( ?, Na!re((%e , et al = Dag%"!! a%(

treate%t " (ee%ta ;. M+( *"g%t3e #are%t a%(

*"g%. t3e #are%t 'th"ut (ee%ta= CMA' .

200:1:12;H:5=

@= &"ga% DB Ba+e/ $, B+a*) S, et al. Dag%"!! a%(

treate%t " (ee%ta 4= A##r"a*h t" a%agee%t " +( t"

"(erate (ee%ta= CMA' = 200:19:H9;=

= &"ga% DB, Ba+e/ $, B+a*) S, et al = Dag%"!! a%( treate%t

" (ee%ta 5= N"%#hara*"+"g* a%( #hara*"+"g*

thera#/ "r +( t" "(erate (ee%ta= CMA' =

200:191019H2@=:= &erra%% N, Gauther S. Dag%"!! a%( treate%t " (e.

e%ta @= Ma%agee%t " !e3ere A+8heer (!ea!e= CMA' .

200:19129H:=

9= ?e+(a% &&, Ja*"3a C, R"++ar( A, et al . Dag%"!! a%(

treat. e%t " (ee%ta 2= Dag%"!!= CMA' = 200:1::25H

;@=

10= Du"! B, ?e+(a% &&, Ja*"3a C, et al = Re!ear*h *rtera "r

the (ag%"!! " A+8heer

ADRDA *rtera= 7ancet (eurol = 200@;4H4@=

11= Du"! B, ?e+(a% &&, Ja*"3a C, et al = Re3!%g the (e%.

t"% " A+8heer

(ag%". !! " (ee%ta (ue t" A+8heer

re*"e%(at"%! r" the Nat"%a+ I%!ttute "% Ag%gH

A+8heer

gu(e+%e! "r A+8heer

201120H9=

14= S#er+%g RA, A!e% $, Be*)ett L, et al . T"'ar( (e%%g the

#re*+%*a+ !tage! " A+8hheer

Al)hei*ers De*ent = 20112:0H92=

15= Gauther S, $atter!"% C, G"r("% M, et al . C"e%tar/

"%

KRe*"e%(at"%! r" the Nat"%a+ I%!ttute "% Ag%gHA+.

8heer

1:= G"re+*) $B, S*uter A, B+a*) SE, et al . Va!*u+ar

*"%trut"%! t" *"g%t3e #are%t a%( (ee%ta a

!tatee%t "r hea+th *are #r"e!!"%a+! r" the Aer*a%

&eart A!!"*at"%Aer. *a% Str")e A!!"*at"%= Stro1e=

2011422@2H1;=

19= u L, R"!a- Net" $, &!u %g G, et al . Ear+/- "%!et

a. +a+ A+8heer

for hcp recos cccdtd4 en

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