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DEMENTIA: Alzheimer’sDisease and Vascular
DementiaChristian Kamallan
Neurologist
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“I am living ith
dementia! not d"ingith dementia#$
ALZHEIMER'S DISEASE
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• Hippocampus: where short-term memories are converted to long-termmemories
• Thalamus: receives sensory and limbic information and sends tocerebral cortex
• Hypothalamus: monitors certain activities and controls body’s internalclock
• Limbic system: controls emotions and instinctive behavior (includes thehippocampus and parts of the cortex)
Inside the Human
Brain
Other rucial !arts
Slide 12
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The Brain in Action
Hearing Words Speaking Words Seeing Words Thinking about Words
"ifferent mental activities take place in different parts of the
brain# !ositron emission tomography (!$%) scans canmeasure this activity# hemicals tagged with a tracer &light
up' activated regions shown in red and yellow#
Inside the Human Brain
Slide 13
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Neurons
• %he brain has billions of
neurons each with an
axon and many
dendrites#
• %o stay healthy neurons
must communicate with
each other carry out
metabolism and repairthemselves#
• " disrupts all three of
these essential *obs#
Inside the
Human Brain
Slide 14
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Plaques and Tangles The Hall!arks o" A#
%he brains of people with " have an abundance of twoabnormal structures:
An actual A# plaque An actual A# tangle
• beta-amyloid pla+ues which are dense deposits of
protein and cellular material that accumulate outside
and around nerve cells
• neurofibrillary tangles which are twisted fibers that build
up inside the nerve cell
AD and the Brain
Slide 1$
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Cognitive ContinuumCognitive Continuum
NormalNormal
Mild CognitiveMild CognitiveImpairmentImpairment
DementiaDementia
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&Man ools himsel!
He prays or a long lie"
yet he ears an old age!#
hinese !roverb
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Dementia casesdouble every 20 years
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$unction
Age
Deinite AD
%robable AD
Mild cognitive impairment
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Mild cognitiveimpairment
Amnestic
Mild cognitiveimpairmentMultiple domainsslightly impaired
Mild cognitiveimpairment
&ingle non'memory domain
Al(heimer)s disease
Al(heimer)s disease
* normal aging
$rontotemporal dementiaLe+y body dementia
%rimary progressive aphasia
%ar,inson)s disease
Al(heimer)s disease
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Mild CognitiveIm%airment&MCI'
Criteria:
•Memor" com%laint
•Normal general cognitive (unction•Normal activities o( dail" living
•Memor" im%aired (or age
•Not demented
-ID./
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De)nition Dementia
•A decline o( intellectual (unction incom%arison ith %atient’s %reviouslevel o( (unction#
•*evere enough to cause im%airmento( social and %ro(essional activities
•+e,ected on decline on AD- and IAD-
•.suall" associates ith /ehavior changes#
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Area involves indementia
!"#I$I
!#
%EHA&I!R
ADL
(#$I!#
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01 To be earlier: potential beneits
• !btain a))ro)riate treatment earlier• Hel) t*e +amily to understand and acce)t
• inancial and le,al )lans -*ile com)etent
•Enable t*e )atient and +amily to ma.e li+estyle c*oices
• Induce better ad*erence and mana,ement o+ ot*er medical
conditions
• $a.e a))ro)riate ste)s to )revent in/ury drivin,1 -ea)ons
• "et ,reater access to *el) -it*in t*e *ealt*care system and
-it*in communities
from Cummings, 2011
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Dia,nosis
%ASED !# LI#IAL 3(D"ME#$
$y)e o+ dementia can be de4nedenou,* certainty t*rou,*5
•linical )atterns o+ dementin,
illness•Doin, a))ro)riate dementia-or.6u)
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Ste)s in Dementia 7or.6u)
• 0istor" ta1ing &ollateral source 2%atient'
• 3h"sical e4amination
• Mental status e4amination
• +elevant la/orator" and (ollo u%
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ollateral Source
• .suall" the s%ouse or an adult child#
• ###5/servations /" the collateralsource correlate /etter ithdementia than sel(6re%ortedcom%laints hich correlate more ithde%ression#
• A/sence o( collateral source seriousl"com%romises dementia diagnosis
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History $a.in,
Consists o(
•Neuro/ehavioral histor"
•7eneral medical histor"
•7eneral neurological histor"
•3s"chiatric histor"
• To4ic! nutritional 8drug
histor"
•9amilial histor"
dementia or not
3ossi/le underl"ingetiolog" orother conditionassociatesith dementia
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#eurobe*avioral History$a.in,
As. t*e collateral source
*%eci)call" as1 a/out changes : &A;C'
, o,nitive +unction: memor" %ro/lems!
orientation! language! e4ecutive (unction!%ersonalit"8a%ath"
, *an,e o+ be*avior
, De,ree o+ inter+erence -it* ADL and IADL
En<uire a/out: , )rst s"m%toms
, time o( onset
, nature o( illness
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Im)airment in Memory
*"m%toms:
•+e%etitive <uestions or conversations!
•Mis%lacing %ersonal /elongings!•9orgetting events or a%%ointments!
•7etting lost on a (amiliar route
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Im)airment in Lan,ua,e
• Involve s%ea1ing! reading! riting
• Di=cult" thin1ing o( common ordshile s%ea1ing! hesitations> s%eech!s%elling and riting errors
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Im)airment &isual s)atial 8abilities
*"m%toms:
•Ina/ilit" to recognize (aces orcommon o/?ects or to )nd o/?ects indirect vie des%ite good acuit"
•Ina/ilit" to o%erate sim%le im%lementsor orient clothing to the /od"#
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Dyse9ecutive +unction
Im%aired reasoning and handling o(com%le4 tas1s! %oor ?udgment @s"m%toms
•%oor understanding o( sa(et" ris1s
•ina/ilit" to manage )nances
•%oor decision6ma1ing a/ilit"•ina/ilit" to %lan com%le4 or se<uentialactivities
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*an,es in )ersonality :c*aracter
Im%aired motivation! initiative
*"m%toms:
•increasing a%ath" 2 loss o( drive•social ithdraal
•decreased interest in %revious
activities
%e*avioral and
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%e*avioral and)syc*olo,ical sym)toms
o+ dementia %;SD%e*avioural observation
•3h"sical aggression! screaming! restlessness!agitation! andering! culturall" ina%%ro%riate
or se4ual a//erants /ehaviours
;syc*osocial intervie-
•Disinhi/ition! hoarding! cursing and
shadoing•An4iet"! de%ression! hallucination anddelusions#
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;*ysical E9amination
• 7eneral %h"sical e4amination
• Neurological E4amination:
, Increased IC3
, 9ocal Neurological de)cit:
• 7ait! motor 2 sensor" de)cit
• A/normal muscle tone 2 movement
and %rimitive re,e4es
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o,nitive Screenin, $est
• Considering o( %racticalit"
• A /rie( screening test (or cognitiveim%airment that can /e %er(ormed inB minutes or less is easierincor%orated into dail" %ractice thana com%rehensive /ut time consuming
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%rie+ 8 !b/ectiveScreenin, $ests
;atient e9amination
•Cloc1 Draing Test &CDT'##############################
•*hort ;lessed Test &*;T'################################6B’•A//reviated Mental Test ## 6B’
•Mini Mental *tate E4amination &MM*E'#######B6’
•Montreal Cognitive Assessment &MoCA'###### FB6F’
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;syc*ometric $estin,
• Are not /" themselves diagnostic#
• 0el% in diagnosis /" %roviding<ualitative assessment o( mental(unction and the %attern o(involvement#
• 0el% in longitudinal assessment o(deterioration or im%rovement ithtreatment
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Laboratory Dia,nostic7or.6u)
%asic5
•%
•%S1 liver and renal
+unction tests•$*yroid stimulatin,*ormone $SH
•Serum %<2
Ancillary5• EE"• S analysis
• Serolo,y +orsy)*ilis
• HI& testin,• Heavy metal
screen
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NE.+5IMA7IN7
• *tructural M+I
, 0i%%ocam%us
, Entorhinal corte4
• 9unctional Imaging
, M+*
, (M+I
, 3ET8*3ECT
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Dia,nosis o+ AD
DSM6I&= A;A1 <>>?5
•7radual onset 2 %rogressive decline in:
, Memor" G at least one o( the:
, H A &A%hasia! A%ra4ia! Agnosia '
, D"se4ecutive (unctioning
•Im%airment in social and %ro(essional
activities! can’t /e e4%lained /" an" otherneurological! %s"chiatric! s"stemic orsu/stance6induced or onl" occur in delirium#
i +
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$ri,,ers o+ #on6ADDia,nosis
• 5nset JB "#o> sudden onset! cognition,uctuation! ra%id %rogression
• #eurolo,ic abnormalities earl" in coursee#g# involuntar" movement! (ocal de)cits!
gait distur/ance! ata4ia! seizures• %;SD earl" in course: visual hallucination!
disinhi/ition! mar1ed a%ath"! socialconduct
• #euro)syc*olo,ical )ro4le earl" incourse: %rominent a%hasia! mar1ed de)citin attention! e4ecutive (unction! visualagnosia
i@ i l
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ommon Di@erentialDia,nosis
• D-; &Dementia -e" ;od"'
• 3DD &3ar1inson Disease Dementia'
• 9T-D &9ronto6Tem%oral -o/eDementia'
• VaD &Vascular Dementia'
• 5thers
D-; Clinical Diagnosis
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D-; Clinical Diagnosis&Revised criteria III
2005)• Dementia ith %rominent de)cits inattention! e4ecutive (unction! andvisuos%atial a/ilit"#
• Core (eatures &to core (eatures:%ro/a/le D-;> one (or %ossi/le D-;': , 9luctuating cognition ith %ronounced
variations in attention and alertness
, +ecurrent o( ell (ormed and detailedvisual hallucinations
, *%ontaneous (eatures o( %ar1insonism
Clinical Diagnosis
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Clinical Diagnosis&Revised criteria III
2005)•*uggestive (eatures , +EM slee% /ehavior disorder , *evere neurole%tic sensitivit" , -o do%amine trans%orter u%ta1e in /asal
ganglia demonstrated /" *3ECT or 3ETimaging
•3ro/a/le D-;: or more core (eatures Gor more suggestive (eatures•3ossi/le : i( or more suggestive(eatures
t t l
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ronto6tem)oraldementia
Core diagnostic (eatures
•A Insidious onset and ,radual)ro,ression
•;# Earl" decline in social inter%ersonalconduct
•C# Earl" im%airment in regulation o(
%ersonal conduct•D# Earl" emotional /lunting
•E# Earl" loss o( insight
t t l
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ronto6tem)oraldementia
*u%%ortive diagnostic (eatures
A %e*avioral disorder ,# Decline in %ersonal h"giene and grooming
,F# Mental rigidit" and in,e4i/ilit"
,B Distractibility and im)ersistence
,? Hy)erorality and dietary c*an,es
,C ;erseverative and stereoty)edbe*avior
, (tiliation be*avior
t t l
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ronto6tem)oraldementia
;# *%eech and language# Altered s%eech out%ut
,a# A s%ontaneit" and econom" o( s%eech
,/# 3ress o( s%eech
F# *tereot"%" o( s%eech
H# Echolalia# 3erseveration
# Mutism
t t l
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C# 3h"sical signs
•# 3rimitive re,e4es
•F# Incontinence•H# A1inesia! rigidit"! and tremor
•# -o and la/ile /lood %ressure
ronto6tem)oraldementia
t t l
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Dementia ith:
•;ehavioral distur/ances 2 aLectives"m%toms
•*%eech disorders
•3h"sical signs o( %rimitive re,e4es
•Incontinence•A1inesia and rigidit"
ronto6tem)oraldementia
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&ascular dementia
Dementia ith:
•Evident o( cere/rovascular disease
•A clear tem%oral relationshi% /eteendementia and cere/rovascular disease
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VaD
Hac*ins.i Isc*aemic Score
•A /rie( clinical tool hel%(ul in the“/edside$ diLerentiation o( the
commonest dementia t"%es! Dementiao( Alzheimer’s T"%e &AD' and VascularDementia &VaD'
•A cut6oL score (or AD and O (orVaD has a sensitivit" o( PQR and as%eci)cit" o( PQR &Morone" QQO'
./01/2
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./01/2
Item #o Descri)tion &alue
< A/ru%t onset F
2 *te%ise deterioration
B 9luctuating course F
? Nocturnal con(usion
C 3reservation o( %ersonalit"
De%ression F *omatic com%laints
G Emotional incontinence
> 0istor" o( h"%ertension
<0 0istor" o( stro1e F<< Associated atherosclerosis
<2 9ocal neurological s"m%toms F
<B 9ocal neurological signs F
Hachins,i Ischaemic &core
AD &s &aD
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AD &s &aD
AD VaD
Neuro trans!itter de"ect He!od%na!ic de"ect&e!ale predo!inance 'ale predo!inance
(radual onset Abrupt onset
Stead% deterioration Step)ise deterioration*
"luctuating courseBP nor!al H%pertension
No histor% o" stroke Histor% o" stroke
(lobal decline in cogniti+e
"unction
&ocal neurological s%!pto!s
and signs
,nlikel% to respond to
treat!ent
'a% respond to a drug )hich
!odi"ies !icrocirculation and
enhance cerebral tissue
per"usion
A good teacher is a perpetual learner
;otentiall Re ersible
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;otentially ReversibleDementia
# 0"%oth"roidismF# 3ernicious anemiaH# Chronic *u/dural 0ematoma
# CN* in(ections: T;! Cr"%tococcal! viral!0IV! s"%hilis
# TumorsJ# Normal %ressure h"droce%halusO# Drug into4icationP# 0eav" metal %oisoning
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Features suggesting reversibilityFeatures suggesting reversibility
• *horter duration o( illness
• *u/cortical t"%e o( dementia
•Moderatel" severe distur/ance• Sounger age o( onset
• 3rominent gait distur/ance
• .rinar" d"s(unction• 9ocal neurological signs
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A1in To Dementia
• Delirium
, Acute onset
, 9luctuating course , Autonomic distur/ances
, 3reci%itating (actors li1e in(ection!
meta/olic and drugs
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MMSE
• *creening test to %rovide /rie(!o/?ective measure o( cognitive (unction
• Administered in B6 minutes! scoresrange (rom B to HB
• “.se(ul in <uantitativel" estimating theseverit" o( cognitive im%airment$
• “.se(ul in seriall" documentingcognitive change in serial $
Di@erent co,niti e domains
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Di@erent co,nitive domainstested
In seven categories:•5rientation to time %oints•5rientation to %lace %oints
•+egistration o( three ords H %oints•Attention and calculation %oints•+ecall o( three ords H %oints•-anguage P %oints
•Visual construction %oint
Total HB %oints
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MMSE
ut6o@ Score
•F6HB no cognitive im%airment•P6FH mild cognitive im%airment
•B6O severe cognitive im%airment
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MMSE
"ood )oints o+ t*e MMSE
•Most idel" acce%ted screening test
•7ood internal consistenc"
•7ood test6retest relia/ilit"•0igh validit": good sensitivit" and good
•s%eci)cit"
•Correlates ell ith other screeningtests e#g# cloc1 draing test and *hort;lessed test
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MMSE
Limitation
•Con(ounded /" age! education andculture
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loc. Dra-in, $est D$
•A sensitive measure o(:
•Visuo6s%atial (unction andconstructional %ra4is#
•0igher ordered cognitive a/ilities li1ethe conce%t o( time
Can hel% diLerentiate /eteen aconstructional vs# conce%tual %ro/lem
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?6;oint Scorin, Met*od
#olan KA1 Mo*s R1 <>>?
•Dras closed circle %oint
•3laces num/ers in correct %ositions %oint
•Includes all F correct num/ers %oint
•3laces hands in correct %osition %oint
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CDT: E9am)les
3atients ere instructed to dra in thehands at tent" minutes a(ter eight
•9igure A: /" a normal elderl" control
•9igure ;6E: %atients ith dementia
Inter)retation5 linical
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Inter)retation5 linical /ud,ment
• A lo score & H' indicates the need(or (urther evaluation to source outother evidences o( im%airment or
correlation ith other tests
The role o( medications in
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The role o( medications inthe management o(
dementia# Cure disease
F# 3revent disease or dela" onset
H# *lo %rogression o( disease
# Treat %rimar" s"m%toms egmemor"
# Treat secondar" s"m%toms egde%ression! hallucinations
Medications to treat %rimar"
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Medications to treat %rimar"s"m%toms
• cholinesterase inhi/itors:
, done%ezil
, rivastigmine
, galantamine
• memantine
Ch li i hi/i
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Cholinesterase inhi/itors• these drugs sto% the /rea1don o(
acet"lcholine hich is an im%ortantneurotransmitter in memor" and cognition
• all sho modest im%rovement in cognition
and (unction! and /ehavioural s"m%toms• res%onse: 8H im%rove! 8H sta/ilise! 8H
have no res%onse
• do not %revent %rogression o( underl"ing
disease
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Cholinesterase inhi/itors
• done%ezil &Arice%t'
, given once dail"! dosage o( mg to Bmg
• rivastigmine &E4elon' , given tice dail"! dosages o( Hmg to
Fmg
• galantamine &+emin"l'
, given once dail"! dosages o( Pmg toFmg &can also /e given tice dail"'
.se o( cholinesterase
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.se o( cholinesteraseinhi/itors
• need s%ecialist diagnosis o( AlzheimersDisease! and a MM*E score o( B to F#
• need to sho an im%rovement on MM*E o(
F %oints to continue medication on 3;*• side eLects 6 nausea! vomiting! diarrhoea!
dizziness! headache! muscle cram%s
• use care(ull" i( gastric ulcer! heart disease!
chronic lung disease %resent
.se o( cholinesterase
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.se o( cholinesteraseinhi/itors
• arn against unrealistic e4%ectations
• atch (or return o( insight leading tode%ression or an4iet"
• sto%%ing o( medication:
, unacce%ta/le side eLects
, lac1 o( res%onse to medication
, late stages o( the disease
Memantine &E/i4a'
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Memantine &E/i4a'
• glutamate is a transmitter in the /rain that
is aLected /" Alzheimers Disease• memantine /loc1s the %athological eLects
o( a/normal glutamate release! and allos/etter (unction o( the im%aired /rain
• indicated (or moderate to severe AD
• trials sho sloing in cognitive and(unctional decline and decrease in agitation
in treated grou% com%ared to %lace/o
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Memantine
• can use ith other AD medications• side eLects 6 headaches! dizziness
• do not use in 1idne" disease or seizure
disorders• dosage: start ith mg dail" and
increase toBmg tice dail"
• %rivate scri%t 6 not on the 3;*• costs a%%ro4 JB8month
Medications to treat
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Medications to treatsecondar" s"m%toms
• man" %eo%le ith dementia develo%s"m%toms such as agitation! aggression!de%ression! delusions! hallucinations!
slee% distur/ance and andering
• antide%ressants:
, s%eci)c serotonin reu%ta1e inhi/itors
&citalo%ram! sertraline'
-ID./
Medications to treat
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• anti%s"chotics:
, t"%ical anti%s"chotics &halo%eridol'
, at"%ical anti%s"chotics &ris%eridone'
, modest eLect on s"m%toms
, atch (or side6eLects
• mood sta/ilisers:
, anticonvulsants &car/emaze%ine'
Medications to treatsecondar" s"m%toms
auses
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auses*everal com%eting h"%otheses:
*oliner,ic *y)ot*esis6Caused /" reduced s"nthesis o(acet"lcholine
6Destruction o( these neurons causesdisru%tions in distant neuronal netor1s&%erce%tion! memor"! ?udgment'
Amyloid *y)ot*esis6A/normal /rea1don> /uildu% o( am"loid
/eta de%osits6Damaged am"loid %roteins /uild to to4iclevels! causing call damage and death
$au *y)ot*esis6Caused /" tau %rotein a/normalities
69ormation o( neuro)/rillar" tangles
Ris. actors
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Ris. actors
• 5/esit"• 0igh /lood %ressure• 0ead trauma• 0igh cholesterol• ;eing AmericanU
, 0igher rates in• a%anese6Americans than a%anese• A(rican6Americans than A(ricans
• De%ression• -oer rates in highl" educated
, ;ene)cial conse<uences o( learningand memor"
;ossible ;rotective
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;ossible ;rotectiveactors
• EducationThe ability of the brain to change suggests tosome that staying mentally active as you agemay help to maintain healthy brain synapses. A 2002 study reported an association betweenfrequent participation in cognitivelystimulating activities (such as reading, doing
crossword puzzles, visiting museums and areduced ris! for Alzheimer"s.• E9ercise
#owers ris! of high blood pressure and other ris!factors associated with Alzheimer$s
• Alco*ol onsum)tion
%en who consume one to three drin!s of alcohol per day cut their ris! of developing the diseaseby nearly half. Among women, however, the ris!was reduced by only &'. The type of alcohol hadno eect on the results. )ut further study isneeded. *n the meantime, e+perts do notrecommend drin!ing alcohol to fend o Alzheimer"s disease.
AD 2esearch: Managing &ymptoms
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3etween 41 to 516 of people with " eventually develop
behavioral symptoms including sleeplessness wanderingand pacing aggression agitation anger depression and
hallucinations and delusions# $xperts suggest these general
coping strategies for managing difficult behaviors:
AD 2esearch: Managing &ymptoms
• 7tay calm and be understanding#
• 3e patient and flexible# "on’t argue or try to convince#• cknowledge re+uests and respond to them#• %ry not to take behaviors personally# 8emember: it’s
the disease talking not your loved one#
$xperts encourage caregivers to try non-medical copingstrategies first# 9owever medical treatment is often available if
the behavior has become too difficult to handle# 8esearchers
continue to look at both non-medical and medical ways to help
caregivers#
Management o Al(heimer)s Disease
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Management o Al(heimer s Disease
Manage
cognitive
symptoms
Manage B%&D
&upport
patient3amily
Increased
4uality o
lie or
patient andamily
%h l i / ti AD
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%harmacologic /ptions or AD
• ognitive enhancers W . classes
• holinesterase inhibitors (h$s)
• ;<"-receptor antagonist W "o not cure the disease or reverse cognitive
impairment
W an improve cognition and functional ability
W 8educe the rate of decline 5-. months (h$s)
W "elay in nursing home placement was 4-.
months (h$s)
Behavioral and %sychological
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y g
&ymptoms o Dementia 5B%&D1
• pathy• "epressive symptoms
• nxiety
• gitation/irritability/aggression
• !sychotic symptoms
W "elusions
W 9allucinations
• "isinhibition
• $uphoria
• =oss of appetite
• 7leep disturbances
• 7tereotyped
behaviors (eg
pacing wanderingrummaging picking
%ampi et al#Clinical Geriatrics.
.1>5:?-?@#
Managing B%&D
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g g
• dentify triggers W Observe symptom timing and fre+uency
W =ook for environmental triggers eg noise lighting
W nvestigate potentially treatable causes eg pain
• <ake ad*ustments
W ddress medical causes
W dapt environment
W dapt caregiving• <odify as needed
Managing B%&D
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g g
Nonpharmacological Interventions
• Ase the &0 8s'Brepeat reassure redirect• 7implify the environment task routine
• nticipate unmet needs
• llow ade+uate rest between stimulating
events
• Ase cues
• $ncourage physical activity
• Other interventions
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• !8OC"$ =<DA$% $;C8O;<$;%
%O <A9 7%<A=%O; ; A7$ %7%8O!98$%O;
• !8OC"$ O;77%$;% 8OA%;$
!$8EO8< "=s % 7<$ %<$ $9 "F
CO" 9;G$7 ; 8OA%;$ O8 $;C8O;<$;%• 8$77A8$ ;" $H!=; E8$DA$;%=F
"O ;O% 8GA$ I%9 %9$ !%$;%
• !8O%$% 7E$%F
!%$;% % ;8$7$" 87J OE "$;%7
• $=<;%$ EE$;$ E8O< %9$ "$%
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• !8OC"$ %C%$7 %O "7%8% %9$ !%$;% E8O< ;!!8O!8%$
3$9CO8
• <;%; 8$GA=8 8OA%;$
• A7$ !%$;$ ;" A;"$87%;";G
• <;%; =< DA$% $;C8O;<$;%
• A7$ 7<!=$ =$8 IO8"7 ;" 7$;%$;$7
• GC$ E8$DA$;% !87$ ;" 8$77A8;$
• A7$ %OA9 ;" O%9$8 EO8<7 OE ;O;C$83= O<<A;%O;
• A7$ 8$=%F O8$;%%O;
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Conclusion
• Early diagnosis enables prompt and effectivemanagement, yields better quality of life for
patients and caregiver
• Neuroimaging especially MRI scan is widelyused in clinical setting now
• !iomar"er especially C#F study $as been
included in researc$ diagnostic criteria, butnot yet recommended for general clinical use,furt$er validation is eagerly awaited
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• %$e core of all assessment in dementia care iscareful enquiry and attentive listening, and
• %$ere is no substitute for a clinical interview by a trained clinician
• !y doing appropriate wor"&up and recogni'ingt$e clinical pattern, most of t$e cause of
dementia especially (l'$eimer)s diseasedementia can be determined on enoug$certainty
Conclusion