Prognosis of Parkinson Disease

7/23/2019 Prognosis of Parkinson Disease

http://slidepdf.com/reader/full/prognosis-of-parkinson-disease 1/44

Prognosis of Parkinson Disease

Risk of Dementia andMortality: The Rotterdam

Study

Oleh : Ni Putu Witari

Pembimbing : dr AAA MeidiarySpS

ARCH NEUROL/OL !"# AU$

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Background :

'he pre(alen)e *+ P, i- e.pe)ted t* in)rea-e a-p*pulati*n- *rldide age0 1n-ight int* thepr*gn*-i- i- there+*re de-irable

P, ha- been a--*)iated ith an in)rea-ed ri-2 *+de(el*ping dementia 3 a redu)ed li+e

e.pe)tan)y

Most prognostic studies have been hospitalbased0 n*t repre-entati(e *+ the generalp*pulati*n

4a)2gr*und

andOb e)ti(e



6

• e(en in p*pulati*n7ba-ed -tudie-# a)*n-iderable pr*p*rti*n *+ )a-e- *+ P,remain undiagn*-ed hen case

nding relies on medical recordsonly and no population screening isdone

• An*ther i--ue i- hether the pr*gn*-i-

*+ patient- ith P, (arie- ith APOEgenotype, because pre(i*u- -tudie- ha(e

-h*n )*n8i)ting re-ult-4a)2gr*und

andOb e)ti(e



Objective :•

'* e(aluate hether Par2in-*ndi-ea-e i- a--*)iated ith anin)rea-ed ri-2 *+ dementia and death

•

+urtherm*re in(e-tigated t* hate.tent redu)ed -ur(i(al in patient-ith P, i- due t* their higher ri-2 *+dementia#

• and hether APOE genotypeinfuences prognosis

Ob5e)ti(e



Methods

A pr*-pe)ti(e p*pulati*n7ba-ed )*h*rt -tudy

am*ng 9;< -ub5e)t- && year- and *lder

At ba-eline =>%7><? and" +*ll*7up (i-it-

=><7>@ and >97>?# parti)ipant-ere

inter(ieed and underent e.ten-i(e

phy-i)ale.aminati*n

Meth*d-



6

• the )*h*rt a- )*ntinu*u-ly

m*nit*red +*r ma5*r di-ea-e*ut)*me- and m*rtality thr*ugh

)*mputeried lin2age t* general pra)titi*ner-Bmedi)al le-

• All parti)ipant- ga(e their in+*rmed)*n-ent# and the Medi)al Ethi)-

C*mmittee *+ the Era-mu- Medi)alCenter# R*tterdam# the Netherland-#appr*(ed the -tudy

Meth*d-



A!M!"# O$ PD A"DD!M!"#%A•

At ba-eline and +*ll*7up# e u-ed a "7-tage pr*t*)*l t* identi+y -ub5e)t- ith P,and a <7-tage pr*t*)*l t* a--e-- dementia

• All parti)ipant- ere -)reened +*r-ympt*m- *+ par2in-*ni-m# and th*-e h*-)reened =D? re)ei(ed a -tru)tural d.*r2up u-ing the Unied Par2in-*nB-

,i-ea-e Rating S)ale• Per-*n- -u-pe)ted *+ ha(ing P, ere

e.amined by a neur*l*gi-t

Meth*d-



6

• P, a- d. i+ at lea-t " par2in-*nian

-ign- ere pre-ent *r i+ at lea-t > -ignhad impr*(ed thr*ugh medi)ati*n and

all )au-e- *+ -e)*ndary par2in-*ni-m had beene.)luded

• Age at d. *+ P, and H*ehn and ahr -)ale-)*re +*r di-ea-e -e(erity ere a--e--edand (eried +r*m medi)al re)*rd-

•

C*gniti(e -)reening *+ all parti)ipant-a- per+*rmed ith the MMSE and $eriatri)

Mental State -)hedule

Methods



6

• Sub5e)t- h* =D? ere e.amined ith the

Cambridge E.aminati*n *+ Mental,i-*rder- in the Elderly

• 1+ the re-ult *+ thi- e.aminati*n a-in)*n)lu-i(e# a neur*p-y)h*l*gi-t

per+*rmed +urther e.aminati*n and# i+p*--ible# MR1 a- d*ne

• Final d. a- made a))*rding t* Diagnosticand Statistical Manual o Mental Disorders,Revised 3rd Ed criteria

• 'he )*mputeried -ur(eillan)e -y-tem)*ntinu*u-ly pr*(ided additi*nalin+*rmati*n *n b*th P, 3 dementia6

Methods



A!M!"# O$ MO&#A'%#( A"D

)O*A&%A#!• M*rtality until Ganuary ># "%%%# a- a--e--edthr*ugh )*ntinu*u- m*nit*ring *+ themuni)ipal addre-- le- and )*mputeriedrep*rt- +r*m general pra)titi*ner- *n the death- *+

parti)ipant-

• 1n+*rmati*n *n highe-t attained edu)ati*nalle(el# -m*2ing habit-# medi)ati*n u-e# andli(ing -ituati*n a- *btained during the

ba-eline inter(ie

• APOE genotyping was perored *nba-eline -ample-

Methods



#+D( POP+'A#%O"

•

At ba-eline# ,-,- participants underentneur*l*gi) -)reening

• -- a- P, =prevalent PD?# during +up#an*ther ,. ere identied =incident PD?

• All !! parti)ipant- ere +up t* -tudym*rtality ri-2

• '* e.amine the ri-2 *+ in)ident dementia# ee.)luded parti)ipant- ith in)*mplete ba-eline)*gniti(e -)reening =n!? and th*-e diagn*-ed

a- ha(ing dementia at ba-eline =n<>"?# 'here-ulting -tudy -ample *+ !!&> n*n dementedparti)ipant- )*mpri-ed 9" pre(alent and !9in)ident P, )a-e-

Methods


http://slidepdf.com/reader/full/prognosis-of-parkinson-disease 12/44Re-ult



o e oe n an a rstaging

tage 0 : N* -ign- *+ di-ea-e

tage 1 : Unilateral di-ea-etage 123 : Unilateral plu- a.ial in(*l(ement

tage 4 : 4ilateral di-ea-e# ith*ut impairment *+balan)e

tage 423: Mild bilateral di-ea-e# ith re)*(ery *npull te-t

tage 5 :Mild t* m*derate bilateral di-ea-eI -*mep*-tural in-tabilityI phy-i)ally independent

tage 6 : Se(ere di-abilityI -till able t* al2 *r -tanduna--i-ted

tage 3 : Wheel)hair b*und *r bedridden unle--aided



DA#A A"A'(%

• HR- +*r in)ident dementia and m*rtalityere )*mputed by mean- *+ C*.pr*p*rti*nal haard- regre--i*n analy-i-all*ing +*r delayed entry# ith age a-the time -)ale and P, a- a time7dependent )*(ariate

• M*del- ere initially ad5u-ted +*r age and-e.6 P*tential )*n+*under- e additi*nallyad5u-ted +*r ere -m*2ing =e(er (- ne(er?#nur-ing h*me re-iden)y# anti par2in-*nianmedi)ati*n u-e# and edu)ati*nal le(el =primaryedu)ati*n *nly (- m*re than primary edu)ati*n?6

Methods



6

• 4e)au-e *+ the ide range *+ di-ea-edurati*n *+ pre(alent P, )a-e- at thetime *+ in)lu-i*n in the -tudy# eper+*rmed -eparate analy-e- +*r )a-e-

ith di-ea-e durati*n J and K & year-• Within the latter gr*up# e +urther

l**2ed -eparately int* th*-e ith K "

year-B durati*n =hen)e in)ludingin)ident P, )a-e-? and in)ident P,)a-e- *nly

Methods



6

• '* e(aluate hether and t* hat e.tentredu)ed -ur(i(al in patient- ith P, i-

e.plained by an in)rea-ed ri-2 *+dementia# e ad5u-ted +*r *))urren)e *+dementia in a time dependent +a-hi*n

• All analy-e- ere -tratied *n APOEgenotype =</<# @# and "I "/@ e.)luded? t*e.amine p*tential m*di+ying ee)t- *npr*gn*-i-

•

Median -ur(i(al +r*m diagn*-i- a-)al)ulated by the aplan7Meier meth*d• All analy-e- ere per+*rmed ith SAS -*+tare

=(er-i*n ;6"I SAS 1n-titute 1n)# Cary# NC?6

Methods



Re-ult-

•

Fup a- (irtually )*mplete =?until Ganuary ># "%%%

• 'he t*tal +up time a- @; !%!

per-*n7year- =*(erall mean# !6year-?

• 'he mean H*ehn and ahr -)ale

-)*re *+ pt- ith pre(alent P, ="6<?and in)ident P, =>6;? a- relati(elyl* )*mpared ith pre(i*u- -tudie-

Re-ult



o e oe n an a rstaging

tage 0 : N* -ign- *+ di-ea-e

tage 1 : Unilateral di-ea-etage 123 : Unilateral plu- a.ial in(*l(ement

tage 4 : 4ilateral di-ea-e# ith*ut impairment *+balan)e

tage 423: Mild bilateral di-ea-e# ith re)*(ery *npull te-t

tage 5 :Mild t* m*derate bilateral di-ea-eI -*mep*-tural in-tabilityI phy-i)ally independent

tage 6 : Se(ere di-abilityI -till able t* al2 *r -tanduna--i-ted

tage 3 : Wheel)hair b*und *r bedridden unle--aided



&%7 O$ D!M!"#%A

• At ba-eline# "" parti)ipant- ith P, 3@ *+ th*-e n* P, ere diagn*-ed a-ha(ing dementia

•

,emented pt- ith P, ere -igni)antly*lder than th*-e ith*ut dementia6

• Free dementia )*h*rt at ba-eline# ">=>&6>? *+ the >< P, and <>; =@6?*+ the !&>" parti)ipant- ith n* P,de(el*ped dementia during +up

Re-ult



6

Re-ult



6

• 'he pre-en)e *+ P, a- a--*)iated ith a-igni)antly in)rea-ed ri-2 *+ dementia =HR#

"6;%I & C1# >697@6<;I #able 48

• Re-ult- ere -imilar a+ter additi*nalad5u-tment- and +*r -ubgr*up- *+ di-ea-e

durati*n at ba-eline6 H*e(er# re-tri)tinganaly-e- t* *nly in)ident P, )a-e- re-ultedin a higher e-timate =HR# @69@I & C1#"6@76%"?

• ,i-ea-e durati*n did n*t -eem t* ae)tdementia ri-2 ithin P, )a-e- =HR in)rea-eper year# %6!I & C1# %6;@7>6%?

Re-ult



6

• 'he a--*)iati*n *+ P, ith in)ident

dementia a- m*re pr*n*un)ed inparti)ipant- ith at lea-t > APOE !"allele =/&9 ,24.I & C1# <6%97

>"6;"?# and e-pe)ially in th*-e)arrying at lea-t > APOE !# allele$ HR, !"#$% &'( )*, @6@!7@%6!@?#

)*mpared ith </< )arrier-

Re-ult



MO&#A'%#( &%7 • ,uring +up# % =&@6"? *+ the >!! P, pt-

and >!"< ="<6? *+ the !;%< parti)ipant-ith*ut P, died

• Median -ur(i(al a+ter diagn*-i- *+ P, a-6> year- =& C1# 96@7>%6 year-?6 O(erall#

P, a- a--*)iated ith a -igni)antlyin)rea-ed m*rtality ri-2 =HR# >6;<I & C1#>6@97"6"!? HR- )*n-i-tently de)rea-ed henthe analy-e- ere -euentially re-tri)ted t*

pt- in h*m P, a- diagn*-ed m*rere)ently

Re-ult



Re-ult



6

• 'he ee)t *+ P, *n -ur(i(al a- n*tdierent +*r men and *men# *r by-trata *+ APOE genotype

• +itin PD cases, m*rtality ri-2 a-in8uen)ed by di-ea-e durati*n =HR

in)rea-e per year# >6%<I & C1# %67>6%9? andby *))urren)e *+ dementia =HR# "6;&I

& C1# >6997@6!"?6

Re-ult



)omment• 'he -trength- *+ thi- -tudy are it-

p*pulati*n7ba-ed nature# -ie# andalm*-t )*mplete +up

• Ca-e a-)ertainment +*r P, and dementia

a- en-ured thr*ugh in7per-*n in-tead *+re)*rd7ba-ed -)reening meth*d-

• 'he u-e *+ -tri)t d. )riteria enhan)ed d.a))ura)y# 3 )*ntinu*u- m*nit*ring *+

parti)ipant- a+ter d. enabled u- t* re(i-ed. *n the ba-i- *+ additi*nal in+*rmati*n

C*mment



6

• 4e)au-e e +up pre(alent a- ell a-

in)ident P, )a-e-# e )*uld e(aluatethe ee)t *+ di-ea-e durati*n *npr*gn*-i- and p*tential bia- inpre(alent )*h*rt-

• An Q ri-2 *+ dementia a--*)iated ithP, ha- repeatedly been rep*rted# ith

relati(e ri-2- (arying +r*m >69 t* &66 Our

e-timate *+ a "6;7time- in)rea-ed ri-2 i-relati(ely l* 0

C*mment



6

the l* a(erage d- -e(erity# hi)h

re-ulted +r*m *ur -)reening meth*d-# thr*ugh hi)he identied a large number *+ pre(i*u-lyunre)*gnied patient- ith mild P,

e )*n-ider it li2ely that patient-ith P, h* agreed t* parti)ipate at

ba-eline had +eer )*gniti(e )*mplaint-and thu- a l*er ri-2 *+ +uture dementia than n*nre-p*nder-# hi)h may ha(e led u- t* undere-timatethe ri-2 +*r pre(alent )a-e-

C*mment



6

• We +*und that the ee)t *+ P, *n

dementia ri-2 a- m*re pr*n*un)ed inparti)ipant- )arrying at lea-t > APOE@ allele and remar2ably -tr*ng inth*-e )arrying at lea-t > APOE !#

allele

• APOE, coded or by te APOE gene# i-a p*lym*rphi) pr*tein abundant in the

brain that i- in(*l(ed in lipid tran-p*rt#immun*regulati*n# and m*dulati*n *+)ell gr*th

C*mment



• F*r Alheimer d-# the APOE !" alleleis an establised ris- actor, wereaste " allele i- )*n-idered pr*te)ti(e

• 1n )*ntra-t# a re)ent meta7analy-i-)*nrmed the repeatedly *b-er(eda--*)iati*n *+ the " allele ith an

in)rea-ed ri-2 *+ P,# hile re-ult- +*rthe @ allele ere in)*n-i-tent

C*mment



6

• A -igni)ant p*-iti(e a--*)iati*n ith*))urren)e *+ dementia in patient-ith P, ha- been *b-er(ed +*r b*th

the @ allele and the " allele hi)h-ugge-t- that the APOE gene mightm*di+y the ri-2 *+ dementia

a--*)iated ith P, I the e.a)t me)hani-mby hi)h APOE genotype *r ap*lip*pr*tein Ei-*+*rm- in8uen)e the ri-2 and )*ur-e *+ P, i- -tillun)lear6

C*mment



6

• 'he *(erall m*rtality HR *+ >6; e

*b-er(ed i- in line ith gure- +r*m *ther

-tudie-# ranging +r*m >6& t* "69# them*rtality HR a- higher +*rpatient- ith l*nger d- durati*nand relati(ely l* +*r nelydiagn*-ed in)ident )a-e- 0 it t-

pre(i*u- *b-er(ati*n- that m*rtality rate- in pt-

ith P, ere n*t in)rea-ed )*mpared ith th*-ein )*ntr*l- in the r-t year- *+ +up and dieredm*re a- time -in)e diagn*-i- in)rea-ed

C*mment



6

• Apart +r*m the ee)t *+ aging# d-durati*n thu- -eem- t* in8uen)e

MR in P,# 3 dieren)e- in the)*mp*-iti*n *+ -tudy p*pulati*n-

ith re-pe)t t* mean and range *+ durati*n *+ P,

may lead t* dierent e-timate- *+m*rtality ri-2

C*mment



6

• Sin)e e *b-er(ed that mean H*ehnand ahr -)ale -)*re- ere)*n-i-tently higher in )ateg*rie- *+

l*nger d- durati*n# the ee)t *+ d-durati*n *n MR might re8e)t theee)t *+ d- -e(erity 0 '* )*rre)tly

e(aluate pr*gn*-i- a+ter P, d.# pr*-pe)ti(e-tudie- *+ in)ident )a-e- are reuired

C*mment



a5ian riti- 44

16 Apa2ah bu2ti ttg pr*gn*-i- ini(alid

>6Apa2ah ter2umpul -ebuah -ampelpa-ien yang 5ela- dan repre-entati+pada -uatu titi2 =bia-anya dini? dlmper5alanan penya2it

0 a# deni-i penya2it 5ela-#pr*-pe)ti(e ba-ed p*pulati*n -tudy

E4M



6

"6 Apa2ah pengamatan pa-ien )u2uppan5ang dan leng2ap

0 mengingat rata7rata u-ia parti-ipan-aat ba-eline# lama pengamatandapat di2ata2an )u2up untu2menge(alua-i 2e-udahan demen-ia

dan 2ematian

0Pengamatan pada -tudi ini leng2ap

E4M



Re-ult

6



<6 Apa2ah 2riteria 2e-udahan yang

*bye2ti+ diterap2an -e)ara blind 0Untu2 menge)il2an bia- pada

2e-udahan dimen-ia# peneliti -dh

mengguna2an 2riteria -pe-i2 yang 5ela- dan menerap2annya 2e -eluruhparti-ipant

0Untu2 m*rtalita-# 2e-udahan -dh 5ela- -)r *bye2ti+

E4M



@6 Apa2ah dila2u2an penye-uaian

untu2+a2t*r pr*gn*-i- yang penting

0 a# Haard rati* di2al2ula-i dgn

anali-aC*. pr*p*rti*nal haard

regre--i*n

E4M



e-impulan : alid

116 Apa2ah bu2ti ttg pr*gn*-i- inipenting

>6Seberapa be-ar 2e-udahan ini ter5adiuntu2 5ang2a a2tu yang lebih pan5ang

Mengingat u-ia parti-ipant# 2e-udahan

demen-ia dan m*rtalita- a2an mening2at dg ma-a pengamatan lebih pan5ang

E4M



6

"6 Seberapa per-i-i e-tima-i

pr*gn*-i-

E-tima-i pr*gn*-i- penelitian ini

)u2up 2uat dengan C1 %6%&

e-impulan : penelitian ini

penting

E4M



1116 Apa2ah 2ita dapat menerap2anbu2ti ttg

pr*gn*-i- yang alid dan Pentingini 2epada pa-ien 2ita >6 Apa2ah pa-ien dalam penelitian ini

-erupa dgn pa-ien 2ita

Se)ara dem*gra mung2in ada-edi2it perbedaan# tapi 2ara2teri-ti22lini- pa-ien Par2in-*n di 1nd*ne-ia

dapat di2ata2an -erupa denganpa-ien di l*2a-i penelitian#

E4M



6

"6 Apa2ah bu2ti ini a2an mempunyai

pengaruh yang penting -e)ara 2lini-thd 2e-impulan 2ita ttg apa yang perluditaar2an atau diberitahu2an 2epadapa-ien 2ita

a

e-impulan : Ha-il penelitian inidapat diterap2an

E4M



6

'erima a-ih

Prognosis of Parkinson Disease

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