Demented by Ageing

8/7/2019 Demented by Ageing

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A bb re vIa tIo ns U se d:C DR c lin ica l d em en tia ra t ingv s v en tric ula r s co reA D A lzhe lm e r d ise aseM ID m u ltiIn fa rc t d em en tia5 5 su lca l s co re

NEURORAD IOLOGY

39 1

C om p ute d T om o gra ph y a nd A gin g o f th e B ra in Charles P . H ughes , M .D . and Mohk ta r G ado , M .D .

C lin ica l assessm en t o f p a tien ts w ith va ry ing deg rees o f dem en tia d isc losed no s ig n if ican tn eu ro log ic d isease . Com pu ted tom ography (C T ) stu d ies o f these pa tien ts p e rm itted th em easu rem en t o f ven tricu la r and su lca l s izes w h ich d id no t appa ren tly re la te to m en ta l s ta -tus , bu t w h ich d id re la te to age .IND EX TERM S : H e a d , com pu ted to m o gra p hy , 1 (0 ).12 1 1 # { 1 4 9 }o m pu te d to m ogra p hy , ind ica tio ns #{149}g ing #{149}emen t iaS B ra in , v olu me #{149}S ku ll, o the r fu n da m en ta l ob se rva tio n , 1 [0 ].9 1 9 )R ad io logy 1 39 :3 91 -3 96 , M ay 198 1

H E s tud y o f ce reb ra l a tro phy w ith c om p u ted tom og ra -4 p hy (C T ) ha s been o f in te re st s in ce the in trodu ction o f

th is m e thod fo r b ra in im ag ing in 197 4 . W h ile s h rin kag e a ndlo ss o f b ra in s ubs tan ce had be en c lin ic a lly (1 ) an d pa tho -lo g ic a lly (2 , 3 ) ass oc ia te d w ith d em e n tia , C T w a s ex pe cte dto a id in the id en tific a tio n o f p re sen ile a nd s en ile de m en tia .L im ita tions o f th is m e th od inc lud ed p oor reso lu tion o fc o rtic a l s u lc i-pa rtic u la rly w ith ea rlie r m a ch ine s-an d ,u n til rec en tly , the ina b ility to d is ting u is h g ray an d w h item a tte r. In ad d ition , fo r h igh e r cra n ia l sec tio ns, the us ua lp lane o f C T de m on stra tes the fno n top an ie ta l co nve x ity bu tno t the su rfac es o f th e tem po ra l lo bes w h ere p ro m in en tA lz he im e r d is ea se (A D ) is o fte n p res en t.

A num ber o f s tud ies ad dres se d the n orm a tiv e da ta fo rs ub jec ts o f va rious ag es (4 -1 0 ), an d the e ffe c t o f thep re sen ce o f dem en tia (1 1 - 1 8 ). S om e se em to agre e tha tv en tricu la r s iz e incre as es w ith ag e . T h is inc reas e and ag em ay be re la ted to th e p res enc e o f de m en tia , th oug h anu m be r o f e xc e p tio n s p re c lu d e s u ch a c o n c lu s io n . In are ce n t le tte r, F o x (1 9 ) re fe rre d to h is g ro u p s e xp e rie n cea n d e m ph a s ize d th a t, w h ile C T w a s in va lu a b le in ide n tify in ga g e d p a tie n ts w ith p o te n tia lly tre a ta b le ca u s es o f d em e n tia ,fin d in g s o f c e re b ra l a tro p h y co u ld no t b e in te rp re te d . W ea tte m p te d to e xa m in e th is h yp o th e s is , u s in g a re la tive lyu n se le c te d g ro u p o f p a tie n ts re fe rre d fo r C T .

M A T E R IA L S A N D M E T H O D SF ro m O c to b e r, 1 9 7 7 to M ay , 1 9 7 9 , o n e o f u s (M G ) e x-

a m in e d C T sca n s o f h o s p ita lize d p a tie n ts a t le a s t 6 5 ye a rso f a g e . M G e xc lu d e d ca se s w ith p ro b a b le ce re b ra l in -fa n c tio n s o n m a s s le s io n s , a n d p ro b a b le co m m u n ic a tin g

\. h yd n o ce p h a lu s , us in g cr ite ria e s ta b lish e d h e re (2 0 ). T h ere m a in in g p a tie n ts w e re re fe rre d to o n e o f u s (C P H ) w h oe xa m in e d th e pa tie n ts w h ile th e y w e re s til l in th e h o sp ita l.H ere , m ore pa tien ts w ere e xc lud ed if c lin ica l inv estiga tionind ica ted s ign ific an t h is to ry o f ce reb rov as cu la r d is eas e ,hea d trau m a, a lco ho lism o n pre v io us in trac ran ia l su rg e ry .P a tie n ts w e re a lso e xc lu d e d if th e ir m e d ica l c o n d itio n s

pre c luded e xa m in a tio ns fo r ad equ a te m e n ta l s ta tus , o r ifthey ha d bee n d is ch a rge d fro m the h osp ita l be fo re c lin ic a lin te rv ie w s. S o m e p a tie n ts w e re re fe rre d fro m th e N e u -ro logy an d P sy ch ia try se rv ices; m os t re fe rra ls cam e fromthe In te rn a l M ed ic ine D ep artm en t.

T he c lin ica l inve stiga tion c ons is ted o f a re v iew o f a llpe rtin en t rec o rds , p a tie n t in te rv iew s a nd , w h ere ap pno -pn ia te , in te rv iew s w ith co lla te ra l sou rces o f in fo rm a tion .T a k in g a ll in fo rm a tion in to ac cou n t, the p a tie n t w as g iv ena C lin ic a l D e m en tia R a tin g (C D R ), dev e lo ped and s tan -da rd ized by m em bers o f the D em en tia S tud y G roup a tW ash ing to n U nive rs ity .

T h is g rou p recogn ize d d e fic ien c ies in ex is ting s ys tem sw h ich tried to use e ithe r n um e rica l sc o rin g o f fu nc tion a lab ilitie s o r ps yc hom etric tes ts to de te rm ine the ex is tenc ean d de gree o f de m en tia in a pa tien t. A s a res u lt, a g lob a lra t ing w a s de v is ed to c a te go rize a nd sco re s ix fu nc tion s:m e m o ry (w h ic h re c e ive s th e m o st e m p h a s is ), o r ie n ta tion ,jud gm e n t an d pro b le m so lv in g , inv o lv em en t in com m u n itya ffa irs , ho m e life and h obb ies , an d pers ona l ca re . A pa tie n tc an rece ive a s co re fo r ea ch ca tego ry : 0 , no rm a l fu nction ;0 .5 , que stiona b le dy sfun ction ; 1 .0 , m ild dysfu nction ; 2 .0 ,m ode ra te dy sfunc tion ; 3 .0 , s ev e re dy sfu nction . A p a tie n tc an re ce iv e a g lo b a l ra tin g o f d e m e n tia o n th e sa m e b a s is(TA B L E l) .2 In u npu b lishe d w o rk a t W as h in g ton U n iv e rs ityi t w a s fo u n d th a t m o s t p a tie n ts ca n b e u n a m b ig u o u s lyp lac ed in one c a te go ry o r ano the r a nd th a t in te r-ra te r re -l ia b ility is h ig h (co rre la tio n c o e ffic ie n t 0 .8 7 ). T h e S h o rtP o rtab le M e n ta l S ta tus Q ue stionn a ire (21 ) w a s a ls o ad -m in is te red to a nu m b er o f th e pa tie n ts . F o rm a l p syc ho -m e tric tes ts w ere no t us ed , bu t the us e o f g loba l ra tin gs

1 F rom th e D e pa rtm e n t o f N e u ro lo g y a n d N e u ro lo g ic a l S u rg e ry an d T he E dw ard M allin ck rod t In s titu te o f R ad io log y , W ash in g to n S ch o o l o f M ed ic in e ,S t. Lou is , M is sou ri. R e ce ive d Ju ly 3 1 , 1 98 0 , a nd acc ep ted N ov em be r 2 5 . bc

2 D e ta ils a bo u t the u se o f th is ra ting s ca le c an be ob ta ine d o n req ue s t. (S ee rep rin t ad d ress .)


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F o u r lin e a r m e a su re m e nts o f th e ve n tricu la r s ys te mw e re m a d e (F ig . 2 ). T h re e o f th e se m e a su re m e n ts w e reta ke n fro m th e im ag e a t th e le ve l o f th e fo n a m e n o f M o n ro :A th e w id th o f th e th ird v e n tr ic le ; B th e s u m o f th es ho rte s t d is ta n ce s b e tw e e n th e ca u d a te n u c le u s a n ds ep tu m p e llu c id u m ; C = th e w id th o f th e la te ra l ve n tric le sju s t a n te r io r to th e fo ra m e n o f M o n n o . D th e w id th o f th en a rro w e st p a rt o f th e b o d ie s o f th e la te ra l ve n tr ic le . T h ew id e s t in te n p a n ie ta l d is ta n c e w a s m e a su re d fro m th e im a g es h o w in g th a t p a rt o f th e ve n tr ic le . A ve n tr icu la r sc o ne (V S )w a s o bta in e d w ith th e fo llo w in g e q ua tio n :

VS = x 1 0 0 . (1 )A su lc a l s co n e (S S ) w a s a lso o b ta in e d fro m th e su m o f

th e fo u r la rg e s t s u lc i s ca n n e d in th e up p e r th re e s e c tio n s .A ll o f th e m e as u re m e n ts w e re m a de in m ill im e te rs , u s in ga co m p a ra to r (a m a g n ify in g le n s w ith a n e tic u le ), a n d p o -la n o id pr in ts . A ccu ra cy w a s ju d g e d to b e w ith in 0 .5 m m .

S ta tis tic a l m an ip u la tio n s o f th e d a ta w e re p e rfo rm edw ith th e S ta tis tica l A n a lys is S ys te m p a ck a ge , ve rs io n79.1.

RESULTS

R ou g h ly 4 7 % o f e a ch ra ce a n d s e x w a s m ild ly , m o d -e ra te ly o n s e ve re ly d e m e n te d (F ig . 3 ). A s re fle c te d in th eC D R , n o a p p a re n t re la tio n sh ip e x is te d b e tw ee n m e a su re so f b ra in m a ss u se d , a n d m e n ta l s ta tu s . V S w a s p lo tte da g a in s t C D R (F ig . 4 ). T h o se w ith n o d e m e n tia w e re g ro u p e dwith tho s e fo r w h om th e d ia g n o s e s w e re q u e s tio n a b le .Simi la r ly , n o s ig n ific a n t re la tio n s h ip e x is te d b e tw e e nm e a s u re s o f m e n ta l fu n c tio n a n d S S (F ig . 5 ). E x a m in a tio no f th e d a ta fo r d is tr ib u tio n s b y se x y ie ld e d a p p a re n tly the

R a c e SexF ig . 1 . B a r g rap h , sh ow in g th e d is tr ibu tio n o f

pa tie n ts by ra ce an d sex . B = B la ck , W = W hite , M= M a le , F = Fe m a le .

39 2 C H A R L E S P . H U G H E S A N D M O H K T A R G A D O M ay 19 8 1

3 A 1 00 5 E M I de d ica te d h ea d sca n ne r w as us ed .

TABLE I: T H E C L IN ICA L DEM ENT IA R AT IN GC o g n itive Q ue s tion ab leF un c tion N o D em en tia D em en tia M ild D e m e n tia M od era te D em en tia S ev e re D e m e n tia

O n l y (C D R 0 ) (C D R = 0 .5 ) (C D R = 1 .0 ) ( C D R = 2 .0 ) ( C D R = 3 .0 )M e m o ry N o l o s s , o r s lig h t

incons tan tfo rge t fu lness

M i ld , c o ns is te n tfo rge t fu lness(ben ignfo rge t fu lness )

M ild to m od era telo ss ( hi nd er se ve ry da y a ct iv iti es )

S ev e re los s (o n lyh ig hly le arn edm ate ria l re ta in ed )

S e ve re lo ss (o n lyf ragmen tsr e m a in )

O rien ta tio n 10 0% 10 0 % S om e tro ub le w ithtim e a nd g e og -r ap hy ; o rie nte dfo r p e rso n an du su ally p la ce

N o sen se o f tim e ;o ften d iso rie n te d top la ce ; o rie n te d tope rson

M ay b e lo s t in h om e;on ly o rien ta tion tope rso n m ay re m ain

Ju dg em en t a n d N o rm a l; d oe s w e ll O n ly d ou b tfu l U su a lly m a in ta in ed M a rke d im pa irm en t T o ta lly inc ap a b lep ro b lem im pa irm e n t on so c ia l ba s is ;s o lv in g m o de ra te

im p a i r m e n tInvo lv em en t in In de p en de n t fun c tio n O n ly d ou b tfu l o r M ay a pp ea r n o rm a l, N o ind e pe nd e n t N o in de pe n de n t

c om m un ity a t u su a l le ve l m ild im pa irm e n t bu t is u na b le to fu nc tion ou ts id e fun c tio n ou ts id ea ffa irs fun c tio n

independen t lyh o m e ho m e

H om e life an d W e ll m a in ta in ed M a in ta ine d o r M ore d ifficu lt O n ly s im p le N o s ign ific an t fu nc tionhobb ies s ligh tly im pa ire d a c tiv it ie s a ba n do ne d fu nc tion s m ain -t a m e d

o uts id e p ers on ala reaP e rso na l ca re C a p ab le o f

se l f -ca reC ap a b le o f

se l f -ca reC apa ble o f s elf-ca re ;

n ee ds p ro m pt in gN e e ds so m e h e lp

w ith d res s in g an dhyg iene

N e ed s m u ch he lp ; m a yb e i nc o nt in e nt

p e rm itte d th e in c lu s io n o f a w id e v a rie ty o f p a tie n ts ,ra n g in g fro m th e n o rm a l to th e se ve re ly d e m e n ted fo rw h o m c o g n itiv e m e a su re s g a ve no m e a n in g fu l re s u lts .

T h e yo u n g e s t o f th e 1 0 0 p a tie n ts in th is s tu d y w e re6 5 -y e a rs -o ld . T h e m e a n a g e w a s 75 .4 6 .9 y e a rs . T h ed is tr ib u tio n o f m e n an d w o m e n w a s n e a rly e q u a l, b u t ap re p o n de ra n ce o f w h ite p a tien ts re fle c te d th e in pa tie n tp o p u la tio n -a t B a rn e s H o s p ita l (F ig . 1 ). A ll p a tie n ts w e resca n n e d 3 u s in g a n im a ge m a trix o f 1 6 0 X 1 6 0 p ixe l e le -m e n ts a n d a se c tio n th ickn e s s o f 8 m m . F o r th is s tu d yc on tra s t m a te ria l w a s n o t u s ed .

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V ol. 1 39 C O M P U T E D T O M O G R A P H Y A N D A G IN G O F T H E B R A IN

A LL B W F MF ig . 3 . B a r g ra ph , s ho w ing th e d is tr ib u tio n o f c lin ica l d e -

m e n tia b y race a nd se x . (C O R -1 , 2 , 3 ) B B la ck , W W hite ,F Female, M = Ma le .

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Fig . 4 . G rap h show ing th e re la tio nsh ip o f the VS and CO R . Th osepa tie n ts w ith no de m e n tia o r q ue s tio na b le d e m e n tia (C D R 0 o r 0 .5 ,re sp ec tiv e ly ) a re g rou ped to ge the r. E ach b ar ind ica te s on e stand arddev ia t ion .

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0 5 2 3C D R

F ig . 5 . G rap h sh ow in g th e re la tion sh ip o f 55 a n d C D R . T h ose pa -tie n ts w ith n o d em en tia o r q ue s tio na b le de m e n tia (C D R 0 o r 0 .5 ,re sp ec tive ly ) a re g ro u pe d to ge the r. E a ch b a r ind ica tes on e s ta nd arddev ia t ion .

F ig . 2 . D ia g ra m sh ow in g c ro ss sec tion s a t th e lev e ls o f the fo ram eno f M on ro ( le ft), a nd the b od ie s o f the la te ra l v en tric les (rig h t) . A th ewid th o f th e th ird ve n tric le . B th e su m o fth e sh o rte s t d is ta n ces be -tw ee n the ca ud a te n uc leu s a nd th e an te r io r en d o f th e se p tu m p e ilu -c idu m o n b o th s ide s . C the w id th o f th e la te ra l v en tric le s ju s t a n te rio rto th e fo ra m e n o f M on ro . 0 the n arrow e s t pa rt o f th e b od ie s o f th el at er al v en tr ic le s .

sa m e re su lts (F ig s . 6 a n d 7 ), th o u g h a d iffe re n c e se e m e da p p a re n t in th e re la tio n sh ip o f s ex to V S .

A re la tio n s h ip b e tw e e n m e a su re s o f b ra in m a s se s a n dm e n ta l fu n c tio n s co u ld n o t b e e s ta b lish e d . T h e re w a s a

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3 9 3 N eu ro ra d io

d iffe re n ce w ith re sp e c t to a g e . T h e V S a n d S S w e re e x-a m in e d in re la tio n to th e C D R fo r o ld er a n d yo u n g e r p a -tie n ts (F ig s . 8 a n d 9 ). P a tie n ts w e re g rou p e d b y a g e : th o s e6 5 to 7 4 y e a rs , a n d th o se 7 5 to 8 4 . O n ly a fe w o f th e p a -tie n ts in o u r se r ie s w e re o ve n 8 5 -y ea rs -o ld . A co n s is te n tlyla rg e r m e a n v e n tric u la r s ize w a s n o te d in m e m b e rs o f th eo ld e n g ro u p in e a ch ca te g o ry o f m e n ta l fu n c tio n . A s im ila rfin d in g w a s se e n in m e a su re s o f su lc a l s ize in a ll b u t th em ild ly d e m e n ted p a tie n ts (C D R = 1.0).

T h e in te rre la tio n sh ip s o f V S , S S a n d a g e w e re a ls on o te d in th e s ta tis tic a l m a n ip u la tio n s o f d a ta fro m th e 1 0 0p a tie n ts . If th e e ffe c ts o f se x , ra ce a n d C D R w e re e lim i-n a te d , a g e g re a tly a ffe c te d th e V S (p 0 .0 0 9 ), a ndw ea k ly -b u t s till s ig n ifica n tly -a ffe c te d th e s u lca l sco re(p = 0 .0 4 3 ). If th e e ffe c ts o f se x , ra ce an d a g e w e ree lim in a te d , th e re w as n o s ig n ifica n t re la tio n sh ip b e tw e e nth e C D R a n d V S (p 0 .5 9 ) o r th e C D R a n d th e 5 5 (p0 .5 3 ). T h e re w a s n o s ig n ifica n t c o rre la tio n b e tw e e n th eve n tr icu la r a n d su lca l m e a su re s (p 0 .2 ).

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C D RF ig . 6 . G rap h sho w in g th e re la tio ns h ip o f th e V S a nd C D R fo r m en

and w om en . Pa tie n ts w ith no d em en tia o r q uestio nab le dem en tia (C DR= 0 o r 0 .5 , re sp ec tive ly ) a re g rou p ed tog e th e r. E a ch b a r re sp re se n tson e s tan da rd d ev ia tion .

39 4 C H A R L E S P . H U G H E S A N D M O H K T A R G A D O M ay 1981

90 8

80

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30 #{163} :Men, O:Wn20

10

D I S C U S S I O N

W h e n C T s ca n s d e m o n stra te la rg e r ve n tr icu la r sp a cea n d la rg e r ce re b ra l s u lc i, th e re is n o re a s o n to b e liev e th a tth e a p p a re n t lo ss o f b ra in su b s ta n c e is n o t re a l. T h is s tu d ysh o w s a co rre la tio n o f a d va n c in g a g e n o t o n ly w ith in -c re a s in g ve n tr icu la r s ize , b u t a lso w ith e n la rg in g s u lc i,th o u g h th e la tte r is s lig h tly le ss c on v in c in g . A t th e sa m etim e , s ta tis tic s d id n o t d is c lo s e a n in te rre la tio n s h ip b e -tw e e n d e m e n tia a n d e ith e r ve n tricu la r o n su lc a l s iz e . F u r-th e n m o re , th e re a re e x ce lle n t e xa m p le s -p re se n t a n d p a s t(1 2 )-n o t o n ly o f s ev e re ly d e m e n te d p a tie n ts w ith n orm a lve n tr ic le s a n d su lc i, bu t a lso o f n o n -d e m e n te d p a tie n ts w itha b n o rm a l v e n tric le s a n d su lc i.

S a tis fy in g e xp la n a tio n s fo r th e s e fin d in g s a re n o t y e ta va ila b le . W h ile s u b je c t to th e u su a l c ritic ism s o f c ro ss-se c tio n a l s tu d ie s , h o w e ve r, a n u m b e r o f in ve s tig a tio n s o np a tie n ts b o rn m o re th a n a c e n tu ry a p a rt d o su g g e st th a tb ra in w e ig h t d e cre a se s w ith a g e -a b so lu te ly , a n d inre la tio n to b o d y h e ig h t-p a rticu la r ly a fte r a g e 6 5 (2 2 -2 4).P e a rl (2 5 ) d e m o n stra te d th a t, in y o un g e r (2 3 to 3 0 y e a rso f a g e ) a n d o lde r (80 ye a rs o f a g e) p a tie n ts , th e va ria tio n so f b ra in w e ig h ts d iffe re d (1 ,0 0 0 to 1 ,8 5 0 g a n d 1 ,0 0 0 to1 ,4 5 0 g , re s p ec tiv e ly ). H e a lso o b se rve d th a t th e u p p e r a n dlo w e r lim its o f b ra in w e igh t (7 5 0 to 1 ,2 5 0 g ) w e re sm a lle rin th o s e w ith se n ile d e m e n tia .

E ffo rts to u n d e rs ta n d w h a t p a rt o f the b ra in is d isa p -p e a n in g h a v e b e e n fru s tra te d b y th e s ta tis tica l p ro b le m s

#{163}en

O W o m e n

C D RF ig . 7 . Gra p h sh ow in g th e re la tio nsh ip o f the 55 a nd C O R fo r m en

and w om en . P atien ts w ith no d em en tia o r qu est ion ab le d em en tia (C OR= 0 o r 0 .5 , re spe c tive ly ) a re g ro u p e d toge the r . E a c h b ar in d ica tes o nes ta nd ard d ev ia tio n.

e n co u n te re d in a tte m p tin g to d e te rm in e th e n u m b e r o f ce lls_3 in p a rts o f th e h u m a n b ra in . S e ve ra l s tud ie s , m ore re ce n t

th a n B ro d y s , te n d to co n firm th e la tte r s fin d in gs (2 6 , 2 7 )th a t in th e ce re b ra l co rte x th e n u m b e r o f ne u ro n s d im in -ish e s w ith a g e ; h o w e ve r, n o d e fin ite re la tio n s h ip c o u ld b ee s ta b lish e d b e tw e e n s uc h c e ll co u n ts a n d d e m e n tia , d e -sp ite a w id e sp re a d im p re s s io n o f n e uro p a th o lo g is ts th a ta los s o f n e u ro n s a cc o m pa n ie s v a rio u s d e m e n tia s . B ro d y(2 6 ) d id fin d , ho w e ve r, th a t ce ll lo ss va r ie d w ith a g e-ra n g in g fro m n o a p p a re n t lo ss in th e p o s tce n tra l g yru s toa 6 0 % lo ss in th e s up e rio r te m p o ra l g yru s .

M o rp h o lo g ic (2 8 ) a n d b io ch e m ic a l s tu d ie s (2 9 ) h av esu g g e ste d tha t d e nd n itic p ro ce ss e s a tro p h y w ith a g e a n dd e m e n tia . In ra ts th e e x tra ce llu la r sp a c e d im in ish e s w itha g e (3 0 ). T h is fin d in g is d ifficu lt to e x tra p o la te to o th e rsp e c ie s , b u t m a y s u g ge s t th a t th is s p a ce a lso c h a n g e s w itha g e .

T h e re fo re , s h rin k a g e o f th e b ra in w ith ag e p ro ba b lyin vo lv e s g ra y a n d w h ite m a tte r, a t le a s t in th e ce re b ra lh e m isp h e re s . C e rta in s tu d ie s h a v e su g g e s te d th a t va r io u sb ra in s te m nu c le i m a y n o t lo se c e lls w ith a g e (3 1 -3 4 ). T h isa n d B no d y s (2 6 ) fin d in g s a b o u t th e c e re b ra l co rte x s u g g e s tth a t su ch a tro ph y m a y b e fa r fro m u n ifo rm in v a rio u s p a rtso f th e b ra in . E v id e n ce n o w s u g g es ts th a t ce ll n u m b e r,d e n d n itic vo lu m e a n d e xtra ce llu la r sp a ce m a y d im in ish ing ra y m a tte r. H o w e ve r, little is k n o w n a bo u t a s im ila r p ro -ce ss in w h ite m a tte r, tho u g h it l ike ly d im in ish e s w ith a g e,to o , b e ca u s e v e n tr ic u la r s ize h a s b e e n re lia b ly co rre la tedw ith a g e . T h e re fo re , c e ll p ro c e sse s m u st d im in ish inre la tio n to lo ss o f th e c e ll b o d y . S in ce th e a bn o rm a litie sin A D a re u s u a lly w id e sp re a d , s u ch a p ro c e ss in o ld a g ep ro b a b ly w O u ld fu rthe r in c re a s e th e n o rm a lly o ccu rrin g lo sso f b ra in s u b s ta n ce . S e n ile d e m e n tia s ee m s a s so c ia te d w ithd e s tru c tiv e p ro c e sse s in the b ra in , in c o n tra s t to ce rta inb io ch e m ica l s to ra g e d ise a s e s w hich se e m to a d d b ra inb u lk in ch ild re n . H ow e ve r, th is c o rre la tio n b e tw e e n d e -m e n tia a n d b ra in a tro p h y h a s n o t re ce ive d co n v in c in g ra -d io lo gic co nfirm atio n.


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0 1 20. 5 C D RF ig . 8 . a ph s ho w in g th e re la tion sh ip o f th e V S an d C D R fo r

yo un ge r (65 to 7 4 -ye a r-o ld ) an d o ld e r (7 5 to 84 -ye a r -o ld ) p a tien ts . P a -tie n ts w ith no de m e n tia o r q ue s tio n ab le de m e n tia (C O R 0 o r 0 .5 ,resp e c tive ly ) a re g ro up ed to ge the r. E a ch b a r ind ic a te s o ne s ta n da rddeviation.

p la sm s o n h yd ro ce p h a lu s .

Vo l . 139 COM PU TED TOMOGRAPH Y AND AG ING O F TH E BRA IN 3 9 5 N eu ro ra d i

G o s lin g (1 ) us e d a ir e n ce p h a lo g ra p h y to d e m o n stra tea p p a re n t a tro p h y in 8 5 % of p r im a rily yo u n g e r p a tie n ts w ithd e m e n tia . H is w o rk a lso s h o w e d n o n -d e m en te d p a tie n tsw ith s o m e a tro p h y . H u ck m a n e t a !. (1 2 ) p e rfo rm e d th e firs tm a jo r C T stu d y o f th is su b je c t a n d s u gg e s te d th a t a co n -re la tio n e x is te d b e tw e e n a tro p h y a n d d e m e n tia , b u t n o te de xc e p tio n s . H o w e ve r, fu rth e r s tu d ie s (1 4) sh o w e d n o re -la tion s h ip b e tw e e n a tro p h y a n d E E G c h a n g e s, a n d fo u n dth a t th e s e ra d io lo g ic m e a su re m e n ts d id n o t p re d ic t m o r-ta lity in d e m e n te d p a tie n ts (1 5 ), w h ile c e rta in p sy ch o m e trica n d E E G ch a n g e s d id .

M o re re ce n tly , K a sz n ia k e t a !. (1 8 ) s tu d ie d 7 8 o ld e rp a tie n ts w ith d e m e n tia . W h e n th e e ffe c ts o f a g e a n d e d -u ca tio n w e re ta ke n in to a c co u n t, th e re s u lts su g g e s te d th a tce re b ra l a tro p h y id e n tifie d b y C T m e th o d s co rre la te dso m e w h a t w ith ce rta in co g n itiv e fu n c tio n s (v e rb a l re ca ll,s e n te nc e p ro d u c tio n ), b u t n o t w ith o th ers (p ra x is , o n ie n -ta tio n , d ig it sp a n , v isu a l m e m o ry ). S im ila r re s u lts w e reo b ta ine d b y E a rn e s t e t a !. (1 6 ) in a s tu d y o f 5 9 n o n -d e -m e n te d p a tie n ts o ve r 6 0 -y e a rs -o ld , th o u g h s ig n ifica n t e f-fe c ts o f a g e w e re se e n h ere , a s w e ll. In a s tu d y o f 4 3 o lden ,d e m e n te d p a tie n ts , d e L e o n et a !. (1 7 ) u se d a s lig h tly d if-fe re n t C T m e th o d to d e m o n stra te s o m e re la tio n sh ip b e -tw e e n ve n tr icu la r a n d su lca l e n la rg e m e n t a n d p e rfo rm a n ceo n p syc h o m e tric te s ts . W ith o u t u s in g m e a su re m e n ts , n a -d io lo g is ts ra n k e d sca n s a cc o rd ing to in cre a s ing ve n tricu la ra n d su lca l s ize s . S ig n ifica n t co rre la tio n s w e re n o te d b e -tw e e n th e se ra n k in g s a n d co g n itive d a ta .

C D RF ig . 9 . G ra ph s ho w ing the re la tion sh ip o f the 55 an d C D R fo r

you n ge r (65 to 7 4 -yea r-o ld ) a nd o ld e r (75 to 84 -ye a r-o ld ) pa tie n ts . P a -tien ts w ith n o de m e n tia o r q u es tion ab le d em en tia (C O R 0 o r 0 .5 ,respe ctive ly ) a re g rou ped tog ether . E ach b ar ind ic a te s o ne s tan da rddeviation.

P a tie n ts w ith d e m e n tia u s u a lly c a n n o t b e d ia g n o se dac cu ra te ly in life ; h o w e v e r, a u top s ie s h a ve o fte n su g g e s te dth e p a th o lo g ic d ia g n o s is o f A D (3 , 3 5 ) if th e fo llo w in gm e ta b o lic a n d ne u ro lo g ic co n d itio n s ca n b e e xc lu d e d :P a rk ins o n d ise a se , H un tin g to n d ise a se , in fe c tio n o f th ec en tra l n e rvo u s sys te m , b ra in tu m o r, co m m u n ic a tin g h y-dro ce p h a lus , pro g re s s ive su p ra n u c le a r p a lsy , m a jo r ce -n e b ra l va s cu la r d ise a s e , a n d m u ltip le sc le ro s is . O f th ep a tie n ts w ith d e m e n tia , a b o ut 5 0 % w ill h a v e a n a n a to m icd ia g n o s is o f A D , 1 0 % to 1 5 % w ill h a ve m u ltiin fa rc t d e -m e n tia (M ID ), 1 0 % to 1 5 % w ill h av e a m ix tu re o f A D a n dM ID , a n d th e re s t w ill h a v e a n in d e fin a b le p a th o lo g ic d is -ea s e , o r a ra re va sc u la r, d e g e n e ra tiv e , m e ta s ta tic p ro c e ssn o t d ia g n o se d in life . S e v e n p e rc e n t o f th e se p a tie n ts m a yh a ve id io p a th ic p a rk in so n ism , th o u g h a re ce n t s tu d y su g -g e s te d th a t a m a jo rity o f th e se p a tie n ts w ith P a rk in so nd is e a se m a y h a ve p ro m in e n t A D a t a u to p sy (3 6 ).

W h ile C T ca n d e m o n stra te a g e -re la te d a tro p h y o f th eb ra in , c h an g e s p e cu lia r to g lo b a l d e m e n tia s c a n n o t b ere lia b ly p re d ic te d , p re se n tly , b y a s in g le s tu d y o f o n e p a -tie n t. H o w e ve r, th e se ch a n g e s a n d a g e h a ve a p ro n o u n ce dre la tio n sh ip -a c o n s ta n t fin d in g in s tu d ie s o f th is k in d-th o u g h w e fo u n d n o a p p a re n t re la tio n sh ip b e tw e e n d e -m e n tia a n d C T m e a su re s . D em e n tia in o ld a g e m a y re la teto : ve ry su b tle d iffe re n c e s in bra in m a s s ; ch a n g e s in sy -na p s e s , o r o n ly in ce rta in critic a l a re a s ; p rim a rily b io -ch e m ica l p ro ce s se s ; o r, m o re like ly , a co m b in a tio n o fth e se fa c to rs . T o th is e n d , m o re q ua n tita tive C T m e th o d s(3 7 , 3 8 ), se r ia l s tu d ie s o f th e s a m e p a tie n ts o ve r tim e , o rpo s s ib ly so m e a p p lic a tio n o f p o s itro n e m iss io n to m o g ra -ph y m a y b e tte r d e m on s tra te the s ig n ific a n t ch a n g e s re la te dto d e m e n tia in e ld e rly p a tie n ts . H o w e ve r, in th e in itia l a s -se ss m e n t o f a p a tie n t w ith d em e n tia , C T sca n n in g re m a in sva lu a b le a s a m e a n s to e x c lu d e ce re b no v a scu la n d is e a seo n s in g le o u t po te n tia lly tre a ta b le le s io n s s uc h a s n e o -


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39 6 C H A R L E S P . H U G H E S A N D M O H K T A R G A D O M ay 1 981

A C K N O W L E D e M E N T : T h e co n s id e rab le h e lp o f D r. Le o na rd B erg an do th e r m em b e rs o f the D e m e n tia S tu dy (ou p o f W ash ing ton U n ive rs itya nd o f D r. R ich a rd To ra ck o f the D e p artm e n t o f P a th o log y is a pp re -c ia ted . D r. R e im u t W ette o f the D iv is ion o f B ios ta tis tic s a ss is ted in thes ta tis tica l a na ly s is . P a tti V es se ll w a s o f c on s id e rab le h e lp in thep rep ara tio n o f the m an usc rip t.C ha rl es P . H ug he s, M .D .D ep a rtm en t o f N eu ro lo gyW ash in g to n U nive rs ity S ch oo l o f M ed ic in e6 00 S ou th E u c lid A ve nu eBox 8111S t. L ou is , M O 6 31 1 0

R E F E R E N C E S1 . G o s lin g R H : A sso c ia tio n o f de m e n tia w ith rad io lo g ica lly d em -

o n s tra te d c e re b ra l a trop hy . J N e uro l N e u ros u rg an d P s ych ia t18:129-133, May 1955

2 . M cM e ne m e y W H : Th e d em en tia s an d pro g ress ive d ise a se s o fth e b a sa l ga ng lia . [In ] B lac kw oo d W , M cM e ne m e y W H , M e ye rA , e t a l, e ds : G re en fie ld s N e urop a th o log y . B a ltim ore , W illiaman d W ilk in s , 19 6 7 , pp 5 20 -58 0

3 . T om lin so n B E , B le sse d G , R o th M : O bse rva tio ns o n th e b ra in so f de m e n te d o ld pe op le . J N e u ro l S c i I 1 :2 05 -24 2 , S ep 1 97 04 . G y ld en s te d C , K o s te lja n e tz M : M ea su re m e n ts o f th e n o rm a l

he m isph e ric su lc i w ith co m pu te r to m ogra p hy : a p re lim ina ry s tu dyon 44 adults. Neuroradiology 10:147-149, 19 Dec 1975

5 . B arron S A , Jac ob s L , K in ke l W R : C ha ng e s in s ize o f n o rm a lla te ra l v en tric les d u rin g a g in g d e te rm ine d by c om pu te rize d to -mography: Neurology 26:101 1-1013, Nov 1976

6 . G aw le r J , D u B o u lay G H , B u ll JW , e t a l: C om pu te rize d tom og -ra ph y (th e E M I sca n ne r): a c om pa ris on w ith pn e um o e nce p ha -lo g ra p hy a nd ve n tricu lo g ra p hy . J N euro l N euro su rg P sy ch ia try3 9 :2 03 -21 1 , M a r 19 76

7 . H ah n F JY , R im K : F ro n ta l v en tricu la r d im en s ion s o n n orm a lco m p u te d tom og ra ph y . A JR 1 2 6 :5 9 3 -5 9 6 , M ar 1 9 76

8 . G y lde n s ted C : M e a sure m e n ts o f the n o rm a l ve n tricu la r sys te ma nd h em isp h eric su lc i o f 10 0 a du lts w ith co m pu te d to m og rap hy .N eu ro rad io lo gy 14 :18 3 -19 2 , 3 1 D e c 1 97 7

9 . H a ug G : A ge an d s ex de p en de n ce o fth e s ize o f n o rm a l ve n tr ic leso n co m p u te d to m o gra ph y . N eu ro rad io lo gy 1 4 :2 01 -20 4 , 31 D e c1 9 7 71 0 . Ja co by R J , L e vy R , D a w so n JM : C om pu ted tom og ra ph y in thee ld e r ly : I. T he n orm al p op u la tion . B r J P s ych ia try 1 36 :24 9 -25 5 ,M ar 1 98 0

1 1. Ja co by R J , Le vy R : C om pu ted tom og rap h y in the e ld e rly . 2 .S e n ile de m e n tia : d iag no s is a n d fu nc tion a l im p a irm e n t. B r JP s ych ia try 1 36 :25 6 -26 9 , M ar 1 9 80

1 2 . H uck m a n M S , F ox J , T op e l J : T h e va lid ity o f c rite ria fo r thee va lu a tio n o f ce re b ra l a trop hy b y co m p u te d to m o g rap h y . R a-d io lo gy 11 6 :8 5 -92 , Ju l 1 97 5

1 3 . R o be rts M A , C a ird F l: C o m p u te riz ed tom og rap h y an d in te lle c tua lim pa irm en t in th e e lde rly . J N e uro l N e urosu rg P sych ia try 3 9 :9 86 -98 9 , O c t 1 97 6

1 4 . S te fo sk i 0 , B e rge n D , F ox J , e t a l: C o rre la tio n be tw e en d iffus eE E G a bn orm a lit ies an d ce re b ra l a trop hy in se n ile de m e n tia . JN eu ro l N e u ros u rg P syc h ia try 3 9 :7 51 -7 55 , A u g 19 761 5 . K a szn ia k A W , F o x J , G a nd e ll D L , e t a l: P re d ic to rs o f m o rta lityin p re sen ile an d s en ile d e m en tia . A n n o f N eu ro l 3 :2 46 -2 52 , M a r1 9 7 8

16 . E arne s t M P , H e a to n R K , W ilk in so n W E , e t a l: C o rtic a l a tro ph y ,ven tric u la r e n la rge m en t a nd in te lle c tua l im pa irm en t in the a ge d .N eu ro lo gy 29 :1 13 8- 1 14 3, A ug 1 979

17 . de L eo n M J , F e rris S H , B lau I, e t a l: C o r re la tion s be tw e e nc om pu te rise d to m o gra p h ic ch a ng es a nd be ha v iou ra l de fic its ins en ile d em en tia . La nc e t 2 :8 59 -86 0 , 20 O c t 1 9 79

18 . K asz n iak A W , G a rro n D C , F ox JH , e t a l: C e re b ra l a tro ph y , E E Gs lo w ing a ge , ed uc a tio n , an d c og n itive fu n c tio n ing in s usp e c teddem e n tia . N eu ro logy 2 9 :127 3-127 9 , S e p 1 97 9

19 . F ox JK , K asz n iak A W , H u ckm an M : C om pu te rize d to m o gra p h icscann ing no t v ery he lp fu l in d em en tia -n or in c ra niop ha ryn gio ma .N EngI J Med 300:437, 22 Feb 1979

2 0 . G ad o M H , C o lem an R E , L e e K S , e t a l: C o rre la tion be tw e e nc om pu te rize d tra n sax ia l to m ogra ph y a nd ra d io nu c lide c is te rn -o g rap hy in d em e n tia . N e uro lo g y 2 6 :5 5 5 -5 6 0 , J un 1 9 76

21 . P fe iffe r E : A s ho rt po rta b le m en ta l s ta tu s q ue s tio n na ire fo r th ea sse ssm en t o f o rga n ic b ra in d e fic it in e ld e rly pa tie n ts . J A mGer ia t r S oc 2 3 :4 33 -4 41 , O c t 19 75

2 2 . H a nd m a nn E : U b e r d es h irng e w ich t d es m e n che n . A rch iv F u rA na t un d E n tw icke lu n gsg e sch ich te 8 :1 -4 0 , 19 0 6

2 3 . A pp e l F W , A p pe l E M : In tra c ra n ia l va ria tio n in the w e igh t o f th eh u m a n bra in . H u m a n B io lo gy 1 4 :4 8 -68 , F e b 19 4 2

2 4 . D e ka ba n A S : C h an g es in b ra in w e ig h ts d u rin g the s pa n o f hu m a nlife : re la tio n o f b ra in w e igh ts to b od y h e ig h ts a n d b od y w e ig h ts .A n n N e u ro l 4 :3 45 -3 56 , O c t 1 9 78

2 5 . P ea rl R : B io m e tric a l s tud ie s o n m a n . I. V a ria tio n a nd c o rre la tio nin b ra in -w e ig h t. B iom etrika 4 :13 -1 04 , J un 1 9 05

2 6 . B ro d y H : O rg a n iza tion o f ce reb ra l co rtex ; s tud y o f a g ing in theh um an c erb ra l co rtex . J C o m p N eu ro l 1 0 2 :5 1 1 -5 5 6 , A pr1 9 5 5

2 7 . T e rry R d, F itzg e ra ld C , P e ck A , e t a l: C o rtica l ce ll c ou n ts in se n iled e m en tia . A bs tra c ts o f th e 5 3 rd A nn ua l M ee tin g o f N e u rop a th o -log is ts . C h ic a g o , 1 9 77 , p 63 3

2 8 . S c he ib e l M E , L in d say R D . T o m iy asu U , e t a l: P ro g re ss ive de n-d ritic ch an ge s in ag in g h u m a n corte x . E xp N eu ro l 47 :39 2 -40 3 ,J un 19 75

2 9 . U e m u ra E , H a rtm a nn H A : R N A co n te n t an d v o lum e o f n e rve ce llb od ie s in h u m a n bra in . I. P re fron ta l co rtex in a g in g no rm a l an dd e m e n te d p a tien ts . J N e u rop a th o l E xp N e uro l 3 7 :4 8 7 -4 96 , S ep1 9 7 8

3 0 . B on da re f W : E x tra ce llu la r sp a ces in the a g ing ce reb ru m . [In ]T e rry R D , G e rsho n 5 , e ds : N e u rob io lo g y o f A g ing . N e w Y ork ,R a ven P ress , 1 97 6 , pp 16 7-18 1

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32 . H e id a ry H , T om as ch J : N eu ro n nu m b e rs a nd pe rik a ryo n a rea sin th e hu m a n ce re be lla r n uc le i. A c ta A n a t 74 :29 0 -2 9 6 , 19 69

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34 . V ijaya sh an ka r N , B ro dy H : A g in g in th e h u m an b ra in s te m . As tu d y o f th e n u c le u s o f th e tro ch le a r n e rve . A c ta A na t 9 9 :1 69 -1 72 , 1 97 7

35 . W e lls C E : C P w o n ic b ra in d isea se : a n o ve rv iew . A m J P s ych ia try13 5: 1- 12 , J an 1 97 8

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3 7 . P en n R D . B e la n ge r M G , Y as no ff W A : V e n tricu la r vo lu m e in m a nc o mp u te d from C A T sca n s . A n n N e uro l 3 :2 16 -2 33 , M a r1 9 7 8

3 8 . Je rn ig an T L , Z a tz L M , N a ese r M A : S e m iau tom ate d m e tho ds fo rqu an tita ting C S F vo lu m e on cra n ia l co m p u te d to m o g rap h y .R a d io log y 1 3 2 :4 63 -46 6 , A u g 19 7 9

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