Dementia o f the Alzheim er-type and Patients with the Dem entia
Syndrom e of Depression
by
Soraya Lotus Am anullah
B.A., University o f Pennsylvania, 1983 M.S., Drexel University, 1989
«•: ‘ ' A Dissertation Submitted in Partial Fulfillm ent o f the
Requirements for the Degree of DOCTOR OF PHILO SO PHY in the Departm ent o f Psychology
We accept this thesis as conf „>rming to the required standard
Dr. O. Spreen, Supervisor (Departm ent o f Psychology)
Dr. M. Joschko, Departm ental M em ber (D epartm ent o f Psychology
Dr. E. Strauss, Departm ental M em ber (Departm ent o f Psychology)
Dr. B. H a rve yrO iitsid e [\M rnber^Psy^holdgical Foundations of Education)
Dr. H. Tuokko, External Examiner (University o f British Columbia) © SO RAYA LOTUS AM AN ULLAH , 1993
University o f Victoria
All rights reserved. Dissertation may not be reproduced in whole or in part, by photocopying or other means, w ithout the perm ission o f the author. /H ft
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ABSTR AC T
Dementia is characterized by a progressive decline in intellectual, m em ory and other cognitive functions. Alzheimer's disease (DAT) is the most prevalent cause o f dem entia in later life. M emory im pairm ent may be the first sym ptom to herald the onset o f the disease. The dem entia syndrome o f depression (DEP) may also be associated with a m emory im pairment which m ay m asquerade as dem entia in the elderly. Thus both types o f patients may present with m em ory problems; DAT patients m ay also experience concomitant depression, and the distinction between DAT and DEP patients may be a difficult one. T he current criteria fo r the diagnosis o f DAT are generally exclusionary, that is, o th e r possible causes o f the dem entia need to be ruled out before making the diagnosis. Therefore, the identification of a neurobehavioral m arker fo r DAT could increase diagnostic accuracy by reducing the overall error rate. A lterations in neurotransm itter system s have been found in neurologic and psychiatric conditions Decreased cholinergic functioning has been associated w ith DAT while disruption o f the noradrenergic system has been postulated in depression.
Recurrent perseverations, the inappropriate repetition o f a previous stim ulus or response into a current response, have been associated with cholinergic system dysfunction (Fuld, 1982). Continuous perseverations, the inappropriate
repetition o f aspects o f the current response, have been associated w ith
noradrenergic functioning (Sandson & Albert, 1987). Thus, a qualitative scoring o f m em ory tasks for the presence and types o f perseverative errors m ay serve to increase diagnostic accuracy. In particular, w e hypothesized that scoring errors o f com m ission as well as errors of om ission could be used to d a ssify subjects into diagnostic groups. Additionally, we hypothesized that the DAT group w ould make a higher proportion o f recurrent perseverations than the DEP group, w hile
the DEP group would make a higher proportion of continuous perseverations. Data from one verbal and one visual subtest o f the W echsler Memory Scale (WMS, W echsler. 1945) from 49 DAT patients and 39 DEP patients were rescored fo r the presence of both errors of om ission and errors of com mission. These error scores were used in a discrim inant function analysis with 85 percent correct classification overall. Commission errors were also scored fo r the type of error, i.e recurrent or continuous. Proportion scores were derived fo r the
num ber o f each type o f perseverative error to the total num ber of perseverative errors. A m ultivariate analysis of variance on the proportion scores
dem onstrated th a t the DAT group produced a higher proportion of recurrent perseverative errors than did the DEP group. Further, the DEP group produced a higher proportion o f continuous perseverations than did the DAT group.
Results w ere discussed in relation to possible underlying mechanism s. Examiners:
Dr. O. Spreen, Supervisor (Departm ent o f Psychology)
Dr. M. Joschko, Departm ental M em ber (Departm ent o f Psychology
Dr. E. Strauss, Departm ental M em ber (D epartm ent o f Psychology)
Dr. B. Harvey, O utside M ember (Psychological Foundations o f Education)
Table o f C ontents
A ckn ow ledge m en ts... ... D e d ica tio n ... In tro d u ctio n ... Alzheim er's D isease... N e uropathology... N e uro chem istry... Experimental S tu d ie s ... Neuropsychological S tudies... Memory T e stin g... Dementia Syndrome of D e p re s s io n ...
N e uropathology... N e uro chem istry... Lateralization of Neurotransm itter S yste m s... Memory T e s tin g ... Perseverations and In tru s io n s ... Com parisons of Memory Perform ance... Perseverations in Memory P e rfo rm a n ce ... Research Q u e s tio n s ... M e th o d s ... S ubjects... P ro ce d u re s... R e s u lts ... D iscussion... B ib lio g ra p h y ... Appendix A ...
Table 1. Scoring Criteria fo r Omissions on the Visual
Reproduction Subtest of the W echsler Memory Scale (1 9 4 5 )... Appendix B ...
Table 1: Means and (Standard Deviations) fo r Age, Sex Distribution (Sex), and Vocabulary Scaled Scores and Memory Quotients (M Q )... Table 2: Inter-Rater Reliability C orrelations fo r Dependent
Variables and T o ta ls... Table 3: F tests and Significance Levels for Age E ffe cts... Table 4: Means and (Standard Deviations) for Age, Sex
Distribution (Sex) and Vocabulary Scaled Scores of Age Equivalent G roups... Table 5: Mean Logical Memory (LM) and Visual
Reproduction (VR) Scores by G ro u p ...
vi
,vii
.1 2 4 4 .5 7 8 9 .10 .11 12 ,13 .15 .18 ,20 ,24 .26 ,26 .27 ,31 ,36 .44 .53 .53 .54 .54 .55 .56 .56 .57Table for Total S a m p le ... 58
Table 7: Discrim inant Function Analysis Classification Table for Age Equivalent G ro u p s ... 58
Table 8: Mean Proportion Scores fo r G: ■ !ps...58
Table 9: Mean Proportion Scores fo r Age Equivalent G ro u p s... 59
Table 10: Intercorrelation M atrix of Dependent V a ria b le s... 60
A ppendix C ... 61
Figure 1: Example of Continuous P erseveration...61
Acknowledgem ents
1 would like to take this opportunity to express my appreciation to everyone who has helped me in this endeavor.
I am deeply indebted to each of my professors who provided instruction and direction for my work. Very special thanks are extended to Dr. Otfried Spreen fo r his sage guidance and enduring patience. Special thanks are extended to the other members of my committee, Dr. Joschko, Dr. Strauss, Dr. Harvey and Dr. Tuokko, for their very helpful suggestions and comments.
It has been very com forting to have the support of Mr. Stephen Natishin. W ithout the generous gift o f his time and faithful encouragem ent, this work w ould likely remain an idea, rather than a com pleted project. I say this from the heart, I am deeply and forever grateful.
Thanks are also due to the w onderful staff in the Psychology O ffice for all the help I have received. This work was also supported by a grant from the Sara Spencer Foundation. Thanks again to everyone who has assisted me in this undertaking. I have learned much from all of you.
Dedication
This dedication is intended to honour someone who holds a special place in my heart. Although it is difficult to express ir, words, my heartfelt gratitude belongs to my father. He has continually inspired me to strive to achieve my goals and has always provided encouragem ent to do so. I will be eternally gratefui.
Introduction
Dem entia is defined as an acquired progressive im pairm en t in tw o or more areas o f c o g n itive fu n c tio n (Moss & A lbert, 1 9 8 8 ). C um m ings and Benson (1984) re p o rt th a t mild f o m oderate dem entia a ffe c ts betw e en 2 .6 to 1 5 .4 percen t o f the p o p ula tion over th e age o f 65. The d e fin itio n does not im ply a s p e c ific e tio lo g y and indeed, there may be m any causes o f dem entia in c'u d in g A lzheim e r's disease (AD) and depressive disorders (depressive pseudodem entia, Caine, 1 98 1). AD is th o u g h t to a c co u n t for betw een 50 p e rce n t to 7 0 percen t o f all dem entias (Kaszniak, 1 98 6). As such, it a ccou nts fo r the g re a te st p ro p o rtio n o f dem entia in old age. Depression :s estim ated to a ffe c t an estim ated 3 to 7 percen t o f the p o p ula tion over a life tim e (King & Caine, 199 0), and the "in cid e n ce and prevalence (of depression) is highest in th e age group 5 5 -7 0 " (Lipton, 1976, o. 2 9 3 ), It is th e m ajor a ffe c tiv e disorder in the elderly (Schatzberg, Liptzin, Satlin & Cole, 1 9 8 4 ). Folstein and M cH ugh (1978) estim ated th a t
a p p ro xim a te ly h a lf o f depressed elderly patients e x h ib it co g n itiv e im pairm ents sim ilar to patie nts w ith an organic dem entia. S im ilarly,
Reynolds, Perel and Kupfer (1987 ) found th a t in m ore than one th ird (6/1 6) o f th e ir patie nts w ith both sym p to m s o f depression and co g n itiv e
im pairm en t, e ffe c tiv e tre a tm e n t o f the depression resulted in resolu tion of th e c o g n itiv e im pairm en ts as w e ll. Thus, a large p ro p o rtio n o f the elderly p o p ula tion may experience co g n itiv e d iffic u ltie s due to dem entia o f th e Alzheim er ty p e , depression, or both.
A d d itio n a lly , the sym p to m s o f dem entia and depressive
Teri & W agner, 1992). Both groups o f patients may present to r a
n e u ro p sych o lo g ica l evaluation w ith reported m em ory im pairm ents. Also, AD patients may c o n c o m ita n tly experience dep re ssbe sym p to m s (Cum m ings & V ic to ro ff, 1 9 9 0 ; Lopez, Boiler, Becker, M iller, & Reynolds, 199 0), and the s e v e rity o f the depressive s y m p to m a to lo g y may be in verse ly related to the degree o f dem entia (Fischer, Simangi, & Daniolczyk, 1 9 9 0 ). D iffe re n tia tin g dem entia syndrom e o f depression patients from patients w ith dem entia o f the Alzheim er ty p e may pose a d iffic u lt diagno stic challenge. A cco rding to Reynolds and Hoch (1 9 8 7 ) it is "one o f the central clinical and experim ental problem s o f g e ria tric p s y c h ia try " (p .743 ).
T he d iffe re n tia tio n o f patients w ith dem entia o f the A lzi.eim er type fro m p atie nts w ith the dem entia syndrom e o f depression th ro u g n an exa m in a tio n o f errors o f om ission and com ission is the fo cu s o f this
research p ro je ct. T herefore, a brie f re vie w o f the lite ra tu re pertaining to the n e u ro p a th o lo g y and n e u ro ch e m istry associateo w ith A lzh e im e r's disease and depression w ill be hig h lig h te d . A d d itio n a lly, th e co g n itiv e d e ficits associated w ith these disorders w ill also be review ed. H o w eve r, the main em phasis o f th e lite rature review w ill be on the proposed cla ssifica tio n o f perseverative errors and tne p ro d u ctio n c f "hese types o f errors in the p a tie n t groups.
Alzheim er's Disease
A lz h e im e r's disease (AD) is a degenerative disorder characterized by a progressive decline in in te lle ctu a l, m em ory and other co g n itiv e fu nctions. A t present, a diagnosis o f A lzh e im e r's disease is oased on "e lim in a tio n o f all o th e r k n o w n causes o f in te lle ctu a l im p a irm e n t" (Moss & A lb e rt, 198 8, p.
152). T h a t is, a gradual decline in m em ory and o th e r c o g n itiv e fu n ctio n s m ust be docum ented w ith possible causes other than AD ruled o ut. The diagnosis can th e n be designated as 'P robable"; a "D e fin ite " diagnosis requires h isto p a th o lo g ica l co n firm a tio n (M cKhann, Drachm an, Folstein, Katzm an, Price, & Stadlan, 1984).
A major problem w ith the d ia g n o stic process is th a t undetected
causes o f dem entia may s till be classified as A lzh e im e r's disease. F ollow up studies have s h o w n th a t th e incidence o f erroneous diagnosis may be as high as 31 percent (Ron, Toone, Garralda & Lishman, 1 9 7 9 ). "A v a rie ty o f reasons a cco u n t fo r this d iffic u lty , but th e presence o f fu n c tio n a l p sych ia tric illness can be a principal source o f e rro r" (Ron, e t a l., 1 9 7 9 , p. 161).
Indeed, in a three year p ro sp e ctive study o f patients referred to a dem entia clinic, 4 4 o f 225 patients w ere fo u n d n o t to be dem ented. O f these
nondem ented p atie nts, 3 1 , or 70 percent, were diagnosed as depressed (Reding, Haycox, & Blass, 198 5). Since the diagnosis o f AD is prim arily one o f exclusio n, the in tro d u c tio n o f positive signs or sym p to m s m ig h t increase d ia g n o stic accuracy. "S tudies o f D A T could p ro fita b ly c o n ce n tra te on delin eating clinical fu n c tio n s th a t w o u ld a llo w p ositive id e n tific a tio n rather than depending on cu rre n t exclusio nary c rite ria " (Cum m ings & Benson,
198 4, p. 878 ). T h e refore, a noninvasive, neurobehaviorai m arker fo r AD w o u ld be beneficial in reducing errors and increasing d ia g n o stic accuracy (Tierney, Reid, Z o rzitto , S n o w , Fisher, C am pbell-T aylor, & Lew is, 198 6). The aim o f the c u rre n t in v e s tig a tio n is to id e n tify such neu robehaviorai m arkers fo r dem entia o f th e A lzheim e r-typ e (DAT) and th e dem entia syndrom e o f depression (DEP).
Neuropathology
AD is considered a "c o rtic a l" dem entia, w ith the c h a ra cte ristic
presence o f n e u ro fib rilla ry tancles, plaques and granu ovacuolar degeneration (Chui, 198 9). N e u ro fib rilla ry tangles are co n to rte d neurofibrils w h ich
pre fere ntially o c c u r in th e pyram idal cells o f the n eo cortex, the hippocam pus and th e am ygdala (Cum m ings & Benson, 1983), N e u ro fib rilla ry plaques are
"m in u te areas o f tissue d e g e n e 'a tio n consisting o f granular deposits and rem nants o f neurcnal p ro cesse s.... The plaques are co n ce n tra te d in the cerebral co rte x and hippocam pus but also occur in the corpus stria tu m , am ygdala, and th a la m u s" (Cum mings & Benson, 1983, p. 50). The prim ary senso rim o to r c o rte x is generally spared, b u t the "m u ltim o d a l association co rte x is highly prone to neu ro fib rilla ry d e g e n e ra tio n " (Chui, 19 8 9 , p. 808 ). G ranuovacuolar degenerations are clu sters o f in tra c y to p la s m ic vacuoles. The d e g eneration is "h ig h ly seiective fo r the pyram ical neurons o f the h ip p oca m pu s" (Cum m ings & Benson, 1 9 8 3 , p. 5 1 ). A d d itio n a lly , there is neuronal loss and a s tro c y tic hyperplasia w ith in th e co rte x (Cum m ings & Benson, 198 3). The preponderance o f degenerative changes w ith in the hippocam pus m ay be responsible fo r the initial sym p to m o f m em ory disturba nce seen in DAT.
Neurochem istrv
A lth o u g h it is considered a co rtica l dem entia, it has also been show n th a t th e neuronal pop ula tion o f th e nucleus basalis o f M e y n e rt (NbM) is
reduced by " 7 0 p e rce n t" in AD and by "4-7 p e rce n t" in K o rs a k o ff’ s
syndrom e. On th e o th e r hand, there is no marked loss o f these neurons in H u n tin g to n 's disease (HD) (A rendt, Bigl, A rend t, & T en nestedt, 1 9 8 3 ). Thus, th e NbM neuronal pop ula tion is n o t reduced in all dem ented groups.
The NbM is the main source o f choiinergic in p u t to the co rte x.
A ce ty lc h o lin e and choline levels are reduced in AD (Coyle, Price, & DeLong, 1883), "w h e re a s enzym es involved in the synthesis or m etabolism o f other tra n s m itte rs are re la tive ly u n a ffe c te d " (Cum m ings & Benson, p. 53).
P cstsvn a p tic a ce tylch o lin e receptors are not dim inished in AD, suggesting the a lte ra tio n s re fle c t the d y s fu n c tio n o f the ch o lin e rg ic p roje ctions fro m the NbM. The rather selective in vo lve m e n t o f the ch o lin e rg ic system has also been hypo the sized to be a cause o f the co g n itive d e ficits o f AD. "The deg eneration o f th is discrete cholin erg ic neuronal pop ula tion ... is probably d ire ctly related to th e progressive deterio ratio n o f m em ory and o th e r
c o g n itiv e processes in a ffe cte d p a tie n ts " (A rendt et a!., 1 9 8 3 , p. 10 1 ). Due to the p re fe re n tia l in vo lve m e n t o f the cholin erg ic system in AD, some
atte m p ts to find a co g n itiv e m arker fo r AD have been based on co g n itiv e im pairm en ts associated w ith cholin erg ic d y s fu n c tio n in hea lthy c o n tro l subjects. This lite ra tu re w ill be review ed in the fo llo w in g sections.
Experim ental Studies
Drug studies have show n th a t a n tich o lin e rg ic drugs produced m em ory d e ficits in norm al subjects fo r both verbal (Drachm ae, 1 9 7 7 ; D rachm an & Leavitt, 1 9 7 4 ) and nonverbal (M eador, M oore, Loring, Zam rini, & Allen, 1991) m aterial. In an early stu d y, Drachm an and L e a vitt (1974)
d e m o n stra te d a s ig n ific a n t decrem ent in the c o g n itiv e perform an ce o f yot_ng norm als trea ted w ith scopalam ine, a cholin erg ic blockin g agent. S ubjects w e re assessed w ith the W echsler A d u lt Intelligence Scale (W AIS, W echsler, 195 5), a verbal flu e n c y ta sk, and experim ental measures o f m em ory. For the verbal flu e n c y task, subjects w ere asked to lis t orally as many w o rd s as
possible from s p e cific ca te g o ry, such as fru its . One m em ory measure, the supraspan d igit storage te s t, used repeated presen tatio ns o f three
sequences o f 15 digits u n til a p e rfe ct recall was achieved or fo r a m axim um o f five tria ls per sequence. A n o th e r measure, the free recall w ord storage te st, used one o f tw o e q u ivalent 35 w o rd lists fo r th re e learning tria ls ; recall was w ritte n .
S copolam ine alone produced profound im pairm en ts o f storage o f digits and w o rds, despite norm al im m ediate span. M oderate im pairm ent o f se m antic w ord retrieval w a s also observed on the verbal flu e n c y task. In te re stin g ly, the scopalam ine treated subjects "o fte n retrieved item s from a d iffe re n t ca te g o ry afte r a brief tim e " (p .1 16). A d d itio n a lly , Perform ance IQ (PIQ) and Full Scale IQ (FSIQ) w ere s ig n ific a n tly im paired. T re a tm e n t w ith eitf n r m ethscopalam ine (a peripherally acting scopalam ine analog) or p hyso stig m in e (w h ic h a llo w s a cetylch oline to persist at syn a p tic sites) did not produced any s ig n ific a n t changes.
D rachm an (1977) replicated the previous results and fu rth e r delineated a s p e c ific role fo r the ch o lin e rg ic system in m em ory and
in te lle ctu a l fu n c tio n s . Y oung norm als w e re adm inistered scopolam ine; some su bjects w ere also adm inistered p hyso stigm ine, or d-am phetam ine, w h ich in terfere s w ith th e re-uptake o f dopam ine and norepinephrine but does not a ffe c t th e ch o lin e rg ic system . W ith the a d d ition o f p hyso stigm ine, there w ere s ig n ific a n t im p ro ve m e n ts in w ord storage as w e ll as PIQ and FSIQ. The a d d itio n o f a-am phetam ine, h ow ever, produced fu rth e r im pairm ents in w o rd stora ge and a n o n -sig n ifica n t im p ro ve m e n t in PIQ. These findings su g g e st th a t it is sp e c ific a lly the cholin erg ic system w h ich is involved in the p ro d u c tio n o f th e se co g n itiv e and verbal m em ory d e fic its . Scopalam ine has
also beers show n to d isru p t im m ediate and delayed visual m em ory in young norm als on a com ple x fig u re te s t (M eador e t a l.( 199 1).
Neuropsychological Studies
Based on the fin d in g s o f Drachm an and colleagues, Fuld (1 9 8 4 ) re exam ined the data (Drachm an & Lea vitt, 1974) and developed a dem entia profile fo r the W A IS , basco on th e perform ance o f the yo u n g co n tro ls w ho had received scopolam ine. The p a ttern developed was: A > B > C < = D , and A > D, w h ere :
A (Inform ation * Vocabulary)/2 B= (Digit Span + Sim ilarities)/2 C= (Block Design + Digit Syrnbol)/2 D= Object Assem bly
Substituting age corrected scaled scores into the formula, Fuld found that 10 of 19 (53%) drug subjects showed this profile w hile only 4 of 22 controls showed this pattern. In a clinical validation study, Fuld examined the occurrence of the profile in patients with a research diagnosis of AD, m ulti-infarct (MID) or mixed MID-AD dementia. She found that 9 o f 15 testable AD patients (60%) exhibited the profile while only 1 of 15 non-AD patients exhibited the profile.
Brinkm an and Braun (1984) found th a t 13 o f 23 A D -typ e patie nts (57% ) had a positive profile . In co n tra s t, o nly 2 o f 39 M ID subjects had the profile. In both o f these studies, ho w e ve r, the AD group w as older than the MID g ro u p . N evertheless, Satz, Van Gorp, Soper, and M itru sh in a (1987 ) found th a t only 19 o f 149 norm al elderly subjects (1 2 .8 % ) show ed the pattern , and th e re w as no co rre la tio n w ith increasing age.
m arker fo r AD , U n fo rtu n a te ly, altho ugh th e profile has generally been sh o w n to have good s p e c ific ity (fe w false positives), it has lo w s e n s itivity (few tru e positives). In a more recent s tu d y w h ich used more rigorous criteria fo r th e diagnosis o f AD, o niy 13 o f 53 A D -typ e subjects (24% ) had a positive pro file (Goldm an, A xe lro d , G iordanni, Foster, & Berent, in press). W ith co n tin u e d progression o f th e in te lle ctu a l decline, o nly 4 o f the c iig in a l 13 su b je cts w h o in itia lly show ed a positive profile, contin ued to s h o w this profile. Five n e w subjects also show ed th e profile (17% a lto g e th e r on retest). The authors concluded th a t the p rofile w a s not useful fo r accurate id e n tific a tio n o f AD. They state, "perhaps, a m arker based on global in te lle ctu a l fu n c tio n in g does not o ffe r s u ffic ie n t precision in detecting sp e cific ch o lin e rg ic m echanism s and th e ir e ffe cts on c o g n itio n " (p .10).
Memory Testing
The m em ory im pairm ents associated w ith ch o lin e rg ic d y s fu n c tio n may o ffe r m ore precision in the early d e te ctio n o f AD. The earliest phase o f AD has been term ed the "fo rg e tfu ln e s s phase" (Kaszniak, 1986) as m em ory d isturba nce is th e m o st com m on sym p to m to herald the onse t o f the
disease. " D iffic u lty w ith the a cqu isition o f new in fo rm a tio n is generally the firs t and m ost salient sym p to m to em erge in the p a tie n t w ith A D " (Moss & A lb e rt, 19 8 8 , p. 154).
AD patie nts have been sh o w n to have a dim inished im m ediate
m em ory span relative to age m atched co n tro ls fo r both verbal and nonverbal m aterial (Corkin, 1 9 8 2 ). They evidence poorer perform an ce on free recall m easures (Delis, M assm an, B utters, Salm on, Cerm ak & Kramer, 1991) w ith a higher percentage o f responses from th e recency region o f a list than
norm ais (Delis et al., 1 9 9 1 ; Poitrenaud, M oy, Girousse, W olrnark, & Piette, 198 9). Recall and re co g n itio n is also im paired in th e nonverbal dom ain (Moss & M bert, 198 8). AD subjects have also been sh o w n to have higher fo rg e ttin g rates afte r a delay, even if storage ca p a city is equated firs t (D annenbaum , Parkinson, & Inman, 1988). These fin d in g s have led Dannenbaum and colleagues to conclude "p e rfo rm a n ce s o f DAT patients sugg est m u ltiple d e fic its in c'nding re g istra tio n and in storage m aintenance or/and re trie v a l" (Dannenbaum et al., 198 8, p. 230).
Dementia Syndrome o f Depression
W hile m em ory d isturba nce o fte n heralds the on se t o f AD, an im paired a b ility to learn n e w in fo rm a tio n has also been found in depressive patie nts (W eingartner, Cohen, M u rp h y, M artello, & Gerdt, 1 9 8 1 ; Caine, 1 98 6). In elderly depressive patie nts, the associated m em ory im pairm en t m ay m asquerade as dem entia (Post, 1 9 7 5 ). Caine (1981) characterized
pseudodem entia as fo llo w s : (1) an in te lle ctu a l im pairm en t in a p a tie n t w ith a prim ary p s y ch ia tric disord er; (2) th e features o f th e neu ro p sych o lo g ica l ab n o rm a lity resem ble, a t least in part, the presen tatio n o f a
n e u ro p a th o lo g ica lly induced co g n itiv e d e fic it; (3) th e in te lle ctu a l disord er is reversible; and (4) the p a tie n t has no apparent prim ary n e u ro p a th o lo g ica l process leading to the genesis o f th e disturbance. It has been estim ated th a t one th ird (Reynolds, et al., 198 7) to one half (Folstein & M cH ugh,
1978) o f elderly depressed patients e xh ib it severe c o g n itiv e im p a irm e n t due to th e ir a ffe c tiv e state. A lth o u g h Bieliauskas (1993) re ce n tly questioned the c o n c e p t o f pseudodem entia, he state d th a t " if there is a h isto ry o f prim ary d e p re ssio n ..., co g n itiv e sym p to m s m ay indeed have a depressive
c o m p o n e n t" ( p .132). H o w eve r, LaRue, G oodm an, and Spar (1 9 9 2 ) found th a t le n g th o f c u rre n t illness, rather than previous h isto ry was associated w ith s ig n ific a n t m em ory im pairm ents in depressed patie nts, relative to age m atched c o n tro ls . Thus, the variables necessary to produce a dem entia syndrom e o f depression picture have not y e t been fu lly delineated.
N europathology
By d e fin itio n , no k n o w n ne u ro p a th o lo g y is associated w ith depressive pseudodem entia. H o w eve r, the neuroanatom ical su b strate s underlying depression its e lf have been exam ined. In a large s tu d y o f 80 patients w ith le ft sided hem ispheric lesions and 80 patie nts w ith rig h t hem ispheric lesions, a d e p re ssive -ca ta stro p h ic reaction, characterized by te a rfu l o u tb u rsts or a n xie ty reactions, was observed more fre q u e n tly in p atie nts w ith le ft hem isphere than rig h t hem isphere lesions (G ainotti, 1 9 7 2 ). In m ore recent studies, patie nts w ith single hem isphere lesions, verified by com puterized to m o g ra p h y , w e re exam ined fo r the presence o f mood disorders. Patients w ith le ft a n terio r lesions had a s ig n ific a n tly greater fre q u e n cy and severity o f depression. This relatio nship held fo r both co rtica l (Robinson, Kubos, Starr, Rao, & Price, 198 4) and su b co rtica l lesions (S tarkstein, Robinson, & Price, 1 9 8 7 ). On the o th e r hand, right hem isphere lesioned patie nts had a s ig n ific a n tly h igher incidence o f inappropriate cheerfulness (Starkstein, et al., 1 9 8 7 ). In a positro n em ission to m o g ra p h y stu d y o f depressed patients, lo w e r m e ta bolism in the le ft p re fro n ta l region was fo u n d , relative to the right (M a rtin o t, Hardy, Feline, Huret, M azoyer, A tta r-L e v y , Pappata & Syrota, 1 99 0).
A lth o u g h these fin d in g s have n o t alw ays been replicated (Dam,
Pederson, & A hlgren, 198 9), this m ay be due to a num ber o f m eth odological d iffe re n ce s including d iffe re n t sample ch a ra cte ristics, m easures o f
depression, and tim in g o f the assessm ent in te rv ie w . A n o th e r possible c o n fo u n d in g fa c to r is the presence o f a previous p sy c h ia tric h isto ry, as th is m ay in dica te a p redisposition to w a rd s depression, prior to the onset o f the stroke . In a recent stu d y, M orris, Robinson, and Raphael (1992 ) studied 3? patie nts w ith a se m istru ctu re d in te rv ie w and th e M o n tg o m e ry and Asberg Depression Rating Scale. They found th a t th e association o f depression w ith a n te rio r le ft hem isphere lesions held o nly a fte r the in fluence o f a pre e xistin g v u ln e ra b ility to depression w as rem oved. They in te rp re te d these fin d in g s to su gg est th a t lesion lo cation is o nly one o f the fa c to rs involved in p o st-stro ke depression.
N eurochem istrv
S ch iid kra u t (1 9 6 5 ) proposed th e catecholam ine h yp o the sis o f
a ffe c tiv e disorders sta tin g , "som e, if n o t all, depressions are associated w ith an abso lute or relative d e ficie n cy o f catecholam ine s, p a rticu la rly
norepinephrine, at fu n c tio n a lly im p o rta n t receptor sites in the b ra in ".
Depression can be caused by the m onoam ine a n ta g o n ist reserpine (Sachar & Baron, 1 9 7 9 ). F urther su p p o rt fo r the hypothesis com es fro m the observed th e ra p e u tic e ffe c t o f antid epressant m edications. Both m onoam ine oxidase in h ib ito rs and tric y c lic antidepressants are m onoa m inergic agonists. The d isru p tio n o f am inergic in p u t to the hem ispheres m ay result in a "m e ta b o lic e n ce p h a lo p a th y" p ro d u cin g both co g n itiv e and em otion al disorders
D iffe re n t su b typ e s o f depression have been associated w ith d y s fu n c tio n o f eithe r the norepinephrinergic system or the serotonergic system (Maas, 1 9 7 5 ). "T oo little noradrenergic a c tiv ity results in lethargic d epression, and to o little serotonergic a c tiv ity results in agitated depression" (Carlson, 1 9 8 6 , p. 7 0 2 ).
A th ird h yp o th e sis is th a t the ratio o f ace tylch o lin e to the
catech o la m in e s (dopam ine and noradrenaline) is to o high in depressive state s (Liston, J a rv ik & Gerson, 1 98 7). The "re la tive prevalence o f c h o lin e rg ic over am inergic m ediation due to an inverse co rre la tio n o f th e ir a c tiv itie s , plays an essential role in the genesis o f depression in general..., and acquires a special meaning in old age, because fu n c tio n a l im balance o f these tw o system s in the dire ctio n o f a ctiva tio n o f cholin erg ic e ffe c ts is an im p o rta n t fa c to r in aging o f the brain " (Burchinsky, 19 8 5 , p. 10). W hile the e xa ct m echanism s involve d in th e genesis o f depression are not d e fin itiv e ly k n o w n , it appears th a t d isru p tio n o f am inergic fu n c tio n in g
(ca te ch o la m in e rg ic an d /o r indoleam inergic) is a prim ary consideration , w ith p ossibly increased ch o lin erg ic fu n c tio n in g . In c o n tra st, decreased
c h o lin e rg ic fu n c tio n in g is associated w ith A lzheim e r's disease.
Lateralization o f Neurotransrr.itter Systems
It appears th a t d iffe re n t n e u ro tra n sm itte r system s are prim arily in volve d in AD (cholinergic) and depressive pseudodem entia (noradrenergic or s e ro to n e rg ic). T u cke r and W illiam so n (1984 ) review ed evidence to su gg est th a t these n e u ro tra n sm itte r system s co n tro l d iffe re n t aspects o f c o g n itiv e b e h avio ur and are also d iffe re n tia lly lateralized. A c co rd in g to the a uthors, th e ch o lin e rg ic and dopam inergic n e u ro tra n sm itte r system s
re cip ro ca lly regulate co rtica l a ctiv a tio n , w h ile the noradrenergic and se ro to n e rg ic system s re ciproca lly regulate arousal. The
d o p a m in e rg ic/ch o lin e rg ic system is involved in the a ctiva tio n system w h ic h m aintains "to n ic readiness fo r a c tio n " (p. 188). The
n o ra d re n e rg ic/se ro to n e rg ic system is involved in che 'ousai system w h ic h orients to novel in fo rm a tio n a l in p u t. D opam inergic a c tiv a tio n is th o u g h t to increase in fo rm a tio n a l redundancy, w h ile noradrenergic arousal is th o u g h t to prom ote o rie n tin g to n o ve lty.
The authors fu rth e r review ed evidence to sugg est th a t these system s are a s ym m e trica lly lateralized, w ith the ch o lin e rg ic and dopam inergic
system s e x h ib itin g relative ly greater le ft lateralization, and the noradrenergic and s e ro to n e rg ic system s e x h ib itin g re la tive ly greater rig h t la teralizatio n. They su g g e st th a t this d iffe re n tia l lateralization alters in fo rm a tio n -p ro ce ssin g o pe ra tio n s q u a lita tiv e ly . They propose th a t the "re c e p tiv e a tte n tio n a l
c o n tro ls o f a ro u sa l" (p. 202) may be rig h t lateralized, w h ile th e le ft
hem isphere "is linked sp e cifica lly to an active , vig ila n t a tte n tio n a l m ode" (p. 201 ).
D o pam inergic o ve rstim u la tio n results in "h ig h ly routinized m oto r o u tp u t in a nim a ls" (p. 20 4 ). In hum ans, "a t extrem e levels th is may
produce pa th o lo g ica l s te re o ty p y " (p. 2 0 5 ). Noradrenergic depleted animals may be "m o re d istra ctib le by irrele vant cu e s" (p. 191 ). Therefore,
d is ru p tio n to eithe r o f these system s m ay lead to a tte n tio n a l/e x e c u tiv e d e fic its and th e p ro d u ctio n o f perseve ratio ns, to be described below .
Memory Testing
and Gerdt (1981) show ed that depressive patients benefited less from sem antically processing a list of w o rd s to-be-remembered than did controls. Indeed, th e depressives were indistinguishable fro m the controls in
remembering acoustically processed w o rd s. Additionally, w h en these subjects were asked to sort a group of related or unrelated w ords,
depressed subjects later recalled sig nifica ntly fe w e r o f the unrelated words than co ntrols; the groups did not differ in the number of related w o rd s w h ich th e y recalled.
In the third experiment, subjects learned seven d ifferent 32 item word lists. One list used random w o rd s (zero categories); t w o lists had t w o categories w ith the w o rd s either clustered by category or unclustered. T w o lists had fo u r categories w h ic h w e re presented either in a clustered or an unclustered manner. The remaining t w o lists had eight categories w ith presentation in either a clustered or and unclustered order. Depressed patients did not d iffe r fro m controls w h en recalling the lists w ith obvious clustering. H owever, depressed subjects differed sig nifica ntly from controls in the unclustered conditions. The largest differences appeared in the recall o f the random list. The authors com m ented:
"In each study, w e observed that the depressed patients failed to use encoding operations th a t w o u ld be useful in reorganizing in p u t and th a t w o u ld then facilitate later recall. On the other hand, when in form ation w a s presented in an organized or structured fo rm , then th a t organization was appreciated and used by the depressed patient and resulted in more complete, essentially normal learning-recall p e rfo rm a n c e ” (p. 46).
encoding. Further, they postulated that "some disruption in brain state arousal and activation may account for an encoding processing failure that leads to memory learning failures" (p. 46).
Cohen, W ein gartner, Smallberg, Pickar, and M urp hy (1982) tested depressive patients w ith both m o to r and m em ory task',. They found th a t depressives were impaired on a conso n a n t trigram task at delays o f zero to 18 seconds. A d ditio nally, th e y fo u n d th a t there was a sig nifica nt negative correlation betw e en mood and both peak and sustained m oto r performance on a hand d yna m o m eter task. The authors interpreted these findings os "a single d eficit in the area o f the central m otivational state " (p. 596). Thus, the m em ory im pairments associated w ith depression have often been characterized as deficits o f " e ffo rtfu l" versus "a u to m a tic " processing (Grafman, W eingartner, Lawlor, M ellow , Thompsen-Putnam , & Sunderland, 1990).
Depressives have also been found to s h o w im pairments on nonverbal tests o f m emory. Caine (1981) found th a t depressives c o m m o n ly om itted details fro m their draw ings and w e re impaired, relative to age matched controls, on a te s t of immediate visual memory.
Perseverations and Intrusions
Perseveration "is generally used to describe any contin uation or recurrence of experience or a c tiv ity w ith o u t the appropriate stim ulus"
(Sandson & Albert, 1984, p. 715). Prior-itern intrusive errors are defined as "th e inappropriate intrusion o f previously presented stim uli into an
in dividual's cu rre nt perform ance on a cogn itive ta s k " (Troster, Jacobs, Butters Cullum, & Salmon, 1989). Perseverations and intrusions appear to
be ."he same e ntity, i.e., an inappropriate response based on current or past a ctivity. A distinction has sometim es been drawn in w h ic h a perseveration is considered to be a repetition w ith in the same cognitive mode or l!st, and an intrusion is considered to be an inclusion of an extra-list item (Delis, Kramer, Kaplan, & Ober, 198 7). A t least t w o theoretical models have been proposed to explain perseverative behaviour.
Goldberg and T ucke r (1979) proposed a ta x o n o m y o f perseveration w h ic h delineated four d ifferent types o f perseveration. These are:
perseveration o f activities, perseveration of features, perseveration of elements, and hyperkinesia-like m otor perseveration. Sandson and Albert
(1987) proposed a similar ta x o n o m y o f three d ifferent ty p e s of perseveration. These are: stuck-in-set perseveration, recurrent
perseveration and continuous perseveration. A lth ough Goldberg and Tucker developed the ta x o n o m y from an empirical study, and Sandson and Albert developed their classification based on a literature review, the t w o
ta xo n o m ie s are quite similar.
Perseveration o f activities and stuck-in-set perseveration both refer to the contin ued inappropriate maintenance of a previous set or fra m e w o rk so th a t sem antic categories or types of a c tiv ity are confused. Examples are: the inability to s w itc h from w ritin g w o rd s to performing m athematical c o m p u ta tio n s (Goldberg & Tucker, 1979) or, in contin uin g to bisect lines w h en th e n e w task is to c o n n e ct circled numbers sequentially, (after previously bisecting linesMSandson & Albert, 1984).
Hyperkinesia-like perseveration and continuous perseveration both refer to th e continued inappropriate repetition of a current behaviour. Examples are: multiple circular d raw ings when asked to d ra w a single circle
(Goldberg & Tucker, 1 97 9) or additional loops instead o f the requested three loops (Sandson & Albert, 1987). An example o f this type o f perseveration is reproduced in Figure 1 o f Ap p e n d ix C. In this example, 16, rather than four, d ots are produced in each quadrant o f the square o f Design B.
Recurrent perseveration is defined by Sandson and A lb e rt (1984) as "the u nintention al repetition, after cessation, o f a previously emitted response to a subse quen t stim ulus" (p. 7 2 7 -7 2 8 ). Goldberg and Tucker further subdivide recurrent perseveration into t w o types: perseveration o f features and perseveration of elements. Perseveration o f elements is the repetition of an ontire previous response. For example, the repetition o f a circle w h e n asked to d ra w a cross after just drawing a circle (Golaberg & Tucker, 1979), or repeating "lay o n " as a definition fo r ship after having defined bed as "lay on" previously, or repeating the number " 7 " when asked to d ra w a clock (Sandson & Albert, 1984, p. 731). Perseveration of
features involves confusion o f the "generic aspects o f the shapes" (p. 280). For example, dra w in g a cross as t w o intersecting lines out then draw ing it as a Greek cross after dra w in g a circle. An example o f recurrent visual perseverations is provided in Figure 2 of A ppendix C. In this example, the " X " fro m Design A is inappropriately repeated in Design B, rather than the corre ct prod u ctio n of a square figure. Thus, perseverations can be elicited in a va rie ty of w a y s w ith both verbal and nonverbal tasks.
Goldberg and Tu cke r (1979) considered perseveration to reflect a b re a kd o w n of diffe re n t levels o f cogn itive processing (executive, motor, or sem antic). Sandson and Alb e rt (1987 ) proposed th a t perseverations were based on disruption o f d iffe re n t anatom ic and neurochemical systems. A cc o rd in g to th e ir model, recurrent perseverations may be related to
decreased brain levels o f acetylcholine and left hemisphere function. Continuous perseverations may be associated w ith noradrenergic system d y s fu n c tio n and right hemisphere fun ctio n . Stuck-in-set perseverations may be related to dopam inergic system and frontal system functio n in g .
While perseverations can be elicited in a variety of d ifferent tasks, the m em ory im pairm ent exhibited by the AD ty p e and depressive
pseudodementia patients is o fte n the presenting feature o f the disorders. Since th e n e u ro transm itte r systems prim arily involved in A D and depressive pseudodementia appear to be different, and these systems are possibly related to the observed m emory impairments, the most fru itfu l search fo r a behavioral marker for AD may begin by examining m em ory performance in AD patients fo r the presence o f perseverative errors in co n tra st to the performance o f depressive pseudodementia patients. Alth o u g h both the AD type and the depressive pseudodementia type groups display m emory
impairments, there may be a d iffe re n t pattern associated w ith each group's performance.
Comparisons o f Memory Performance
Gainotti, Caltagirone, Masullo, and Miceli (1980) w e re unable to distinguish depressed fro m demented patients using global measures of verbal and visual m emory. Indeed, according to Cumm ings and Benson (1983), "m e m o ry disturbance cannot be used to distinguish degenerative dementias fro m the dementia syndrom e o f depression" (p. 241).
Dannenbaum, Parkinson, and Inman (1988) studied a group of normal controls, depressed, and demented subjects (Alzheimer-type) w ith a Brown- Peterson paradigm, administered via com puter. Letter spans were
significantly d iffe re n t am ong the three groups w ith controls perform ing better th a n depressives and depressives perform ing better than demented subjects. When a subgroup of depressed and demented patients were matched fo r le tter span, the A D -type subjects perform ance was significantly lower th a n the depressives only on delayed free and serial recall, and not on immediate recall. H owever, a limitation o f this stu d y is th a t the AD patients were s ig n ific a n tly older than the depressive subjects. Also, the depressed subjects were recruited fo r the s tu d y and were not referred fo r the
evaluation of m em o ry im pairments.
W hitehe ad (1973) evaluated depressed and demented patients at a psychiatric hospital. Depressed subjects were also retested w h en th e y were th o u g h t to be clinically remitted. Subjects did not diffe r on mean
Vo cabulary age corrected scaled sores o f the W AIS. On a number o f verbal learning tasks th e demented subjects performed w o rse than the depressed subjects. The dem ented patients made more false positive and random errors as well as more omission errors than the depressives. H owever, the depressives w e re more prone to omission errors w h ile ill than w h en in a remitted state. A major limitation w ith this study, how ever, is th a t half the demented subjects were also clinically depressed. This w o u ld serve to obscure some differences between the groups.
Poitrenaud and co w o rke rs (1989) tested mildly and m oderately impaired dem ented and depressed subjects. The depressives and mildly demented subjects exhibited similar recall rates o f a ten w o rd list over three trials. Tne num be r of subjects w ith three or more omissions did not
separate the groups. H owever, the number o f false alarms on recognition testing did separate the groups, w ith the mildly demented group displaying
more false alarms than the depressed group. A problem w ith this study is th a t the depressed subjects w e re selected by medical exam, but they were n o t referred for evaluation o f m emory problems.
Perseverations in Memory Performance
A lth o u g h the same overall score may be achieved by varying means by d iffe re n t diagnostic groups, the use o f a qualitative approach, such as error analysis, may prove useful in differentiatin g groups. For example, Brandt, Folstein, and Folstein (1988) used an analysis o f error patterns to dem o n stra te distin ct cognitive profiles in groups o f AD and H u n tin g to n 's disease patients w h e n they vere matched for total score on the Mini-Mental State Exam. AD patients w e re s h o w n to make more errors on the
orien ta tion and recall sections than HD patients, and the HD patients were s h o w n to make more errors than AD patients on the serial sevens task. These distinctions were independent o f the severity level of the dementia. Heindel, Salmon, and Butters (1989), in a re vie w of th e literature,
highlighted studies w h ic h used analyses of error patterns to differentiate dem ented patient groups fro m each another. Cumm ings and Benson (1984) state e xplicitly, "n e u ro p sych o lo g ic studies should conce ntrate on
determ ining the qualitative differences between d iffe re n t dementing d isorders" (p. 877).
W h e n AD patients have been asked to make draw ings from semantic m em ory, perseverations have been observed. Brantjes and Bouma (1991) qua lita tive ly examined the draw ings o f moderately to severely demented AD patients w h o were asked to d ra w 12 items fro m m em ory in a specified order. The draw ings, a table, w a tc h , bird, etcetera, w e re then examined for
the num ber o f omissions, sim plifications, confabulations and perseverations. The d ra w in g s were also analyzed fo r spatial disorientations, stereotypies
(the addition o f more details than necessary), and type o f perseveration. Relative to age matched controls, the AD subjects made more errors o f omission, sim plification, c onfabu latio n and perseveration. Perseverations of activities, perseverations o f features, and hyperkinesia-like perseverations were o n ly observed in the draw ings o f the AD patients. In contrast, the control subjects made more stere otyp ic errors than did the AD subjects.
Increased numbers o f recurrent perseverative errors, or intrusive errors, have been found in the performance o f AD patients on both verbal (Delis, M assman, Butters, & Salmon, 1991; Fuld, 1983) and nonverbal m em o ry tasks (Jacobs, Salmon, Troster & Butters, 1 9 9 0 ; Jacobs, Brandt, Salmon, Heindel, Troster & Butters, 1991; Troster, Jacobs, Butters, Cullum, & Salmon, 198 9). Fuld (1983) found th a t Alzheimer patients made a higher num ber o f intrusive errors on a modified Blessed mental status exam and the Fuld-Object M em ory Evaluation than normal control subjects. Delis and colleagues (1991 ) also found th a t A D patients made more intrusive errors than sim ilarly demented Fluntington's disease patients on the California Verbal Learning Test. Additionally, using recall o f figural material from the Visual Reproduction subtest o f the W echsler M em o ry Scale (WMS), Jacobs, Salmon, Troster, and Butters, (1990) and Troster and colleagues (1989) found A lzheim e r patients made more prior-item intrusive errors than did H u n tin g to n ’s patients or normal controls. Intrusive errors have also been found in the profiles o f only mildly dem ented AD patients (Jacobs, et al., 1991).
correlated w ith choline acetyltransferase levels (Fuld, Katzman, Davies, & Terry, 198 2). Ho w eve r, plaque counts were also significantly higher in patients w ith intrusions than in those w ith o u t (Fuld, 1983). Thus, increased numbers o f intrusions in AD patients have been correlated w ith both
decreased choline acetyltransferase levels and increased plaque counts. From these results it is not possible to determine if decreased choline acetyltransferase alone is su fficie n t to produce intrusions.
AD patients tend to produce high numbers o f intrusive errors on both verbal and nonverbal m emory tests. Thus, the te n d e n cy to produce
intrusive errors appears to be a rather ubiquitous finding in Alzheimer patients.
On the other hand, depressive patients appear to make more errors of omission than o f com mission (Cummings & Benson, 1983). W eingartner and colleagues, (1981 ) found th a t depressive patients did not make more intrusive errors than normal control subjects on a variety o f verbal memory tasks. L ow enstein et al. (1991) studied a group o f probable AD subjects,
patients w ith multiple cerebral infarctions (MCI), depressed inpatients and outp a tie n ts, and normal controls using the Fuld Object M em ory Evaluation. Intrusive errors w e re categorized as either sh ift intrusions, te st intrusions, c once ptu al intrusions, co n fa b u la to ry intrusions, or unrelated intrusions. The mild AD subjects evidenced more unrelated intrusive errors than the mild MCI patients, the depressed patients, or the normal controls. The groups did not d iffe r in the occurrence o f other types of intrusive errors. However, 17 o f th e 31 depressed patients were not referred for evaluation of m emory com pla ints but w e re recruited for the study. Both groups of depressed subjects w e re included to g e th e r fo r the purposes o f the statistical analyses.
Therefore, more than half o f the depressed subjects w o uld not pose a diagnostic problem fo r the differentiation o f dementia versus depression. Nevertheless, these findings to g e th e r w o u ld suggest th a t a qualitative approach, utilizing error analysis, o f m em ory test perform ance m ig h t be useful in differentiating AD from elderly depressive patients.
In sum, errors o f com m ission reliably have been found to d ifferentiate groups o f control subjects and patients w ith AD and H u n tin g to n 's disease. On the other hand, depressive patients have not been s h o w n to make these types o f errors, rather th e y have been s h o w n to make errors o f omission. These findings suggest th a t these patients perform poorly on m em ory tests fo r d iffe re n t reasons.
Research Questions
The purpose of th e present study was to address t w o general questions. I. Is the presence of intrusive or recurrent perseverative errors in m em o ry test perform an ce specific to Alzheimer type demented patients such t h a t their presence or absence can provide a useful discrimination betw e en these patients and elderly depressive patients? II. Do the different types o f perseverative errors found supp ort the distinctions proposed by Sandson and A lb e rt (1987 )? The purpose was not to compare the overall level o f perform ance on neuropsychological tests between the groups. To address Question I, w e tested the hypothesis th a t patients w ith AD-type dementia and elderly depressive patients fail m em ory tests for different reasons. More specifically, it was hypothesized th a t the D A T patients would make more intrusive or recurrent perseverations than DEP patients. A d ditio nally, it w a s hypothesized th a t DEP patients would make more omissions and c o n tin u o u s perseverations than DA T patients, using the W echsler M e m o ry Scale. Further, it was hypothesized th a t the error scores w o uld be reliable enough to predict group m embership (above chance levels). An accepted w a y to te s t these hypotheses is to use discriminant fu n c tio n analysis (Adams, 1979), w h ic h can be useful in "fin d in g the underlying mechanisms o f group differences" (p. 260).
To address Q uestion II, w e analyzed the typ e s of errors made. It was hypothesized th a t the ty p e s of com mission errors made w o u ld differ by group, w ith the DA T patients producing a higher proportion of intrusive errors or recurrent perseverations than the DEP group, and w ith the DEP patients producing a higher proportion o f contin uous or hyperkinesia-like perseverations th a n the D A T group. This hypothesis was tested using a
Methods
Subjects
Subjects w e re selected from a sample o f patients seen for a
neuropsychological evaluation at a rehabilitation hospital. All patients had been referred by a neurologist for the evaluation. The files were housed at the U n ive rsity o f Victoria N e uro psychology Center. The sample was drawn from th e files available fo r patients evaluated fro m 1983 to the present. Archival data were used to increase the potential sample size. All patients previously gave conse nt fo r their test data to be used for teaching or research purposes, provided th a t the patient remained ano nym ous and identifying in form ation was not used.
A fte r com ple tion o f the neuropsychological evaluation and any additional diagno stic tests, subjects w e re classified into one o f t w o
categories by the referring neurologist or the neu ro psychologist. Subjects in Category One w e re classified as brain damaged (Category 1), those in
Category Five w e re classified as p s y c h o tic /n e u ro tic (Category 5). All files of patients over the age o f 55 years from Categories 1 and 5 w h o were
referred fo r evaluation o f either dementia or m em ory com plaints were examined. Subjects were excluded if th e y had focal neurological signs on recent neurological exam ination or if there was a significant history o f head trauma, neoplastic or vascular disease, or alcohol or drug abuse. Patients
w ith a previous or current psychiatric history w e re also excluded from the DAT group. Alzheim er-type patients w e re considered possibly "dem en ted " by the n e u ro p s y c h o lo g is t and/or the referring physician and met NINCDS- ADRDA d iagno stic criteria fo r possible AD (McKhann et al., 1984). All remaining AD patients w h o were assessed w ith the W echsler M em o ry Scale
(WMS, Wechsler, 1945) were included in the study.
Dementia syndrome o f depression patients were also referred by a neurologist for evaluation of m em ory problems or possible dementia. Subjects were excluded from th e depressed group according to the same criteria as the AD type group w ith the exception o f a positive psychiatric history. The depressed subjects were included if they w e re considered "depressed" by the neuropsychologist, based on th e ir presenting sy m p to m s and some test results from tests such as: the Minnesota M ultiphasic
Personality Inventory (MMPI), the Geriatric Depression Scale, the Zung Depression Scale, or the Beck Depression Inventory. It was not always possible to determine if the patient w o u ld meet diagnostic criteria fo r major depression, based on DSM-III-R criteria. Five o f the DEP subjects were previously treated w ith electroco nvulsive shock th erapy (ECT). Four DEP subjects were being treated w ith antidepressants at the tim e o f testing. One sub je ct was considered to have a bipolar diagnosis, how e ve r, the subject was depressed at the tim e o f testing. A n y ambiguous cases for either group w e re referred to a board certified neu ro psychologist (Dr. Otfried Spreen) w h o made th e final decision to include or exclude the patie nt fro m the sample.
Procedures
T he W echsler M em ory Scale (Wechsler, 1 94 5) te s t scoring fo rm s and draw ings were photocopied w ith the p a tie n t's name om itted fro m the copy. Only the file num ber remained on the co p y fo r id entificatio n purposes. Other data was obtained from the patient file data base available at the University o f Victoria.
All tests were administered according to standard instructions (Spreen & Strauss, 1 99 1), by a trained psychometrician or advanced clinical
neu ro p sych o lo g y students. The same psychom etrician supervised the
s tu d e n t adm inistration. The Vocabulary subtest o f the W echsler Adult
Intelligence Scale - Revised (WAIS-R, Wechsler, 1981) was examined and
scores used as an estim ate of premorbid fu n ctio n in g . A lthough other
measures such as educational level or rankings o f current or previous occu p a tio n could be used to estim ate premorbid functio n in g , the Vocabulary su b te st was chosen as this data was more reliably available fro m the data
base. T w o subtests fro m the W echsler M em ory Scale (WMS, Wechsler,
1945) were also examined for both groups: the Logical M em o ry (lM)
s u btest and the Visual Reproduction (VR) subtest. The original Wechsler
M e m o ry Scale was used as previous research has s h o w n that more intrusive errors are elicited w ith its use than w ith the revised version (Troster et al., 198 9).
The LM su btest consists o f t w o brief narrative stories w h ic h are read aloud to the subject. A fte r com ple tion o f the stories, the subject is asked to repeat as much o f the story as he/she can remember. Recall is recorded verbatim by the examiner. The VR stimuli consist o f three cards w ith one design on each o f the first t w o cards and t w o designs on the third card. The subject is presented w ith each card fo r 10 seconds. The card is w ith d ra w n fro m v ie w and the subject asked to reproduce the designs from m em ory. Generally, the subject was given a separate 8.5 X 11 inch sheet o f paper for each draw ing.
Omissions fo r LM were scored according to the gist scoring criteria of Spreen and Strauss (1991 ). These criteria are more lenient than the original
