3rournal ofNeurology, Neurosurgery, and Psychiatry 1996;61:381-387

Neuropsychological and psychiatric differencesbetween Alzheimer's disease and Parkinson'sdisease with dementia

Sergio E Starkstein, Liliana Sabe, Gustavo Petracca, Eran Chemerinski, Gabriela Kuzis,Marcelo Merello, Ramon Leiguarda

AbstractObjective-To examine neuropsychologi-cal and neuropsychiatric differencesbetween patients with probableAlzheimer's disease and patients withParkinson's disease and dementia.Methods-Thirty three patients withprobable Alzheimer's disease and 33patients with Parkinson's disease anddementia were matched for age, sex, andmini mental state examination scores andgiven a battery of neuropsychological andneuropsychiatric tests.Results-Patients with Parkinson's dis-ease with dementia had a significantlyhigher prevalence of major depressionthan patients with Alzheimer's disease;patients with Alzheimer's disease showedmore severe anosognosia and disinhibi-tion than patients with Parkinson's dis-ease. Whereas no significant betweengroup differences were found on tests ofmemory and language, demented patientswith Parkinson's disease had a signifi-cantly greater impairment on a test ofvisual reasoning than patients withAlzheimer's disease.Conclusion-There were significant psy-chiatric differences between patients withAlzheimer's disease and dementedpatients with Parkinson's disease, butneuropsychological differences wererestricted to a single cognitive domain.

(3 NeurolNeurosurg Psychiatry 1996;61:381-387)

Department ofBehavioral NeurologyS E StarksteinL SabeG PetraccaE ChemerinskiG KuzisDepartment of ClinicalNeurology, RaulCarrea Institute ofNeurological Research,Buenos Aires,ArgentinaS E StarksteinM MerelloR LeiguardaCorrespondence to:Dr Sergio E Starkstein, RaWi1Carrea Institute ofNeurological Research,Montafieses 2325, 1428Buenos Aires, Argentina.Received 18 March 1996and in revised form28 May 1996

Accepted 6 June 1996

Keywords: dementia; Alzheimer's disease; Parkinson'sdisease

Alzheimer's disease and dementia inParkinson's disease have been considered themost frequent types of cortical and subcorticaldementia respectively. Cummings andBenson' suggested that there should be differ-ences in cognitive, emotional, and motorimpairments in cortical and subcorticaldementias. In cortical dementias cognitivedeficits are characterised by impairments inlanguage and memory, agnosia, and apraxia.In subcortical dementias, cognitive deficits arecharacterised by a general slowness of thoughtprocesses, and impaired manipulation ofacquired knowledge (for example, deficits inabstracting abilities, retrieval, and visuospatialfunctions). Cummings and Benson furthersuggested that lack of concern (anosognosia)and disinhibition may be more frequent in cor-

tical dementias, whereas apathy or depressionmay be more prevalent in subcortical demen-tias.' Finally, they also pointed out thatalthough motor abnormalities may be absentin cortical dementias, disorders of movement,tone, posture, and gait are universal in subcor-tical dementias.None the less, the classification of the

dementias into cortical and subcortical types isa controversial issue. Several authors sug-gested that this classification scheme should beabandoned,23 because at necropsy, brains ofpatients with cortical dementias also featuresubcortical pathological change (for example,depletion of cholinergic neurons in thenucleus basalis of Meynert in Alzheimer's dis-ease), and similarly, brains of patients withsubcortical dementias may also show corticaldamage (for example, cortical atrophy inHuntington's disease).' Another confoundingissue is that cortical and subcortical dementiasmay coexist in the same patient. For example,several studies reported patients withParkinson's disease and dementia who alsoshowed the characteristic neuropathologicalfeatures of Alzheimer's disease.4

Neuropsychological differences betweenpatients with Alzheimer's disease anddemented patients with Parkinson's diseasehave been examined in several studies.Whereas Mayeux et al could not find signifi-cant differences between patients withAlzheimer's disease and demented patientswith Parkinson's disease on a test of globalcognitive functions,5 studies using moredetailed neuropsychological assessmentsshowed significant between group differences.67Affective changes have also been reported inboth Alzheimer's disease and Parkinson's dis-ease. Most studies showed either dysthymia ormajor depression in about one third of patientswith Parkinson's disease,8 and a similar preva-lence of depression has been reported inAlzheimer's disease.9 However, the prevalenceof depression among patients with Parkinson'sdisease and dementia has not been examined,and to our knowledge, whether affective disor-ders have a different prevalence in Alzheimer'sdisease and patients with Parkinson's diseaseand dementia has not been assessed.Moreover, whereas Cummings and Benson'speculated that patients with Alzheimer's dis-ease may be more anosognosic than dementedpatients with Parkinson's disease, this hypothe-sis has not been empirically examined.Motor disorders such as tremor, rigidity,

and akinesia are the hallmark of Parkinson'sdisease, but they are also present in about a

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quarter of patients with Alzheimer's disease.'0In a recent study, we showed significant cogni-tive and psychiatric differences betweenpatients with Alzheimer's disease with or with-out extrapyramidal motor signs." Thus tocompare cognitive and psychiatric functioningin patients with Alzheimer's disease andpatients with Parkinson's disease and demen-tia it is important to screen patients withAlzheimer's disease for the presence ofextrapyramidal signs.

Finally, to our knowledge studies using thesame comprehensive neuropsychological, neu-ropsychiatric, and neurological assessments incohorts of Alzheimer's disease and dementedpatients with Parkinson's disease have notbeen carried out. This was the aim of the pre-sent study. Patients with Alzheimer's diseaseand patients with Parkinson's disease anddementia were matched for age, sex, andglobal cognitive performance. None of thepatients with Alzheimer's disease had restingtremor, cogwheel rigidity, or bradykinesia.These groups were compared for cognitiveperformance and psychiatric symptoms.

Patients and methodsPATIENTSA consecutive series of patients with eitherprobable Alzheimer's disease or Parkinson'sdisease who attended the neurology clinic ofthe Raul Carrea Institute of NeurologicalResearch were screened for participation in thestudy.

Alzheimer's disease groupPatients with Alzheimer's disease wereselected from a group of 204 consecutivepatients followed up in the neurology clinic ofour Institute. Patients included in this groupmet the NINCDS-ADRDA criteria for proba-ble Alzheimer's disease." All patients wereexamined with the unified Parkinson's diseaserating scale,'2 and only patients rating 0 onitems of rigidity, tremor, and bradykinesiawere included.

Group with dementia and Parkinson's diseaseThis group comprised 33 consecutive patientsmeeting both the United Kingdom Parkinson'sDisease Society brain bank clinical criteria forParkinson's disease"3 and the DSM-IV criteriaof dementia due to Parkinson's disease'4 whowere examined between January 1993 andDecember 1994. All patients had typical clinicalfeatures of Parkinson's disease and respondedto levodopa. Patients with a history of cognitivedecline before or less than one year after theonset of Parkinson's disease were excluded.Thirty three out of a consecutive series of 111patients with Parkinson's disease wereincluded in the study. All the dementedpatients with Parkinson's disease were assessedwhile in the "on" state.

Each of the 33 demented patients withParkinson's disease were matched for age (±2years), sex, and mini mental state examinationscore (± 1 point) with one patient with probableAlzheimer's disease.

NEUROLOGICAL EXAMINATIONAfter informed consent, patients were assessedby a neurologist with the Unified Parkinson'sdisease rating scale (UPDRS),12 a widely usedscale for assessing the severity of clinical symp-toms in patients with Parkinson's disease. Thisscale has three sections: activities of daily liv-ing, motor examination, and complications ofantiparkinsonian treatment. Item scores rangefrom 0 to 4, and higher scores indicate moresevere impairments.

PSYCHIATRIC EXAMINATIONThe psychiatric evaluation was completed by apsychiatrist blind to the UPDRS scores andneuropsychological findings, and included thefollowing assessments:

Structured clinical interview for DSM-III-R(SCID) '5The SCID is a semistructured diagnosticinterview assessing signs and symptoms neces-sary for the major axis I DSM-III-R diagnoses.The interview was carried out with the patientand at least one first degree relative. Based onthe SCID responses, DSM-III-R diagnoses ofmajor depression and dysthymia were made.

Hamilton depression scale (HAM-D) 16The HAM-D is a 17 item interviewer ratedscale for rating the severity of symptoms ofdepression.

Anosognosia questionnaire-dementia (AQ-D) 17

This instrument consists of 30 questionsdivided into two sections. The first sectionassesses intellectual functioning (for example,Do you have problems remembering dates?Do you have problems remembering tele-phone calls?), and the second section exam-ines changes in interests and personality (forexample, Do you get easily irritated? Have youlost interest in things?). Each answer is ratedas never (0 points), sometimes (1 point), usu-ally (2 points), and always present (3 points).Thus higher scores indicate more severeimpairments. Form A is answered by thepatient alone, and form B (a similar question-naire written in the third person) is answeredby the patient's care giver blind to the patient'sanswers in form A. The final score is the dif-ference between total scores obtained by sub-stracting form B from form A. Thus positivescores indicate that the care giver rated thepatient as more impaired than the patient'sown evaluation (the patient was less aware ofhis or her cognitive and emotional deficits).We have recently showed the reliability andvalidity of this scale.

Bech mania scale'8This scale assesses the presence and severity ofmanic symptoms, such as euphoria, hyperac-tivity, flight of ideas, irritability, hypersexual-ity, and grandiose delusions.

Pathological laughing and crying scale(PLACS) 19

This instrument is an interviewer rated scalethat quantifies aspects of pathological affect,

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including the duration of the episodes, theirrelation to external events, degree of voluntarycontrol, inappropriateness in relation to emo-tions, and degree of resultant distress. Thereliability and validity of this scale in patientswith Alzheimer's disease have been previouslyestablished. The scale is administered to thepatient and at least one first degree relative orcare giver in close contact with the patient.The scale consists of 16 items (eight assessingpathological laughter (PLACS-L) and eightassessing pathological crying (PLACS-C)),which are scored from 0 to 3 points.

Apathy scale20The apathy scale includes 14 items which arescored by the patient's relative or care giver.Each question has four possible answers,which are scored from 0 to 3. Thus the apathyscale score ranges from 0 to 42 points, andhigher scores indicate more severe apathy. Wehave verified the reliability and validity of theapathy scale in Alzheimer's disease.

Irritability scale21This is a 14 item scale which is rated by thepatient's relative or a care giver. Scores rangefrom 0 to 42, and higher scores indicate moresevere irritability. We have verified the validityand reliability of this scale in Alzheimer's dis-ease.2'

Dementia psychosis scale22This 18 item scale quantifies the severity andtypes of delusions in demented patients at thetime of the psychiatric evaluation. It is com-pleted by a psychiatrist during an interviewwith the patient and at least one close relativeor care giver. We have shown this scale to bevalid and reliable in Alzheimer's disease.22

Functional independence measure23This instrument assesses self care, sphinctercontrol, mobility, locomotion, communica-tion, and social cognition on a low level scale.Higher scores indicate less impairments inactivities of daily living.

Social ties checklist24This is a 10 item scale which assesses thequantity and quality of social supports. Scoresrange from 0 to 10, and higher scores indicatebetter social supports.

NEUROPSYCHOLOGICAL EXAMINATIONEach patient was assessed by a neuropsycholo-gist blind to neurological and psychiatric find-ings with the following test battery:

Mini mental state exam (MMSE)25MMSE is an 11 item examination that hasbeen found to be reliable and valid in assessinggeneral cognitive functions and serves as acognitve screemng mstrument in patients withdementia.

Buschke selective reminding test26This test measures verbal learning and mem-ory during a multiple trial list learning task.The patient listens to a list of words and

recalls as many words as possible. Each subse-quent learning trial involves the presentationof only those words that were not recalled onthe immediately preceding trial. The outcomemeasure was the number of words in longterm storage.

Benton visual retention test27This test assesses visual perception and non-verbal memory. Patients are exposed to geo-metric designs for 10 seconds, and areimmediately presented with a card containingthe correct design among three foils. Thepatient is asked to select the previously pre-sented design. There are 10 trials.

Digit span28This subtest of the Wechsler memory scaleexamines auditory attention, and includes twoparts. Both consist of seven pairs of numbersequences that the examiner presents at therate of one per second. In the first part (digitsforward), the patient is asked to simply repeat astring of numbers (from two to eight numbersin length) exactly as it is given. In the secondpart (digits backwards) the patient is asked torepeat the string of numbers (from two toeight numbers in length) in reversed order.

Wisconsin card sorting test (WCST)'9This test measures the ability to develop andapply new concepts, and, subsequently shiftsets, which requires the subjects to suppress alearned response that was previously correctand learn a new one. Assessment of the overallproficiency of the test was judged by the num-ber of categories achieved (maximum 6).

Controlled oral word association test30This test examines access to semantic infor-mation with time constraint. Patients wereinstructed to name as many words beginningwith the letter F as they could in one minute.People's names and proper nouns were notpermitted. The letters A and S were then pre-sented successively, one minute being allowedfor each letter. The score was the combinednumber of appropriate words produced inthree minutes.

Raven's progressive matrices3"This test measures visuospatial reasoning.Patients are presented with a spatial patternproblem with one part removed and four pic-tured inserts, one of which contains the cor-rect pattern. The patient has to select thecorrect piece to match the original spatial pat-terns. The patterns become increasingly com-plex over trials. The performance score is thenumber correctly identified.

Purdue pegboard test32This test assesses manipulative dexterity. Theapparatus consists of a board containing twoparallel rows of 25 holes each and 50 metalpegs. Patients are asked to take the pegs withthe preferred (for example, right) hand andplace them as quickly as possible in the rightcolumn of holes during a 30 second period.The same procedure is repeated with the non-

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Table 1 Demographic and neurologicalfindings

PD dementia group AD group

No of patients 33 33Age (mean y) 71-0 (8-5) 70 3 (8-2)Sex (% women) 30 30Education (mean y) 9-6 (5 9) 10-5 (5 7)UPDRS motor score (mean scores)*** 22-9 (9 8) 0-6 (1 1)

Values in parentheses are SD. PD = Parkinson's disease; AD = Alzheimer's disease.***p < 0-0001.

preferred hand, and the score is the number ofpins inserted in the time for each hand.

STATISTICAL ANALYSISGroups were compared by multivariate analysisof covariance (MANCOVA), and post hoc t

tests, when appropriate. Frequency distribu-tions of dichotomous variables were examinedwith contingency tables, and X2 tests were cal-culated with a Yates' correction for cell sizes<5. For all analyses, tests were two tailed.

ResultsDEMOGRAPHIC AND NEUROLOGICAL FINDINGS(TABLE 1)The Alzheimer's disease and the dementedParkinson's disease groups were matched forage and sex, and there were no significantbetween group differences in education. Onepatient with Parkinson's disease (3%) was inHoehn and Yahr stage 1, 10 patients (31%)were in stage 2, 16 patients (48%) in stage 3,five patients (15%) in stage 4, and one (3%) instage 5. The mean (SD) daily levodopa dosagefor the Parkinson's disease-dementia groupwas 519 (410) (range: 0-1250) mg/day, andnone of the patients were on anticholinergicdrugs.

PSYCHIATRIC FINDINGS (TABLE 2)Demented patients with Parkinson's diseaseshowed significantly higher HAM-D scores

Table 2 Psychiatric findingsPD dementia group AD group

Hamilton depression scale* 12 6 (8 8) 7-1 (5 6)Major depression (% patients)* 30 6Dysthymia (%) 27 27No depression (%) 43 67Bech mania scale (mean)t 0 2-0 (5-9)Psychosis dementia scale (mean) 1-0 (1 9) 1 7 (2-7)Functional independence measure 60-9 (12-4) 64 7 (8-0)Anosognosia quest-dementia* 2-2 (14-1) 12 1 (22-4)Irritability scale 10-4 (7-3) 12-6 (9-3)Apathyscale 17-8(79) 15-5(11-1)Pathological laughing scale 0 0 5 (2-6)Pathological crying scale 2-1 (3 7) 4-4 (5 3)Social ties checklist 3-6 (1-8) 3 4 (1-6)

Values in parentheses are SD.*P < 005; tP < 005.

Table 3 NeuropsychologicalfindingsPD dementia group AD group

Mini mental state examination 20 3 (6 5) 20-3 (6 2)Raven's progressive matrices (%)* 24 7 (23 2) 48-3 (34-1)Winconsin card sorting test (categories) 2-6 (2 1) 2-5 (2-0)Word controlled association test 28-3 (9 2) 30 7 (11-8)Buschke selective reminding test 32-3 (18-6) 28 8 (23-1)Benton visual retention test 5 0 (2-2) 5 5 (2-4)Digits forward 5-2 (1-3) 5 1 (0 9)Digits backward 3-3 (0 9) 3-2 (1-0)Purdue pegboard test-right* 6-7 (3 4) 9 7 (2 2)Purdue pegboard test-left* 6-5 (3 3) 10-0 (2-4)

Values in parentheses are SD.*p < 0 05.

than patients with Alzheimer's disease (t =2-97, df = 64, P < 0-01). Major depressionwas found in 10 patients (30%) withParkinson's disease and dementia and twopatients (6%) with Alzheimer's disease, anddysthymia was found in nine patients (27%)with Parkinson's disease and dementia andnine patients (27%) with Alzheimer's disease.A hypothesis of unequal frequency of majordepression based on the presence ofParkinson's disease-dementia or Alzheimer'sdisease was statistically substantiated (X2 =7d1, df = 2, P < 005). On the other hand,patients with Alzheimer's disease showed sig-nificantly higher AQ-D scores (more severeanosognosia; t = 2-0, df = 64, P < 0 05) andsignificantly higher mania scores thandemented patients with Parkinson's disease(t = 1-96, df = 64, P = 0 05). No significantbetween group differences were found for theremaining psychiatric variables.

NEUROPSYCHOLOGICAL FINDINGS (TABLE 3)Due to scheduling problems or patients'refusal three patients with Alzheimer's diseaseand five with dementia and Parkinson's dis-ease could only complete part of the neuropsy-chological evaluation and had to be excludedfrom the statistical analysis. However, no sig-nificant differences in age and MMSE scoreswere found between the groups withAlzheimer's disease or Parkinson's diseasewith dementia that completed the neuropsy-chological examination (age: Alzheimer'sdisease group (mean (SD) 69-9 (8 3),Parkinson's disease-dementia group 70 5(8K1) (F(1,56) = 0 07, NS); MMSE scores21-1 (5.7) v 20-0 (6 7) respectively (F(1,56)= 0 44, NS)). MANCOVA for neuro-psychological tasks (using HAM-D scores as acovariate) showed a significant main effect(Wilks' lambda = 070, df = 7,45, P < 0-05).On individual comparisons, patients withParkinson's disease and dementia had a signif-icantly worse performance on the Raven's pro-gressive matrices (F(1,51) = 8-10, P < 0.01).The Parkinson's disease with dementia groupalso showed a significantly worse performanceon the Purdue pegboard test than patientswith Alzheimer's disease (right handF(1,53) = 15-4, P < 0-001); left hand F(1,53)= 22-7, P < 0-0001). No other significantbetween group differences were found for theremaining neuropsychological tasks.

DiscussionWe compared the type and severity of cogni-tive impairments as well as the prevalence ofpsychiatric disorders in groups of patients witheither Alzheimer's disease or Parkinson's dis-ease and dementia. The groups were matchedfor age, sex, and MMSE score. Significantbetween group differences in both neuropsy-chological and psychiatric variables werenoted. Demented patients with Parkinson'sdisease had significantly more severe deficitson a task of visuospatial reasoning and per-formed more slowly on a motor task than didpatients with Alzheimer's disease. Demented

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patients with Parkinson's disease showed a sig-nificantly higher frequency of major depres-sion but patients with Alzheimer's diseaseshowed more severe anosognosia and disinhi-bition.Some limitations of our study should be

pointed out. One important issue is whetherpatients with Parkinson's disease and demen-tia may have had other psychiatric diagnoses,such as Alzheimer's disease with extrapyrami-dal signs. This is unlikely as all our dementedpatients with Parkinson's disease had a posi-tive response to levodopa, and we haverecently shown that patients with Alzheimer'sdisease with extrapyramidal signs do not haveimproved motor function after levodopa.'0Moreover, all our patients with Parkinson'sdisease and dementia had the onset of cogni-tive impairment more than one year after theonset of motor deficits. The second limitationwas that we had no neuropathological confir-mation of our clinical diagnoses, and whetherour patients with Parkinson's disease may havethe neuropathological changes of a diffuseLewy body disease cannot be ruled out.However, whereas patients with diffuse Lewybody disease usually show no or only a mildand transient response to dopaminergic ago-nists,33 our patients with Parkinson's diseaseand dementia showed a consistently positiveresponse to levodopa. McKeith et al haverecently proposed that the presence of fluctua-tion cognitive impairments affecting bothmemory and higher cortical functions, as wellas hallucinations and paranoid delusions, mildspontaneous extrapyramidal features, andrepeated unexplained falls may characterisepatients with Lewy body dementia.34 As thisneuropsychiatric syndrome usually startsbefore the onset of extrapyramidal signs, it ishighly unlikely that patients with Lewy bodydementia were included in our group withParkinson's disease and dementia. Anotherlimitation is that we assessed our patients withParkinson's disease after the intake of theirregular dose of levodopa. Although theircognitive performance might have been worsewithout levodopa, several studies could notshow significant differences in cognitive per-formance for on versus off levodopa amongpatients with Parkinson's disease.35 Thepossible influence of levodopa on behaviouralproblems such as apathy and anosognosiashould be examined in future studies. Finally, itcould be argued that among patients withParkinson's disease the HAM-D may rateextrapyramidal symptoms as depressive com-plaints. However, we showed the validity ofthe autonomic and affective symptoms ofdepression rated in the HAM-D for thediagnosis of dysthymia and major depressionin Parkinson's disease.36Cummings and Benson' suggested that cor-

tical and subcortical dementias differ in termsof motor disorders, profile of cognitive deficits,and prevalence of psychiatric disorders, but toour knowledge no systematic study of all thesevariables in the same cohort of patients hasbeen carried out. Our study offers some sup-port for the hypothesis of Cummings and

Benson: the demented group with Parkinson'sdisease showed more severe motor slowingand a higher prevalence of major depression,whereas patients with Alzheimer's diseaseshowed significantly more severe anosognosiaand disinhibition. On the other hand, betweengroup differences on neuropsychological test-ing were restricted to a single task of visuospa-tial reasoning.

Several studies have examined neuropsy-chological differences between patients withcortical and subcortical dementias (mostlyAlzheimer's disease v Parkinson's disease,Huntington's disease, or progressive supranu-clear palsy).6 - Some studies using screen-ing measures of global cognitive performancedid not find significant differences betweenpatients with cortical and subcortical demen-tias,5 but studies using more comprehensiveneuropsychological evaluations have shownsignificant between group differences.6 7 3840

Cummings et al 39 compared patients withAlzheimer's disease and demented patientswith Parkinson's disease and a similar globalseverity of cognitive impairment. They foundthat whereas patients with Alzheimer's diseasehad more severe anomia and less informationcontent in spontaneous speech, dementedpatients with Parkinson's disease had moregrammatically simplified utterances anddysarthria. Freedman and Oscar-Berman40reported greater impairment on a delayedalternation task in patients with Alzheimer'sdisease than in demented patients withParkinson's disease, but no significantbetween group differences on delayedresponse tasks. Litvan et al'8 reported moresevere deficits on tests of executive functionamong demented patients with Parkinson'sdisease, whereas patients with Alzheimer's dis-ease showed greater impairment on tasks ofsemantic and episodic memory. Similar find-ings were reported by Pillon et al.6

In the present study we found dementedpatients with Parkinson's disease to besignificantly more impaired on the Raven'sprogressive matrices than patients withAlzheimer's disease with a similar severity ofdementia. This test requires the subject toconceptualise spatial, design and numericalrelations, ranging from very concrete to veryabstract designs. Deficits in visuospatial per-ception and abstraction have been reported inpatients with Parkinson's disease even in theabsence of overt dementia,4' and it is possiblethat deficits in visuospatial reasoning are fur-ther compromised early in the dementia ofParkinson's disease. Similar findings werereported by Sahakian et a142 who found thatpatients with Parkinson's disease performedsignificantly worse than patients withAlzheimer's disease on tests of visual discrimi-nation learning and attentional set shifting.However, we did not find significant differ-ences between patients with Alzheimer's dis-ease and demented patients with Parkinson'sdisease in other cognitive domains, such asverbal and visuospatial memory, attention, setalternation, and verbal fluency. Thus differen-tial impairments in cognitive abilities in corti-

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cal and subcortical dementias are not wide-spread and may be restricted to specific cogni-tive domains. Most of our patients withAlzheimer's disease and demented patientswith Parkinson's disease were in the earlystages of the illness, which may have con-tributed to the small difference betweengroups in cognitive performance.

Whereas Cummings and Benson' suggestedthat the prevalence of depression, anosog-nosia, and disinhibition may be different incortical and subcortical dementias, to ourknowledge ours is the first study to use a struc-tured psychiatric evaluation to assess thesesymptoms in a sample of patients withAlzheimer's disease and demented patientswith Parkinson's disease matched for age, sex,and severity of dementia. We found thatwhereas major depression was significantlymore prevalent in demented patients withParkinson's disease, anosognosia, and disinhi-bition were more severe in patients withAlzheimer's disease.

In a recent study that included 103 patientswith Alzheimer's disease we found that 23%had major depression and 28% had dys-thymia.9 However, in the present study theprevalence of major depression in patientswith Alzheimer's disease was lower. This dis-crepancy may be due to differences in sex dis-tribution between the two studies. In ourprevious study 74% of the Alzheimer's diseasesample and 22 of the 24 (92%) patients withAlzheimer's disease with major depressionwere female patients. In the present study only30% of the Alzheimer's disease sample andonly four of the 10 (40%) demented patientswith Parkinson's disease with major depres-sion were female patients x2 = 10-4, df = 1,P = 0001). Thus whereas major depressionin Alzheimer's disease seems to occur signifi-cantly more often among female patients, inParkinson's disease with dementia, majordepression is more prevalent in male patients.These findings suggest that the associationbetween major depression and eitherAlzheimer's disease or Parkinson's disease anddementia may be sex related, and differencesin the prevalence of major depression betweencortical and subcortical dementias may berelated to the numbers of male and femalepatients in each group.

Another interesting finding was thatanosognosia and disinhibition were both moresevere in patients with Alzheimer's diseasethan in demented patients with Parkinson'sdisease. In a recent study we found thatanosognosia in Alzheimer's disease was signifi-cantly associated with relatively lower rightfrontal lobe perfusion,4' whereas disinhibitedbehaviour was significantly associated with rel-atively more severe bilateral orbitofrontal andbasotemporal perfusion deficits." Thus thehigher prevalence of anosognosia and disinhi-bition in patients with Alzheimer's diseasecompared with demented patients withParkinson's disease may be related to moresevere frontotemporal cortical dysfunction.

Finally, we could not find significantbetween group differences in the severity of

delusions, apathy, irritability, and emotionallability. This shows that, similar to neuropsy-chological findings, differences in psychiatricdisorders between cortical and subcorticaldementias are not widespread but may berestricted to specific psychiatric domains.

In conclusion, our study showed significantpsychiatric differences between patients withAlzheimer's disease and patients withParkinson's disease with dementia matchedfor age, sex, and severity of dementia. On theother hand, neuropsychological differenceswere mild and restricted to a single cognitivedomain. Future studies should examine theassociation between sex and psychiatric disor-ders in demented patients, and determinewhether specific deficits in cortical metabolicactivity may account for psychiatric differencesbetween cortical and subcortical dementias.

This study was partially supported by grants from the RailCarrea Institute of Neurological Research, the FundacionPerez Companc, and the CONICET. We thank Dr FredBylsma for his most helpful comments.

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