neurological correlates of depressive symptoms in alzheimer's disease and vascular dementia

Journal of Affective Disorders 53 (1999) 129–136

Research report

Neurological correlates of depressive symptoms in Alzheimer’sdisease and vascular dementia

a b c d ,*Steve Simpson , Harry Allen , Barbara Tomenson , Alistair BurnsaConsultant Psychiatrist for the Elderly, Forston Clinic, Herrison, Dorchester DT2 9TB, United Kingdom

bConsultant in Old Age Psychiatry, York House, Manchester Royal Infirmary, Manchester M13 9WL, United KingdomcStatistician, University of Manchester, Department of Psychiatry, Rawnsley Building, Manchester M13 9WL, United Kingdom

dProfessor of Old Age Psychiatry, University of Manchester, Withington Hospital, West Didsbury, Manchester M20 8LR,United Kingdom

Received 4 December 1997; received in revised form 30 April 1998; accepted 1 June 1998

Abstract

Background. Organic brain disease such as dementia or stroke is associated with depression. In dementia, depressivesymptoms are common where there is evidence of vascular disease and in Alzheimer’s disease they often coexist withextrapyramidal signs. Method. In a study of 60 patients with Alzheimer’s disease and 39 patients with vascular dementia,depressive symptoms were rated using the Cornell Scale for Depression in Dementia. Neurological signs were assessed andseverity of cognitive impairment was measured with the Mini-Mental State Examination. Results. Depressive symptomswere more severe in vascular dementia. Pyramidal tract signs had no relationship to depression in either type of dementia. Invascular dementia, extrapyramidal and grasp reflexes were strongly related to the severity of depression, and were associatedwith neurovegetative features. In Alzheimer’s disease, extrapyramidal signs were the strongest independent predictor of theseverity of depression. Conclusion. Depressive symptoms are more severe in vascular dementia compared to Alzheimer’sdisease and were related to neurological abnormalities. 1999 Elsevier Science B.V. All rights reserved.

Keywords: Alzheimer’s disease; Vascular dementia; Depression; Neurological correlates

1. Introduction dementia yet in 40% of cases it is treatable withantidepressants (Baldwin et al., 1993). Studies have

Depression in dementia is important because it is a estimated the prevalence of depression among pa-significant determinant of morbidity and is associated tients with Alzheimer’s disease (AD) at 20 to 30%with caregiver distress (Drinka et al., 1987). Clini- (Migliorelli et al., 1995; Reifler et al., 1986; Wraggecally it can be difficult to diagnose depression in and Jeste, 1989; Allen and Burns, 1995), and have

found it to be higher than in age matched controls*Corresponding author. (Lazarus et al., 1987; Rovner et al., 1989). Attempts

0165-0327/99/$ – see front matter 1999 Elsevier Science B.V. All rights reserved.PI I : S0165-0327( 98 )00103-7

130 S. Simpson et al. / Journal of Affective Disorders 53 (1999) 129 –136

to account for this increased risk of depression have severity of depression have been modest and otherfocused on three groups of risk factors – premorbid studies have found that those patients with VaDconstitutional, psychological, and biological factors. actually had lower levels of depression (Bucht et al.,Gender or previous psychiatric history, are recog- 1984; Reding et al., 1985). The depression associatednised risk factors for depression in AD (Rovner et with cerebrovascular disease may be qualitativelyal., 1989; Reifler et al., 1986; Lazarus et al., 1987). different and not necessarily reflective of a globalDepression in AD has been explained as a psycho- increase. Neurovegetative features including psycho-logical reaction to the disability of the disease (Kral, motor retardation, blunted affect, emotional with-1983). However, recent research suggests that aware- drawal, low motivation, and somatic concerns haveness of deficits is not consistently associated with been found to be more common in VaD than in ADdepression (Feher et al., 1991; Sevush and Leve, (Sultzer et al., 1993).1993; Reed et al., 1993; Simpson and Burns, 1996). Elderly patients with major depression and cere-Migliorelli et al. (1995) proposed that although brovascular disease (dubbed ‘‘vascular depression’’),dysthymia may be an emotional reaction to the have more psychomotor retardation but less agitationcognitive decline, major depression is not, and and less ideational features of depression whenpostulated that depression in dementia is more compared to other patients with major depressionrelated to biological factors. The neurodegenerative (Alexopoulos et al., 1997; Krishnan et al., 1997).changes of AD may directly cause depressive fea- Studies of post stroke depression have shown thattures by virtue of the effect of the disease in brain there is a higher risk and severity of depression whenregions that are involved in mood regulation. Two the lesion site is subcortical and nearer the lefthistological studies (Zubenko et al., 1990; Zweig et frontal pole (Starkstein et al., 1987, 1988; Robinsonal., 1988; Forstl et al., 1992) have found more et al., 1984, 1988). Thus, caudate head or frontaldepression in AD patients with brain stem nuclei pathology in AD and VaD may confer biologicaldegeneration (locus coeruleus, substantia nigra and vulnerability to certain types of affective symptoms,raphe nuclei). Furthermore, Merello et al. (1994) and studies that test this hypothesis are required. Theidentified a depressive subgroup of AD patients with aims of this study were: first, to compare affectiveextrapyramidal signs, and frontal cognitive impair- symptoms in patients with AD and VaD; and second,ment, and it was this subgroup that had increased to document the relationship between these featuresdepression. and neurological signs.

In vascular dementia (VaD) subcortical pathologyis often present in the form of leukoaraiosis (Hachin-ski et al., 1975), Binswanger’s disease or lacunar 2. Methodsstates (Cummings, 1994). Subcortical neuropsychiat-ric features dominate the clinical presentation of VaD 2.1. Sample(Wallin et al., 1991), and subcortical vascular diseaseis characterised by affective features (Cummings, Patients with AD and VaD known to the old age1994; Simpson et al., 1997). Where vascular damage psychiatry service in South Manchester were in-affects the lenticulo-striate circulation, extrapyram- cluded in the study (Lennon and Jolley, 1993).idal signs develop and have been described as the Patients had complete clinical notes and a clinical‘‘marche a petit pas’’ (Brown, 1995). VaD has been diagnosis was made according to ICD-10 criteria.traditionally associated with depression, the is-chaemic score (Hachinski et al., 1975) included 2.2. Measuresdepression as a risk factor signifying the presence ofcerebrovascular disease in patients with dementia. Patient and carer were interviewed blind to theSome studies have demonstrated more severe depres- diagnosis, using the following measures:sion in VaD compared with AD (Sultzer et al., 1993;Cooper and Mungas, 1993; Cummings et al., 1987; Cornell Scale for Depression in Dementia (CSDD,Greenwald et al., 1989). However, the differences in Alexopoulos et al., 1988). The CSDD was developed

S. Simpson et al. / Journal of Affective Disorders 53 (1999) 129 –136 131

for detecting depressive signs and symptoms and and for non-parametric data they were expressed asconsists of an interview with both patient and carer. the median with interquartile range (IQR). BivariateThe scale has five subscales from which the total correlations between non-parametric variables usedCSDD score is derived – mood related behavioural the Spearman correlation coefficient. Forward step-and physical signs, cyclic functions and ideational wise logistic regression quotes the significant im-disturbance. Patients with severe affective features provement in the model on a step by step basis atwere defined as those scoring above 7 on the CSDD, each level including the baseline. Cumulative spe-a recognised cut-off point to discriminate mild to cificity and sensitivity are also included for thesevere depression (Alexopoulos et al., 1988; Vida et significant predictors on a forward step by step basis.al., 1994). The study was approved by the local research ethics

committee

Mini-Mental State Examination (MMSE, Folsteinet al., 1975). The MMSE gives a measure ofcognitive impairment on a 30 point scale.

3. Results

2.3. Neurological assessment Sixty patients with AD and 39 with VaD wereassessed. In addition, 8 patients were defined as

A standardised neurological examination for focal having Lewy body dementia, (McKeith et al., 1994)pyramidal tract signs (power, deep tendon reflexes but were not included in the sample because of theand plantar reflex), frontal release phenomena small number. The number of patients completing(primitive grasp reflex), and extrapyramidal signs each part of the assessment varied slightly (see tablesbased on the Webster scale (Webster, 1968) was and text). Reliability for assessment of neurologicalcarried out. The Webster Scale contains 10 items signs was: grasp reflex, Kappa 5 0.85; pyramidalmeasured on a four-point severity scale of 0–3, signs, Kappa 5 0.82; and extrapyramidal signs,including a rating of speech and self-care. In view of Kappa 5 0.80.the fact that these two items could be rated highly inpeople with moderate to severe dementia in theabsence of extrapyramidal signs, they were omitted 3.1. Clinical features of the dementia sampleand replaced with two items from the UnifiedParkinson’s disease Rating Scale (Fahn Elton, 1987) Table 1 summarises the clinical features of the– balance and rising from a chair, rated on the same sample. There was a trend for the VaD group to benumerical scale. Thus, the severity of neurological older and there were more women (P 5 0.021) in thesigns were rated on a 10 point scale with a possible AD group. The differences in the Hachinski scorescore of 0–30. Neuroleptic mediation at the time of confirmed the clinical differentiation between ADthe neurological examination was recorded and and VaD.converted to milligram equivalents of chlor-promazine (WHO, 1994).

3.2. Comparison of depression between AD and2.4. Statistics VaD

Statistics were analysed using SPSS for windows The severity of and prevalence of depressionversion 6.1. Categorical variables were compared defined as a CSDD score . 7 were greater in VaDusing the Chi-square test. Significant between group than AD (P 5 0.048 and P 5 0.046 respectively,differences were determined using the Mann-Whit- Table 2). However, of the subscales of depressiveney U test for non-parametric data, and the t-test for symptoms, behavioural features were the only sub-parametric data. For parametric data descriptives type that was significantly increased (Mann-Whitneywere expressed with the mean and standard deviation v test, P 5 0.0052) in VaD compared with AD.


Table 1Clinical characteristics of the AD and VaD groups

Clinical variables Alzheimer’s Vascular Significance ofdisease n 5 60 dementia n 5 39 difference

Mean age (yrs, SD) 77.4 (9.7) 80.3 (4.6) P 5 0.066Sex (% female) 43 (70.5%) 18 (46.1%) P 5 0.021Mini-mental state 6.8 (5.8) 7.4 (6.7) P 5 0.59examination (SD median)Neurological signs score* 5 (0–11) 5 (2–16) P 5 0.24interquartile rangeHachinski score (mean) 2.9 6.4 P 5 , 0.01

*, See text for details.Note: Significant differences were calculated using the t-test for unequal variance or Fisher’s exact test.

Table 2The comparison of depressive features (Cornell Scale) between Alzheimer’s disease and vascular dementia, Mann-Whitney

Cornell score Alzheimer’s Vascular Significancedisease n 5 57 dementia n 5 36 (Mann-Whitney v test)

Mood related signs 1 (0.3) 2 (0.3) P 5 0.18Behavioural features 0 (0–2) 2 (0–3) P 5 0.0052Physical signs 0 (0–1) 1 (0–2) P 5 0.15Cyclic functions 0 (0–1) 0 (0–1) P 5 0.31Ideational disturbance 0 (0–0) 0 (0–0) P 5 0.68Total Cornell score 3 (0–7) 7 (3–8) P 5 0.048Cases of mild depression 28.1% (16) 50% (18) P 5 0.046

Note: Medians are expressed with the interquartile range in parentheses.

3.3. Extrapyramidal correlates of depression In the AD group, extrapyramidal signs correlated(P 5 0.020) with severity of depression, but of the

These are summarised in Table 3. The AD and mood subscales of the CSDD, only physical features,VaD did not differ in terms of the association of (anorexia, weight loss and fatiguebility) of depres-affective symptoms and age or severity of cognitive sion correlated significantly (P 5 0.023) with extra-impairment. There was no significant correlation pyramidal signs. However, there were trends for thebetween extrapyramidal signs and milligram equiva- subscales of behavioural signs (agitation, retardation,lents of chlorpromazine in the whole sample. multiple physical complaints and loss of interest,

Table 3Extrapyramidal signs, age, and MMSE correlates (Spearman) of Cornell Scale scores

Correlation Alzheimer’s disease Vascular dementia

Age MMSE Extrapyramidal Age MMSE Extrapyramidal(n 5 57) (n 5 56) signs (n 5 47) (n 5 36) (n 5 34) signs (n 5 28)

Mood-related signs 2 0.07 2 0.12 0.26 2 0.28 2 0.23 2 0.13Behavioural disturbance 2 0.16 2 0.25 0.29 2 0.18 2 0.10 0.55***Physical signs 2 0.18 2 0.25 0.33* 2 0.09 2 0.28 0.54***Cyclic functions 2 0.13 2 0.022 0.02 2 0.12 2 0.20 0.04Ideational disturbance 2 0.04 2 0.04 0.04 2 0.26 0.12 2 0.34Total Depression Score 2 0.15 2 0.23 0.34* 2 0.29 2 0.11 0.39*

*, P , 0.05.***, P , 0.005.


P 5 0.051), and mood related signs (anxiety, sad- the prediction of depression was moderate (50%) butness, lack of reactivity and irritability) to be associ- highly specific (88.4%).ated (P 5 0.080) with more severe extrapyramidal The AD and the VaD groups were studied separ-signs. ately using the same statistical model. In AD (n 5 46

In the VaD group there were strong correlations included in the analysis) the overall baseline chancebetween extrapyramidal signs and both behavioural prediction of depression was 67.4%. Extrapyramidal(r 5 1 0.55, P 5 0.002) and physical features of signs independently improved the prediction of

2depression (r 5 1 0.54, P 5 0.003). A trend depression (x 5 5.3, P 5 0.022) with weak sen-emerged showing that the more severe the extra- sitivity (40%) but very high specificity (90.3%). Inpyramidal disease, the less severe the ideational VaD (n 5 25 included in the analysis), the overalldisturbance (suicidal ideation, poor self esteem, baseline chance prediction of depression was 52%pessimism and delusions) (r 5 2 0.34, P 5 0.080). and this was significantly improved by the presence

of a grasp reflex which was the strongest indepen-23.4. Frontal release and pyramidal tract signs dent predictor of depression (x 5 13.4, P 5

0.00037) and had a moderately high sensitivityThe severity of extrapyramidal disease was higher (76.9%) and a very high specificity (91.7%). Fur-

2(Mann-Whitney U test, P , 0.00001) in patients with thermore, younger age (x 5 6.2, P 5 0.013) and2a grasp reflex (median 5 19, IQR 5 13–24) com- less cognitive impairment on the MMSE (x 5 10.0,

pared with those with absent grasp reflexes P 5 0.0015) significantly increased the sensitivity of(median 5 2, IQR 5 0–5). In AD, focal pyramidal the prediction to 92.3%.weakness (P 5 0.66), abnormality of tendon reflexes(P 5 0.90), and up going plantar reflex (P 5 0.92),were not related to the severity of depression. In VaDpyramidal signs bore no significant relation to the 4. Discussionseverity of depression (Mann Whitney; P 5 0.09;P 5 0.69; P 5 0.67). In AD the pressure of a grasp The main findings of this study were: depression isreflex was not related to severity of depression (P 5 more common and more severe in VaD than AD;0.12) or any of the affective subscales. In VaD, a compared with AD, patients with VaD have morepositive grasp reflex was significantly related to a neurovegetative features; extrapyramidal signs weregreatly increased total severity of depression (P 5 the strongest independent predictor of depression in0.009), in addition to the behavioural (P 5 0.001), the sample and extrapyramidal signs and frontalphysical (P 5 0.046) and cyclic (P 5 0.025) sub- neurological signs were strongly associated withscales of affective symptoms. depressive symptoms in VaD.

In the patients with AD the estimated prevalence3.5. Predictors of depression of depression was 28%. This is consistent with other

studies, which have estimated the prevalence ofA forward stepwise logistic regression equation depression in AD at 23% (Migliorelli et al., 1995).

was carried out, with depression as the dependent In the present study depression was more common invariable (n 5 71). Severity of cognitive impairment VaD (50%), and this finding confirms the general(MMSE), sex, age, extrapyramidal signs, grasp view that depressive symptoms are more commonreflexes, type of dementia (VaD) and plantar reflexes and severe in VaD than AD (Cooper and Mungas,were the independent predictors of depression. 1993; Sultzer et al., 1993). Sultzer et al. (1993) usedBaseline chance correct prediction of depression was a smaller number of patients with mild dementia to60.6%. Only two features had independent improve- show a slightly higher mean Hamilton Depressionments on the chance predictions of depression in Rating Scale score (Hamilton, 1960) in the vascular

2dementia. These were extrapyramidal disease (x 5 compared with the AD group. This difference al-215.8, P 5 0.00015), and younger age (x 5 4.5, P 5 though of little clinical magnitude, was significant.

0.034). For extrapyramidal signs the sensitivity of Sultzer et al. (1993), also found that compared with


AD, depression in vascular dementia was character- Whether these symptoms represent pseudodepressiveised by more neurovegetative features. features of neurological disease (abulia), or whether

Focal neurological signs are one of the main risk extrapyramidal disease confers biological vul-factors used in support of a diagnosis of cerebrovas- nerability to depressive illness is unclear. Given thatcular disease in patients with dementia (Hachinski et only certain patterns of affective symptoms corre-al., 1975). However, focal pyramidal tract signs were lated with neurological signs and that ideationalnot related to affective symptoms in this study which features of depression were diminished in relation toprobably reflects the sample from which the groups extrapyramidal disease, perhaps neurological diseasewere drawn ie from an old age psychiatry service plays a role in the regulation of affective symptom inrather than a geriatric medicine service. In VaD, patients with brain disease. There are difficulties inprimitive grasp reflexes were more clearly related to the interpretation of depression symptoms in de-the severity of affective symptoms than in AD. This mentia as they (in particular behavioural distur-was especially so for the behavioural, physical and bances) may by directly related to the dementiacyclic affective symptoms, but not for the mood or itself. Our study was not able to tease out thisideational affective features. Grasp reflexes in VaD aetiologic contribution and further treatment studiesmay not be primarily due to frontal lobe disease but are needed to help resolve this issue. In ‘‘vascularcould be secondary to disruption of afferent frontal depression’’ (Alexopoulos et al., 1997; Krishnan etcircuits (Albert et al., 1974) caused by subcortical al., 1997), a type of major depression characteriseddisease. The present finding of the very strong by subcortical vascular changes, patients experiencerelationship between grasp reflexes and extrapyram- reduced feelings of guilt (Alexopoulos et al., 1997).idal signs would support this explanation. The current study provides evidence that subcortico-

In VaD grasp reflex was the strongest independent frontal neurological disease regulates affective symp-predictor of depression and in AD extrapyramidal toms in dementia and that this phenomenon maysigns were the main risk factor. Grasp refelexes in need to be considered in the classification of depres-AD were not related to depression. This may be sion in dementia.because in AD degeneration of the parietal lobes, an The finding of the negative associations betweenarea not involved in mood regulation, may have led depression and age and severity of cognitive impair-to de-afferentation of the frontal lobes via parieto- ment was the only other significant finding. Elderlyfrontal pathways (Ropper, 1982). Despite the differ- patients may have been less depressed because of theence in affective symptoms between VaD and AD under-reporting of depression (Lyness et al., 1995).with respect to primitive release phenomena, in both However, the use of an informant-based approachtypes of dementia extrapyramidal signs correlated mitigates against this bias. The limitations of thewith the severity of depressive symptoms, although current work are that types of dementia were notthis relationship was much stronger in VAD than AD. confirmed at post mortem and that the numbers ofIn VaD, although cortical infarctions are common, pateints completing some of the assessments variessubcortical neuropsychiatric features predominate slightly.(Wallin et al., 1991). The increase in depressive In conclusion, although affective symptoms arefeatures may be because VaD is predominantly a more common in VaD than AD, it is the extrapyram-subcortical disorder (Wallin et al., 1991). Subcortical idal component of the disease which accounts for thedementias have been described with greater depres- affective disturbance rather than the type of de-sive features when compared with patients with mentia. While extrapyramidal and frontal signs arecortical dementias (Cummings, 1986, 1994; Starks- sensitive and specific predictors of depression intein et al., 1996), and this is probably because vascular dementia, frontal signs are not predictive offronto-striatal circuits are thought to be important in depression in AD and extrapyramidal signs havethe regulation of mood (Mayberg et al., 1992; Austin high specificity but low sensitivity for predictingand Mitchell, 1995). depression in AD. Finally, extrapyramidal features

Behavioural features (as defined in the CSDD) and frontal cerebrovascular neurological impairmentcorrelated most strongly with extrapyramidal signs. are associated with an increase of behavioural and


Fahn Elton, R., 1987. Recent developments in Parkinsons’ dis-physical affective symptoms, but a reduction inease, Volume 3. MacMillan Healthcare Information, USA, pp.ideational features of depression.153–163.

Feher, E.P., Mahurin, R.K., Inbody, S.P., Crook, T.H., Pirozzolo,F.J., 1991. Anosagnosia in Alzheimer’s disease. Behav. Neurol.4, 136–146.Acknowledgements

Folstein, M.F., Folstein, S.E., McHugh, P.R., 1975. Mini mentalstate: a practical method for grading the psychiatric state ofWe are grateful to Dr Sean Lennon and Dr Janepatients for the physician. J. Psychiatr. Res. 12, 189–198.

Byrne for allowing us to examine people under their Forstl et al., 1992. Clinical and neuropathological correlates ofcare, and to the patients and their relatives who depression in Alzheimer’s disease. Psychol. Med. 22, 877–884.

Greenwald, B.S., Kramer-Ginsberg, E., Marin, D.B., Herman,participated in the study.C.K., Mohs, R.C., Davis, K.L., 1989. Dementia with majordepression. Am. J. Psychiatry 146, 1472–1481.

Hachinski, V.C., Liff, L.D., Zilkha, E., et al., 1975. Cerebral bloodReferences flow in dementia. Arch. Neurol. 32, 632–637.

Hamilton, M., 1960. A rating scale for depression. J. Neurol.Neurosurg. Psychiatry 23, 56–62.Albert, M.L., Friedman, R.G., Willis, A.L., 1974. The subcortical

Kral, V., 1983. The relationship between senile dementia anddementia of progressive supranuclear palsy. J. Neurol. Neuro-depression. Can. J. Psychiatry 28, 304–306.surg. Psychiatry 37, 121–130.

Krishnan, K.R.R., Hays, J.C., Blazer, D.G., 1997. MRI-definedAlexopoulos, G.S., Abrams, R.C., Young, R.C., Shamoian, C.A.,vascular depression. Am. J. Psychiatry 154, 497–501.1988. Cornell scale for depression in Dementia. Biol. Psychi-

Lazarus, L.W., Newton, N., Cohler, B., Lesser, J., Schweon, C.,atry 23, 271–284.1987. Frequency and presentation of depressive symptoms inAlexopoulos, G.S., Meyer, B.S., Young, R.C., Kakuma, T.,patients with degenerative dementia. Am. J. Psychiatry 144,Silbersweig, D., Charlson, D., 1997. Clinically defined vascular542–550.depression. Am. J. Psychiatry 154, 562–565.

Lennon, S., Jolley, D., 1993. Psychiatry in the elderly: An urbanAllen, N.H.P., Burns, A.S., 1995. Non-cognitive features ofservice. In: Jacoby, R., Oppenheimer, C. (Eds.), Psychiatry indementia. Rev. Clin. Gerontol. 5, 25–75.the Elderly. Oxford University Press, Oxford, pp. 322–339.Austin, M., Mitchell, P., 1995. The anatomy of melancholia: does

Lyness, J.M., Cox, C., Curry, J., Conwell, Y., King, D., Caine, E.,frontal-subcortical pathophysiology underpin its psychomotor1995. Older age and the under-reporting of depressive symp-and cognitive manifestations? Psychol. Med. 25, 665–672.toms. J. Am. Geriatr. Soc. 43, 216–221.Baldwin, R.C., Benbow, S.M., Marriott, A., Tomenson, B., 1993.

Mayberg, H., Starkstein, S.E., Peyser, C.E., Brandt, J., Dannals,The prognosis of depression in later-life: a reconsideration ofR.F., Folstein, S.E., 1992. Paralimbic frontal lobe hypo-cerebral organic factors in relation to outcome. Br. J. Psychi-metabolism in depression associated with Huntington’s disease.atry 163, 82–90.Neurology 42, 1791–1797.Brown, M., 1995. Subcortical vascular dementia in perspective.

McKeith, I.G., Fairburn, A.F., Bothwell, R.A., 1994. An evalua-In: Levy, R., Howard, R. (Eds.), Developments in Dementiation of the predictive validity and inter-rater reliability ofand Functional Disorders in the Elderly, 4. Wrightson Bio-clinical diagnostic criteria for senile dementia of the Lewymedical, London, pp. 31–42.Body type. Neurology 44, 872–877.Bucht, G., Adolfsson, R., Winblad, B., 1984. Dementia of the

Merello, M., Sabe, L., Teson, A., et al., 1994. ExtrapyramidalismAlzheimer’s type and multi-infarct dementia: a clinical descrip-in Alzheimer’s disease: prevalence, psychiatric, and neuro-tion and diagnostic problems. J. Am. Geriatr. Soc. 32, 491–psychological correlates. J. Neurol. Neurosurg. Psychiatry 57,499.1503–1509.Cooper, J.K., Mungas, D., 1993. Risk factor and behavioural

Migliorelli, R., Teson, A., Sabe, L., Petracchi, M., Leiguarda, R.,differences between vascular and Alzheimer’s dementias: TheStarkstein, S., 1995. Prevalence and correlates of major depres-pathway to end stage disease. J. Geriatr. Psychiatry Neurol. 6sion and dysthymia among patients with Alzheimer’s disease.(1), 29–33.Am. J. Psychiatry 152, 37–44.Cummings, J.L., 1986. Subcortical dementia. Br. J. Psychiatry

Reding, M., Haycox, J., Blass, J., 1985. Depression in Patients in149, 682–697.a dementia clinic. Arch. Neurol. 42, 894–896.Cummings, J.L., 1994. Vascular subcortical dementia: Clinical

Reed, B.R., Jagust, W.J., Coulter, L., 1993. Anosagnosia inaspects. Dementia 5, 177–180.Alzheimer’s disease relationship to depression cognitive func-Cummings, J.L., Miller, B., Hill, M.A., Neshkes, R., 1987.tion and cerebral perfusion. J. Clin. Exp. Neuropsychol. 15,Neuropsychiatric aspects of multi-infarct dementia and de-231–244.mentia of the Alzheimer’s type. Arch. Neurol. 44, 389–393.

Drinka, T.J.K., Smith, J.C., Drinka, P.J., 1987. Correlates of Reifler, B.V., Larson, E., Teri, L., Poulsen, M., 1986. Dementia ofdepression and burden for informal caregivers of patients in a the Alzheimer’s type and depression. J. Am. Geriatr. Assoc. 34,geriatrics referral clinic. J. Am. Geriatr. Soc. 35, 522–525. 855–859.


Robinson, R.G., Kubos, K.L., Starr, L.B., 1984. Mood disorders in Sultzer, D.L., Levin, H.S., Mahler, M.E., High, W.M., Cummings,post stroke patients; importance of lesion location. Brain 107, J.L., 1993. A comparison of psychiatric symptoms in vascular81–93. dementia and Alzheimer’s disease. Am. J. Psychiatry 150,

Robinson, R.G., Starkstein, S.G., Price, T.R., 1988. Post stroke 1806–1812.depression and lesion location. Stroke 19, 125–126. Vida, S., Des-Rosiers, P., Carrier, L., Gauther, S., 1994. Depres-

Ropper, A.H., 1982. Self grasping: a focal neurological sign. Ann. sion in Alzheimer’s disease: Receiver operating characteristicNeurol. 12 (6), 575–577. analysis of the Cornell Scale for depression in dementia and the

Rovner, B.W., Broadhead, J., Spencer, M., Carson, K., Folstein, Hamilton depression scale. J. Geriatr. Psychiatry Neurol. 7,M.F., 1989. Depression in Alzheimer’s disease. Am. J. Psychi- 159–162.atry 146, 350–353. Wallin, A., Blennow, K.A.J., Gottfries, C.G., 1991. Subcortical

Sevush, S., Leve, N., 1993. Denial of memory deficits in symptoms predominate in vascular dementia. Int. J. Geriatr.Alzheimer’s disease. Am. J. Psychiatry 150, 748–751. Psychiatry 6, 137–145.

Simpson, S., Burns, A., 1996. Alzheimer’s disease; Neuro- Webster, D.D., 1968. Critical analysis of the disability in Parkin-psychiatry. Curr. Opin. Psychiatry 9, 89–92. son’s disease. Mod. Treatment 5, 257–282.

Simpson, S., Talbot, P., Snowden, J., Neary, D., 1997. Neuro- WHO, 1994. World Health Organisation Collaberative Centre forpsychiatric features of subcortical vascular dementia presenting Drug Statistics Methodology: Guidelines for Daily Drug Doses.with resistant depression. J. Neurol. Neurosurg. Psychiatry 62, World Health Organisation, Oslo Norway.196–197. Wragge, R.E., Jeste, D.V., 1989. Overview of depression and

Starkstein, S.E., Robinson, R.G., Price, T.R., 1987. Comparison of psychosis in Alzheimer’s disease. Am. J. Psychiatry 146, 577–cortical and subcortical lesions in the production of post stroke 587.mood disorders. Brain 110, 1045–1059. Zubenko, G.S., Moosey, J., Koop, U., 1990. Neurochemical

Starkstein, S.E., Robinson, R.G., Price, T.R., 1988. Comparison of correlates of major depression in primary dementia. Arch.patients with and without post stroke depression matched for Neurol. 47, 209–214.size and lesion location. Arch. Gen. Psychiatry 45, 247–252. Zweig, R., Ross, C.A., Hedreen, J.C., 1988. The neuropathology

Starkstein, S.E., Sabe, L., Petracca, G., et al., 1996. Neuro- of the aminergic nuclei in Alzheimer’s disease. Ann. Neurol.psychological and psychiatric differences between Alzheimer’s 24, 233–242.disease and Parkinson’s disease with dementia. J. Neurol.Neurosurg. Psychiatry 61, 381–387.

neurological correlates of depressive symptoms in alzheimer's disease and vascular dementia

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