Primitive reflexes in cerebrovascular disease: a community study of older people with stroke and carotid stenosis

PRIMITIVE REFLEXES IN CEREBROVASCULARDISEASE: A COMMUNITY STUDY OF OLDER

PEOPLE WITH STROKE AND CAROTID STENOSISRAHUL RAO1*, STEPHEN JACKSON2 AND ROBERT HOWARD3

1Senior Registrar, Department of Old Age Psychiatry, Maudsley Hospital and Institute of Psychiatry, London, UK2Professor, Department of Health Care of the Elderly, King's College School of Medicine and Dentistry,

Dulwich Hospital, London, UK3Senior Lecturer, Department of Old Age Psychiatry, Institute of Psychiatry, London, UK

SUMMARY

Objectives. To determine the prevalence of primitive re¯exes ( frontal release signs) in elderly community residentswith cerebrovascular disease and to examine their relationship with neuropsychological and mood-related variables.

Methods. Three groups of 25 people over 65 with anterior circulation stroke, transient ischaemic attack (TIA) and acontrol group were assessed using measures of generalized cognitive impairment, frontal lobe dysfunction, frontalrelease signs and mood-related variables. Predictors of cerebrovascular disease were examined further in stroke andTIA groups.

Results. Both stroke and TIA groups showed a higher mean score on the Frontal Release Signs Scale and a higherprevalence of most re¯exes than the control group. Verbal ¯uency and DSM-IV depressive disorder were independentpredictors of frontal release signs.

Conclusion. TIAs may predispose to subtle neurological impairment, which may be mediated by frontal lobedamage. Their role in the pathogenesis of depression in later life requires further exploration. Copyright# 1999 JohnWiley & Sons, Ltd.

KEY WORDSÐprimitive re¯exes; frontal lobe; stroke; TIA; carotid stenosis; depression; suicide

There is currently a growing awareness thatcerebrovascular disease may become manifest ina neurologically `silent' manner, with resultingchanges in cognitive function (Price et al., 1997;Zito et al., 1996) or mood (Fujikawa et al., 1993)rather than gross sensory/motor impairment.These `hard' neurological signs may be replacedwith `soft' signs that are detectable on closerexamination.

The most frequently studied soft signs are stereo-typed motor responses to speci®c stimuli, morecommonly known as primitive re¯exes. These aregenerally thought of as sequelae of frontal lobedea�erentation or `release' as a result of di�usecortical dysfunction, hence the term `frontal releasesigns' (Franssen et al., 1993). Primitive re¯exes

have been examined in both Alzheimer's diseaseand vascular dementia (Hogan and Ebly, 1995;Vreeling et al., 1995); they also have a recognizedassociation with subcortical infarction (Corbettet al., 1992). However, less is known about theirpresence following transient cerebrovascularischaemia, which may result in subtle organicbrain damage per se.

OBJECTIVES

The main aim of the study was to compare theprevalence of primitive re¯exes between olderpeople with symptomatic cerebrovascular diseaseand a control group. The main hypothesis to betested was that primitive re¯exes were more likely tobe present in peoplewith both completed stroke andtransient ischaemic attacks (TIA) than in a controlgroup. Predictors of the presence of primitive

CCC 0885±6230/99/110964±09$17.50 Received 3 March 1999Copyright # 1999 John Wiley & Sons, Ltd. Accepted 20 May 1999

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY

Int. J. Geriat. Psychiatry 14, 964±972 (1999)

*Correspondence to: Dr R. Rao, Job Ward, Thomas GuyHouse, Guy's Hospital, London SE1 9RT, UK. Tel: 0171-232-0148. Fax: 0171-394-1097. E-mail: [email protected]

re¯exes were also examined in the presence ofcerebrovascular disease.

METHODOLOGY

The sampling frame comprised two groupsof 50 community residents with cerebrovasculardisease (CVD) (25 with stroke and 25 with TIA)and a group of 25 controls, all drawn from an innercity population.

Stroke group

The stroke group consisted of 25 consecutiveinpatients who had been admitted to an acutestroke unit and later transferred to one of twopossible stroke rehabilitation wards. Only peoplesu�ering their ®rst stroke in the anterior circulationdistribution (con®rmed by both clinical and radio-logical examination) were selected. All patientswere interviewed between 6 months and a year aftertheir admission to the stroke unit.

Transient ischaemic attack (TIA) group

The TIA group constituted 25 people withcarotid stenosis on the waiting list for carotidendarterectomy. Consecutive patients were chosen,all of whom had su�ered one or more transientischaemic attack and showed at least 70% stenosisof one/both carotid arteries on doppler ultrasound.Patients with a history of stroke or clinical evidenceof stroke during preoperative screening wereexcluded.

For both vascular groups, participants wereselected if they were still residing in the hospital'scatchment area and were 65 or over at time ofinterview. Those people who had su�ered a furtherstroke, those with evidence of peripheral vasculardisease as well as those with a history ofdrug/alcohol misuse, Parkinson's disease, headinjury, epilepsy, carcinomatosis or uncontrolledmetabolic/endocrine/respiratory disorders wereexcluded from the study.

Control group

The control group included people who hadundergone elective total hip or knee replacementsfor osteoarthritis, who, like the stroke group,had undergone a period of rehabilitation. Allwere community residents selected from the same

catchment area as the CVD groups and were 65 orover at the time of their elective total hip/kneereplacement, which had been performed between6 and 12 months prior to interview. Patients wereexcluded if they had a history of stroke, transientischaemic attacks or peripheral vascular disease.Other exclusion criteria were the same as the CVDgroups.

After the initial screening procedure for thethree groups, general practitioners (GPs) were sentan introductory letter and copy of the patientinformation sheet. In each case, GPs were con-tacted a week later and documentation was made ofpatients whose GP refused for the patient to beinterviewed and those people considered by theirGP to be too frail/cognitively impaired/uncommu-nicative. People who had died or moved out of thehospital catchment area since the study had begunwere also excluded.

People agreeing to participate were excluded ifthey were considered by the interviewer to be toofrail, severely cognitively impaired, aphasic orlacked su�cient comprehension of the Englishlanguage to be suitable for interview. Documen-tation was made of patients in each group who hadbeen excluded from the study as a result of theabove criteria, after initial patient selection. Severecognitive impairment was de®ned according toboth clinical impression and a score of 10 or less ontheMini-Mental State Examination (Folstein et al.,1975). The study was approved by the King'sCollege Hospital Local Research Ethics Commit-tee. All participants were interviewed by RR intheir place of residence after gaining writteninformed consent.

INSTRUMENTS

Rating scale for the examination of frontalrelease signs (FRSS)

A scale examining primitive re¯exes, comprisingnine operationally de®ned items, each on a seven-point semi-quantitative scale. Points 1, 3, 5 and 7are well de®ned, with 2, 4 and 6 being intermediatescores (Franssen, 1991). The nine re¯exes assessedare paratonia, as well as palmomental, hand grasp,foot grasp, glabellar, rooting, snout and visual/tactile sucking re¯exes. The scale has a high sensiti-vity and negative predictive value in di�erentiatingpatients with mild cognitive impairment from cog-nitively unimpaired older people (Franssen, 1991).

Copyright # 1999 John Wiley & Sons, Ltd. Int. J. Geriat. Psychiatry 14, 964±972 (1999)

PRIMITIVE REFLEXES IN STROKE AND CAROTID STENOSIS 965

Neuropsychological assessment

Trailmaking test. An observer-rated test ofpsychomotor speed, having high speci®city andsensitivity in the detection of organic brain damage(Reitan, 1958), particularly prefrontal dysfunction.The test is administered in two parts (A and B).Each part consists of 25 circles drawn on one sideof a piece of A4 paper. In part A, each circle isnumbered from 1 to 25 and the subject is asked todraw a line that connects the numbers in ascendingorder without lifting his/her hand from the paper.In part B, 12 circles contain the letters A±L and13 circles contain the numbers 1±13. The subject isasked to draw a line connecting the circles, startingwith number 1 and alternating a number with aletter in ascending alphabetical and numericalorder.

Each test is preceded by a practice test, so thatthe subject is familiar with the procedure. Bothtests are timed and errors corrected by theexaminer, with these corrections included in thetotal time taken to complete the test.

The Behavioural Dyscontrol Scale. A nine-itemobserver-rated scale having a maximum score of20 points. The scale is a measure of the degree ofindependent regulation in behaviour in elderlypeople (Grigsby et al., 1992). It is known to beassociated with both impulsivity and caregiverratings of disinhibition, and draws upon aspectsof frontal lobe functioning. It comprises sevennovel/repetitive motor and one verbal task, as wellas assessing the patient's insight into the existence,nature and severity of errors in performance.

Controlled word association test. Verbal ¯uency isdiminished after frontal lobe (particularly domi-nant prefrontal) damage (Benton, 1968). This testrequires the respondent to generate as many wordsas possible (excluding names and proper nouns),beginning with the letters `F', À' and `S'. In eachcase, the number of words generated within 1minute is assessed (Benton and Hamsher, 1989). Inthe present study, adding the total number ofwords generated in each category derived a total`verbal ¯uency score'.

CAMCOG Scale. A 60-item observer-rated scalecomprising a detailed cognitive examination drawnfrom the Cambridge Mental Disorders of theElderly Examination (CAMDEX) (Roth et al.,1986). The scale covers orientation, attention,language, memory, calculation, abstract thinking,

praxis and recognition, with a maximum score of107. A cuto� value of 79 and below has been foundto discriminate well between demented and non-demented individuals (Roth et al., 1986), but thismay be too high in community residents, where acuto� value of 69 performs better (Brayne andCalloway, 1990).

Assessment of mood

The Hamilton Rating Scale for Depression(HRSD) (Hamilton, 1960) and 15-item GeriatricDepression Scales (Sheik and Yesavage, 1986) wereadministered; other mood-related variables werethe presence/absence of DSM-IV major depressivedisorder, family history of depression, wish to dieand suicidal ideation within the past year. Thecriteria for DSM-IV depressive disorder (AmericanPsychiatric Association, 1994) were modi®ed forthe purposes of this study, with criterion D(`symptoms are not due to direct physiologicale�ects of a general medical condition') omittedfrom the diagnostic criteria, as stroke was likely tobe an aetiological factor.

Other measures

Social disadvantage arising from disability in aparticular domain of daily living (handicap) wasassessed using the London Handicap Scale. Thescale was developed for use in stroke populations,and shows acceptable test±retest reliability andconstruct validity against recognized disabilityassessment scales (Harwood et al., 1994). Thelevel of social support was examined with a socialsupport scale adapted from an epidemiologicalstudy (Gospel Oak study) of dementia, depressionand activity limitation in an inner city elderlypopulation (Livingston et al., 1990).

Age, sex, educational attainment, marital status,residence, social class according to the RegistrarGeneral's classi®cation (Blane, 1982), handedness,race, blood pressure and chronic physical illness (ona scale adapted from the Gospel Oak study) wererecorded. Any reported deterioration in cognitivefunction ( from either general practitioners orhospital notes) was noted for all participants.

DATA ANALYSIS

Data were analysed using the Statistical Packagefor the Social Sciences (SPSS/PC � 4.0) (Norusis,1980). The chi-squared (w2) statistic was applied to


966 R. RAO, S. JACKSON AND R. HOWARD

categorical data, with Yates's correction appliedappropriately. In the analysis of ordinal numericaldata such as scale scores, the Mann±Whitney Ù'test was used.

For the application of logistic regressionanalysis, age, systolic/diastolic blood pressures,trailmaking A/B test times, verbal ¯uency andscores on social support, handicap, physical illness,behavioural dyscontrol and frontal release signsscales were categorized according to whether theywere below or at/above the 50th percentile of thescore for each group. GDS and HRSD scores werealso recategorized in the same manner. Variableswith more than one degree of freedom (maritalstatus, social class, race, side of stroke/carotidlesion) were recoded into binary variables asfollows: married (0)/other (1); social class 1 or 2(0)/other (1); Caucasian origin (0)/other (1); right-sided lesion (0)/left-sided lesion (1). For eachgroup, variables with a p value of 40.1 were thenentered into the logistic regression equation, withthe recategorized FRSS binary value as thedependent variable.

Variables were considered independent predic-tors of FRSS score if they showed an acceptablegoodness of ®t and did not alter the likelihood ratioof other variables entered into the equation bymore than 20%.

RESULTS

Seventy-®ve patients (50 CVD and 25 controls)were interviewed. Forty-two patients were ap-proached but not interviewed, owing to deathssince the time of stroke, refusals, moves away fromthe study catchment area since the study hadbegun, physical frailty detected at interview andsevere cognitive impairment. No patient withoutsevere cognitive impairment exhibited dysphasia/aphasia severe enough to warrant exclusion fromthe study and no patient demonstrated impairedcommunication as a result of poor comprehensionof English. Twenty-three stroke patients weredescribed as having partial anterior circulationstroke and only two total anterior circulationstroke. Only one patient (stroke group) did notcomplete the CAMCOG; this was because of poorvision that also resulted in an inability to completeboth trailmaking tests. There was no reporteddeterioration in cognitive function from eithergeneral practitioners or hospital notes prior tointerview for all interviewees.

Comparisons of sociodemographic data andphysical variables were made between combinedCVD groups and the control group. There were nodi�erences in age (Mann±Whitney Ù' � 81.5,p � 0.5) or sex (w2 � 0.8, df � 1, p � 0.4) betweenCVD and control groups for people excludedfrom the study. For interviewees, there wereno di�erences between groups for age (Mann±Whitney Ù' � 604.0, p � 0.8), sex (w2 � 0.5,df � 1, p � 0.5), marital status (w2 � 1.0, df � 3,p � 0.8), racial origin (w2 � 0.3, df � 2, p � 0.8),social class (w2 � 7.4, df � 4, p � 0.1), place ofresidence (w2 � 3.9, df � 3, p � 0.3) or handed-ness (w2 � 0.0, df � 1, p � 1.0).

Severity of handicap (Mann±WhitneyÙ' � 528.5, p � 0.3), level of social support(Mann±Whitney Ù' � 493.5, p � 0.1) and socialclass (Mann±Whitney Ù' � 510.5, p � 0.2) alsoshowed no di�erences between groups.

Severity of chronic physical illness (Mann±Whitney Ù' � 510.5, p � 0.2) showed no di�er-ence between groups, but the CVD group hadhigher mean systolic (Mann±Whitney Ù' � 318.0,p � 0.0005) and diastolic (Mann±Whitney Ù' �458.0, p � 0.05) blood pressures than the controlgroup.

Primitive re¯exes

The stroke group showed a higher mean score of15.7 (SD 9.3) on the FRSS compared with 1.7 (SD1.9) in the control group (Mann±WhitneyÙ' � 45.5, p5 0.0001). A similar ®nding emergedin the TIA group, whose mean score of 10.1 (SD8.7) was also higher than that of the control group(Mann±Whitney Ù' � 141.0, p5 0.001). If fron-tal release signs were judged as present or absentfor each interviewee, the stroke group showed ahigher frequency for each release sign than controls(Table 1). The TIA group had a higher frequencyof all release signs except paratonia, glabellar andsnout re¯exes compared to controls (Table 1).

The combined CVD group (N � 50) was dividedaccording to whether interviewees scored below orabove the median value (12.5) on the FRSS, usingthis dichotomous variable to explore its relation-ship with other variables. Univariate analyses forsociodemographic, physical, neuropsychologicaland mood-related variables are shown in Table 2.

The only predictors of score on the FrontalRelease Signs Scale were verbal ¯uency andDSM-IV depression (Table 3). People classi®ed asdepressed and those generating fewer than 12 words



Table 1. Number of people with primitive re¯exes by group

Stroke TIA Controls

Foot grasp re¯ex 9/25 (36)*** 8/25 (24)**** 0/25 (0)

Hand grasp re¯ex 9/25 (36){ 13/25 (52)*** 1/25 (4)

Glabellar (blink) re¯ex 20/25 (80)* 13/25 (52) NS 7/25 (28)

Palmomental re¯ex 9/25 (36)*** 7/25 (28){ 0/25 (0)

Paratonia 9/25 (36){ 3/25 (12) NS 1/25 (4)

Rooting re¯ex 15/25 (60)* 10/25 (40){ 1/25 (4)

Snout re¯ex 16/25 (64)** 8/25 (24) NS 3/25 (12)

Tactile sucking re¯ex 10/25 (40)***** 8/25 (24){ 1/25 (4)

Visual sucking re¯ex 11/25 (44)***** 8/25 (24){ 1/25 (4)

Note: Chi-squared between-group di�erences (stroke/TIA vs controls): * p5 0.0001;** p � 0.0001; *** p5 0.0005; **** p5 0.001; ***** p5 0.005; { p5 0.01; { p5 0.05.NS, not signi®cant.

Table 2. Univariate analyses for CVD group with FRSS score (5/5 median value) as categorical independentvalue

Dependent variable Chi-squared value Degrees of freedom p value (chi-squared test)

Age* 0.1 1 0.8

Sex 0.1 1 0.8

Marital status 0.0 1 1.0

Race 0.0 1 1.0

Social class 0.0 1 1.0

Physical illness scale score* 0.0 1 1.0

Handicap scale score* 2.9 1 0.1

Social support scale score* 0.0 1 1.0

Systolic blood pressure* 0.4 1 0.5

Diastolic blood pressure* 0.0 1 1.0

Side of stroke lesion/carotid stenosis 0.4 1 0.5

Behavioural Dyscontrol Scale score* 0.9 1 0.3

Trailmaking A time (s)* 4.0 1 50.05

Trailmaking B (s)* 2.0 1 0.1

Verbal ¯uency (F � A � S) score* 8.1 1 0.005

Dementia (69 or less on CAMCOG) 4.2 1 50.05

HRDS score* 2.1 1 0.2

GDS score* 4.0 1 50.05

DSM-IV depressive disorder 3.9 1 50.05

History of depression 0.2 1 0.7

Suicidal thinking 7.3 1 50.001{

*Median values.{Not entered into regression equation, owing to small numbers.

Table 3. Logistic regression analysis for FRSS. Variables entered (in descending order of p value): verbal ¯uency(F � A � S), dementia, GDS score, trail A time, DSM-IV depression, handicap scale score, trail B time

Variable B Standard error

(B)

p value Exp(B)

(odds ratio)

95% con®dence

intervals

Score of 512.5* words (F � A � S) in 1 min ÿ1.91 0.63 0.001 0.15 0.04±0.52

DSM-IV depression 1.75 0.74 0.01 5.74 1.34±24.50

*Median value.



per minute were less likely to show a higher (thanthe median) FRSS score.

DISCUSSION

The vast majority of studies assessing the presenceof primitive re¯exes have examined them in peoplewith Alzheimer's disease. In these studies, thepresence of two of the commonest re¯exes (snout/palmomental) varies from less than 10% (Burnset al., 1990) to over 60% (Basavaraju et al., 1981).However, the prevalence of primitive re¯exes is alsoknown to rise with age (Bakchine et al., 1989). In astudy of non-demented subjects over 65, one ormore of three primitive re¯exes (glabellar, snout orpalmomental) was present in all subjects (Kobaya-shi et al., 1997).

The palmomental re¯ex was the ®rst to appear ina study of 105 cognitively unimpaired subjectsbetween the ages of 40 and 90 (Jacobs andGossman, 1980). A similar study of people withoutdementia aged 50±93 found glabellar and snoutre¯exes to be the commonest primitive re¯exes,present in 29% and 11% of people respectively(Jenkyn et al., 1977). The present study has a verysimilar ®nding, with the two commonest re¯exesbeing glabellar and snout re¯exes, present in 28 and12% of all control subjects respectively.

Primitive re¯exes have been compared betweengroups with Alzheimer's disease and vasculardementia. Two studies found an equal prevalenceof primitive re¯exes in the two dementias (Hoganand Ebly, 1995; Vreeling et al., 1995). In bothstudies, there was no pro®le of re¯exes thatdistinguished between the groups, but one of thestudies found unilateral re¯exes to show a higherprevalence in vascular dementia (Hogan and Ebly,1995). Both studies found an association between ahigher number of primitive re¯exes and greaterseverity of dementia.

In the present study, all nine primitive re¯exeshad a higher prevalence in the stroke group than incontrols. Other studies of patients with cerebro-vascular disease have described similar ®ndings. Ina study of patients with multiple subcorticalinfarcts, snout and grasp re¯exes were present inover 40% of patients and were associated with agreater number of lesions (Corbett et al., 1992).

In the present study, the only re¯exes present inboth stroke and TIA groups and not in controlswere palmomental and foot grasp re¯exes. Theonly study comparing primitive re¯exes in stroke

patients and controls found a combination ofpalmomental and snout re¯exes to di�erentiateolder stroke patients from age-matched controls(Isakov et al., 1984).

The studies so far outlined demonstrate that,although primitive re¯exes may be a marker fororganic brain disease, they are also present inhealthy older adults.

Given the likelihood of organic brain damagefollowing anterior circulation stroke, the ®nding ofa higher mean score on the FRSS in peoplesu�ering a stroke compared with controls maynot be surprising. However, people su�ering TIAalso showed a higher mean score than controls,suggesting a possible aetiopathological role fortransient cerebrovascular ischaemia. It is alsopossible that particular release signs have anassociation with organic brain damage broughtabout by stroke or transient ischaemia. This wouldrequire further exploration involving largernumbers of people with and without cerebro-vascular disease.

It has been suggested that primitive re¯exes havesome prognostic value in the presence of organicbrain disease. Although initial ®ndings suggestedthem to be independent of cognitive state duringthe development of the FRSS (Franssen et al.,1993), the same researcher found a correlation withseverity of cognitive impairment (Franssen andReisberg, 1997). Their presence in Alzheimer'sdisease and vascular dementia also increases therelative risk of mortality (Molsa et al., 1995).

The present study found no association betweenprimitive re¯exes and generalized cognitive impair-ment. Rather, the only neuropsychological variablepredicting the presence of frontal release signs wasverbal ¯uency, a sensitive indicator of frontal lobedamage. Frontal lobe de®cits are known to becommon correlates of stroke (Starkstein et al.,1996); these may be attributable to multiplelacunar (subcortical) infarcts (Rao and Howard,1998).

The other main ®nding from the present studywas that DSM-IV depressive disorder was anindependent predictor of frontal release signs.This appears to be a novel ®nding that has notemerged from other studies. It is already knownthat depressive disorder is associated with abnorm-alities in blood ¯ow to the prefrontal cerebralcortex (Drevets, 1997). In fact, reduced blood ¯owto the left prefrontal cortex (damage to which isassociated with reduced verbal ¯uency) has showna consistent association with depressive disorder



(Bench et al., 1993; Dolan et al., 1994; Drevetset al., 1992). It is also noteworthy that all eightpeople reporting suicidal thinking were in the CVDgroup.

The association between suicidal ideation andcerebrovascular disease has been highlighted in aprevious study of elderly community residents(Rao et al., 1997).

The main methodological problem with thepresent study is the small numbers involved,which may have resulted in type 2 errors whenexamining associations. It is also not known ifpeople with TIA had neurologically silent infarcts,as brain imaging was not carried out in this group.This is particularly important as all patients withTIA had carotid stenosis, which may have resultedin both chronic ischaemic changes and areas of oldinfarction; this would have only become apparent ifbrain imaging had been performed.

The rater was not blind to diagnosis in this study,with the possibility of observer bias in ratingfrontal release signs. The interrater reliability forthe elicitation of frontal release signs is not knownfrom previous studies examining its properties, butrating is operationally de®ned, with each re¯exfurther de®ned according to the strength of theresponse.

It is possible that both controls and stroke/TIApatients may have had accompanying Alzheimer'sdisease. This is probably less likely for the controlgroup, as the selection procedure excluded peoplewho had undergone an operation following a fall,and falls are known to be more common in patientswith Alzheimer's disease (Morris et al., 1987).

None of the patients with either stroke or TIAhad a history ( from either their general practitioneror hospital notes) suggestive of dementia prior tointerview. However, it is possible that more detailedevaluation would have discovered this. This isparticularly important for three main reasons.Firstly, vascular risk factors have been shown ashaving a role in the development of Alzheimer'sdisease (Kokmen et al., 1991). Primitive re¯exes arealso known to occur in Alzheimer's disease; in fact,the study ®rst using the Frontal Release Signs Scaleto di�erentiate cognitively impaired from unim-paired individuals (Franssen et al., 1993) foundparticular re¯exes to be more common in mild andmoderate Alzheimer's disease. Lastly, depressionmay be a harbinger of Alzheimer's disease in laterlife (Greenwald et al., 1997).

Stroke and control patients were interviewedwithin a relatively narrower time interval since the

time of stroke/operation, whereas the TIA groupwere studied at varying time intervals since their®rst TIA. This may have in¯uenced the presence ofprimitive re¯exes in this group. Lastly, it is possiblethat raised systolic/diastolic blood pressure mayhave in¯uenced cognitive function (Rao andHoward, 1998). However, blood pressure showedno association with the FRSS score.

It is perhaps surprising that only two strokepatients were visually impaired given the selectionof people with anterior circulation stroke, but onlyone of these patients was unable to complete thetrailmaking tests as a consequence.

This may have re¯ected the nature of the strokegroup, who were all considered suitable forrehabilitation, which may have been biased againstthose with visual impairment.

There was no association between frontal releasesigns and age or generalized cognitive impairmentin the present study. Given the ®nding that verbal¯uency and depressive disorder were the onlypredictors of frontal release signs in the CVDgroup, it is suggested that primitive re¯exes in thepresence of silent cerebrovascular disease may bemarkers for mood disorder as well as frontal lobepathology. The longitudinal relationship betweenneurological soft signs and mood disorder isworthy of closer attention, particularly in olderpeople with TIA. The incorporation of brainimaging into such studies would also elucidatethis complex interaction.

ACKNOWLEDGEMENTS

Dr Steven Novac (consultant in rehabilitation,Frank Cooksey Unit, Dulwich Hospital) andMr Paul Baskerville (consultant vascular surgeon,

. Primitive re¯exes were more likely to beassociated with symptomatic cerebrovasculardisease

. Depression and verbal ¯uency were the onlyindependent predictors of primitive re¯exes insymptomatic cerebrovascular disease

. TIAs may be associated with silent cerebro-vascular disease, with a possible predilectionfor the frontal lobes

. The incorporation of brain imaging intofuture studies would elucidate the role ofTIAs in the pathogenesis of silent cerebro-vascular disease



King's College Hospital) gave permission to inter-view patients under their care. Dr Sabine Landau,Department of Biostatistics and Computing,Institute of Psychiatry, provided helpful statisticaladvice. The authors would also like to thankMargaret Tomkins, who provided valuablesecretarial assistance in tracing case notes andproviding patient information.

REFERENCES

American Psychiatric Association (1994) Diagnostic andStatistical Manual of Mental Disorders, 4th edn.American Psychiatric Association, Washington, DC.

Bakchine, S., Lacomblez, L., Palisson, E. and Laurent,M. (1989) Relationship between primitive re¯exes,extrapyramidal signs, re¯ective apraxia and severity ofcognitive impairment in dementia of the Alzheimertype. Acta Neurol. Scand. 79, 38±46.

Basavaraju, N. G., Silverstone, F. A., Libow, L. S. andParaskevas, K. (1981) Primitive re¯exes and perceptualsensory tests in the elderlyÐtheir usefulness indementia. J. Chron. Dis. 34, 367±377.

Bench, C. J., Friston, K. J., Brown, R. G. andFrackowiak, R. S. (1993) Regional cerebral blood¯ow in depression measured by positron emissiontomography: The relationship with clinical dimen-sions. Psychol. Med. 23, 579±590.

Benton, A. L. (1968) Di�erential behavioural e�ects offrontal lobe disease. Neuropsychologia 352, 51±60.

Benton, A. L. and Hamsher, K. D. (1989) MultilingualAphasia Examination, 2nd edn. AJA Associates, Iowa.

Blane, D. (1982) Inequality and social class. In Sociologyas Applied to Medicine (D. L. Patrick and G. Scambler,Eds). Balliere Tindall, London.

Brayne, C. and Calloway, P. (1990) The case identi®-cation of dementia in the community: A comparisonof methods. Int. J. Geriatr. Psychiat. 5, 309±316.

Burns, A., Jacoby, R. and Levy, R. (1990) Psychiatricphenomena in Alzheimer's disease. III. Disorders ofmood. Brit. J. Psychiat. 157, 81±86.

Corbett, A. J., Bennett, H. and Kos, S. (1992) Frontalsigns following subcortical infarction. Clin. Exp.Neurol. 29, 161±171.

Dolan, R. J., Bench, C. J., Brown, R. G. and Scott, L. C.(1994) Neuropsychological dysfunction in depression:The relationship to regional cerebral blood ¯ow.Psychol. Med. 24, 849±857.

Drevets, W. C. (1997) Subgenual prefrontal cortexabnormalities in mood disorders. Nature 386,824±827.

Drevets, W. C., Videen, T. O., Price, J. L. and Preskorn,S. H. (1992) A functional anatomical study of unipolardepression. J. Neurosci. 12, 3628±3641.

Folstein, M. F., Folstein, S. E. andMcHugh, P. R. (1975)`Mini Mental State'. A practical method for grad-ing the cognitive state of patients for the clinician.J. Psychiatr. Res. 12, 189±198.

Franssen, E. H. (1991) Cognition-independent neuro-logical symptoms in normal ageing and Alzheimer'sdisease. Arch. Neurol. 48, 148±154.

Franssen, E. H., Kluger, A., Torossian, C. L.and Reisberg, B. (1993) The neurologic syndrome ofsevere Alzheimer's disease. Relationship to functionaldecline. Arch. Neurol. 50, 1029±1039.

Franssen, E. H. and Reisberg, B. (1997) Neurologicmarkers of the progression of Alzheimer's disease. Int.Psychogeriat. 9(Suppl. 1), 297±306.

Fujikawa, T., Yamawaki, S. and Touhouda, Y. (1993)Incidence of silent cerebral infarction in patients withmajor depression. Stroke 24, 1631±1634.

Greenwald, B. S., Kramer-Ginsberg, E. and Bogerts, B.(1997) Qualitative magnetic resonance imaging ®nd-ings in geriatric depression. Possible link betweenlater-onset depression and Alzheimer's disease? Psy-chol. Med. 27, 421±431.

Grigsby, J., Kaye, K. and Robbins, L. J. (1992)Reliabilities, norms and factor structure of theBehavioral Dyscontrol Scale. Percept. Motor Skills74, 883±892.

Hamilton, M. (1960) A rating scale for depression.J. Neurol. Neurosurg. Psychiat. 23, 56±62.

Harwood, R. H., Compertz, P. and Ebrahim, S. (1994)Handicap one year after stroke: Validity of a new scale.J. Neurol. Neurosurg. Psychiat. 57, 825±829.

Hogan, D. B. and Ebly, E. M. (1995) Primitive re¯exesand dementia: Results from the Canadian Study ofHealth and Aging. Age Ageing 24, 375±381.

Isakov, E., Sazbon, L., Coste�, H., Luz, Y. andNajenson, T. (1984) The diagnostic value of threecommon primitive re¯exes. Eur. Neurol. 23, 17±21.

Jacobs, L. and Gossman, M. D. (1980) Three primitivere¯exes in normal adults. Neurology 30, 184±188.

Jenkyn, L. R., Walsh, D. B., Culver, C. M. and Reeves,A. G. (1977) Clinical signs in di�use cerebral dysfunc-tion. J. Neurol. Neurosurg. Psychiat. 40, 956±966.

Kobayashi, S., Okada, K., Koide, H., Bokura, H.and Yamaguchi, S. (1997) Subcortical silent braininfarction as a risk factor for clinical stroke. Stroke 28,1932±1939.

Kokmen, E., Beard, C. M. and Chandra, V. (1991)Clinical risk factors for Alzheimer's disease: Apopulation-based case-control study. Neurology 41,1393±1397.

Livingston, G., Hawkins, A., Graham, N., Blizard, B.and Mann, A. (1990) The Gospel Oak Study:Prevalence rates for dementia, depression and activitylimitation among elderly residents in inner London.Psychol. Med. 20, 137±146.

Molsa, P. K., Marttila, R. J. and Rinne, U. K. (1995)Long-term survival and predictors of mortality in



Alzheimer's disease and multi-infarct dementia. ActaNeurol. Scand. 91, 159±164.

Morris, J. C., Rubin, E. H., Morris, E. J. and Mandel,S. A. (1987) Senile dementia of the Alzheimer's type:An important risk factor for serious falls. J. Gerontol.42, 412±417.

Norusis, M. J. (1990) Statistical Data Analysis. SPSS/PC � 4.0. SPSS, Chicago.

Price, T. R., Manolio, T. A., Kronmal, R. A., Kittner,S. J., Yue, N. C., Robbins, J., Anton-Culver, H. andO'Leary, D. H. (1997) Silent brain infarction onmagnetic resonance imaging and neurological ab-normalities in community-dwelling older adults. TheCardiovascular Health Study. CHS CollaborativeResearch Group. Stroke 28, 1158±1164.

Rao, R., Dening, T. R., Brayne, C. and Huppert, F. A.(1997) Suicidal thinking in community residents overeighty. Int. J. Geriatr. Psychiat. 12, 337±343.

Rao, R. and Howard, R. (1998) Vascular dementia:Dead or alive? Int. J. Geriatr. Psychiat. 13, 277±284.

Reitan, R. (1958) Validity of the trail-making test as anindicator of organic brain disease. Percept. MotorSkills 8, 271±276.

Roth, M., Tym, E., Mountjoy, C. Q., Huppert, F. A.,Hendrie, H., Verma, S. and Goddard, R. (1986)CAMDEX. A standardised instrument for the diag-nosis of mental disorder in the elderly with specialreference to the early detection of dementia. Brit. J.Psychiat. 149, 698±709.

Sheik, J. I. and Yesevage, J. A. (1986) GeriatricDepression Scale (GDS): Recent evidence and devel-opment of a shorter version. Clin. Gerontol. 5,165±173.

Starkstein, S. E., Sabe, L., Vazquez, S., Teson, A.,Petracca, G., Chemerinski, E., Di Lorenzo, G. andLeiguarda, R. (1996) Neuropsychological, psychiatric,and cerebral blood ¯ow ®ndings in vascular dementiaand Alzheimer's disease. Stroke 27, 408±414.

Vreeling, F. W., Houx, P. J., Jolles, J. and Verhey, F. R.(1995) Primitive re¯exes in Alzheimer's disease andvascular dementia. J. Geriatr. Psychiat. Neurol. 8,111±117.

Zito, M., Muscari, A., Marini, E., Di Iorio, A., Puddu,G. M. and Abate, G. (1996) Silent lacunar infarcts inelderly patients with chronic non valvular atrial®brillation. Aging 8, 341±346.



Documents

Primitive reflexes in cerebrovascular disease: a community study of older people with stroke and carotid stenosis