Journal of Affective Disorders 105 (2008) 291–295www.elsevier.com/locate/jad

Brief report

Cognitive and motor features in elderly people with bipolar disorder

Diego J. Martino, Ana Igoa, Eliana Marengo, María Scápola,Ezequiel D. Ais, Sergio A Strejilevich ⁎

Favaloro Foundation, Neurosciences Institute, Bipolar Disorders Program, Congreso 2477 Dto. D, 1428 Ciudad de Buenos Aires, Argentina

Received 27 February 2007; received in revised form 29 April 2007; accepted 15 May 2007Available online 18 June 2007

Abstract

Background: Although elderly people will represent one third of the bipolar population in a few years, data about cognitive andmotor features in these patients are very scarce. The aim of this study was to compare the cognitive and motor functioning betweenelderly euthymic patients with bipolar disorder (BD) and healthy controls, as well as to determine the degree of correlation withpsychosocial functioning.Methods: Euthymic older adults with BD (n=20) and healthy controls (n=20) were evaluated with traditional clinical instrumentsand measures of exposure to psychotropic drugs and extrapyramidal symptoms. All subjects completed an extensiveneuropsychological battery.Results: Patients with BD had more extrapyramidal symptoms and worse performance than healthy controls in psychomotor speed,verbal memory, and executive functions even after controlling sub-clinical symptomatology. These findings were not associatedwith age at onset or length of illness or with current pharmacological exposure. Psychosocial functioning correlated negatively withperformance in psychomotor speed and executive function, and with extrapyramidal symptoms.Limitations: The small sample size and cross-sectional design.Conclusions: Older adult patients with BD in a euthymic state could have a similar cognitive and motor profile to that described inyounger euthymic bipolar patients. Cognitive-motor disturbances may help to explain impairments in daily functioning amongelderly patients with bipolar disorder during remission.© 2007 Elsevier B.V. All rights reserved.

Keywords: Neuropsychology; Old; Executive; Extrapyramidal; Dementia

1. Introduction

Cognitive impairment has been reported in euthymicmixed-age patients with bipolar disorders (BD). Verbalmemory, attention, and executive function impairmentsare the most consistent findings (Robinson et al., 2006).Indeed, it has been suggested that cognitive deficitscould be strong predictors of psychosocial functioning

⁎ Corresponding author. Tel.: +54 11 4833 2424.E-mail address: streji@arnet.com.ar (S.A. Strejilevich).

0165-0327/$ - see front matter © 2007 Elsevier B.V. All rights reserved.doi:10.1016/j.jad.2007.05.014

during remission (Martinez Arán et al., 2004). Addi-tionally, recent studies have shown abnormalities inmotor physiology (Lohr and Caligiuri, 2006), andextrapyramidal and soft neurological symptoms relatedwith executive function and functional outcome in BD(Goswami et al., 2006).

Elderly people will represent one third of the bipolarpopulation in a few years becoming a significant publichealth concern (Sajatovick et al., 2004). Paradoxically,there is a relative lack of knowledge about the cognitiveand motor features of elderly BD patients (Depp and

292 Martino, D.J. et al. / Journal of Affective Disorders 105 (2008) 291–295

Jeste, 2004). Although an increased risk of developingParkinson's disease in patients with major affectivedisorder has been suggested in a epidemiological study(Nilsson et al., 2001), we did not find data addressingmotor functioning in elderly people with BD.

On the other hand, Young et al. (2006) did a reviewabout cognition in BD in old age and found 7 studiesthat concluded that these patients can display cognitiveimpairments. However, just two of those studiesevaluated euthymic patients, and the cognitive testsused provide only an overall assessment of cognitivefunctioning not being useful to characterize the profileof cognitive impairments. Broadhead and Jacoby (1990)studied manic patients who recovered prior to discharge,and found that 25% of the older group scored in thedemented range on the Kendrick Battery Subtests. In amore recent study, nearly half of the BD patients showedone or more standard deviations from the meanregarding healthy controls in Mini-Mental State Exam-ination (MMSE) and in Mattis Dementia Rating Scale,and 17% scored between one and two standarddeviations below the mean of the comparison subjectson the Executive Interview (Gildengers et al.,2004).

The aim of this study is to compare cognitive andmotor features between elderly euthymic patients withBD and healthy controls, as well as to determine thedegree of correlation with psychosocial functioning.Based on previous studies in younger patients, wehypothesize that elderly patients with BD would havehigher cognitive impairments and extrapyramidalsymptoms than healthy controls, and that these featureswould be related with functional outcome.

2. Methods

Twenty outpatients were consecutively selected withthe following inclusion criteria: more than 60 years ofage; diagnosis of BD according to DSM-IV usingStructured Clinical Interview for DSM-IV (First et al.,1996); euthymic [defined by Hamilton DepressionRating Scale (HDRS) (Hamilton, 1960) ≤8 andYoung Mania Rating Scale (YMRS) (Young et al.,1978) ≤6] for at least 4 weeks. Exclusion criteria were:presence of other diagnosis in axis I; antecedent historyof substance abuse; history of mental retardation,neurological disease, or any clinical condition thatcould affect cognitive performance. Additionally, twen-ty healthy controls matched by age and years ofeducation were included: These individuals had nohistory of substance use disorder, neurological orpsychiatric disorders, family history of schizophreniaor bipolar disorder, and they were not taking psycho-

tropic medication. The study was approved by anindependent Ethics Committee and all subjects gavewritten informed consent for their participation afterreceiving a complete description of the study.

2.1. Clinical and psychosocial assessment

All subjects were evaluated with the HDRS, YMRS,MMSE (Folstein et al., 1975), and the UnifiedParkinson's Disease Rating Scale (UPDRS)-III Section(van Hilten et al., 1994) to assess extrapyramidalsymptoms. Psychosocial functioning was assessedwith the General Assessment of Functioning (GAF)(DSM-IV). Current exposition to antidepressants, moodstabilizers, antipsychotics, and benzodiazepines wasassessed by Clinical Scale of Intensity, Frequency, andDuration of Psychopharmacological Treatment (Peraltaand Cuesta, 2002). This scale provides a quantitativemeasure of current exposition to different groups ofpsychotropic medications in a 0–5 point range (0 = nomedication, 1 = sporadic low dose, 2 = continue lowdose; 3 = middle dose, 4 = high dose, and 5 = very highdose). Additional clinical information was obtainedfrom clinical charts and direct patients interview.

2.2. Neuropsychological assessment

Patients and healthy controls completed an extensiveneuropsychological battery selected to assess: 1)estimated premorbid IQ: the WAIS vocabulary subtest(Wechsler, 1955); 2) attention: an analogous ContinuousPerformance Test that includes 60 target stimuli thatalternatively appear in the PC monitor with otherstimuli. When target stimulus appears, subjects have topress the space bar in the keyboard as quickly aspossible. Measures of performance are number of hits,number of false alarms, and latency in milliseconds ofhits. 3) Verbal memory: the Memory Battery of Signoret(Signoret and Whiteley, 1979); 4) psychomotor speed:Simple and Complex Motor Speed. Simple Tappingrequires the subject to tap the space bar of the keyboardwith the dominant and non-dominant index fingers(three trials of 10.5 s with each hand). Complex Tappingrequires the subject to tap the left and right sides of thekeyboard using the two index fingers in alternatingfashion (three trials of 5.5 s). 5) Executive functions:Wisconsin Card Sorting Test (Heaton, 1981).

One experienced psychiatrist (SAS) examined allsubjects. All neuropsychological tests were administeredby other physician (DM) in a quiet testing room accordingto a standardized order. The total procedure was done inan interview of 3–4 h with two breaks to avoid fatigue.

Table 2Results of neuropsychological evaluation of both groups (values areexpressed as mean, standard deviation is shown in brackets)

Bipolarpatients

Healthycontrols

Significance(df=38)

Simple Tapping dominant 24.7 (5.1) 27.5 (3.1) T=−1.9 ⁎Simple Tapping

non-dominant22.5 (5.6) 25.4 (3.5) T=−1.9

Complex Tapping 24.4 (9.0) 31.1 (9.1) T=−2.2 ⁎Immediate recall 5.6 (1.9) 7.4 (1.7) T=−2.9 ⁎⁎Delay recall 5.1 (2.4) 6.9 (2.0) T=−2.4 ⁎Serial learning 8.1 (2.1) 9.0 (1.7) T=−1.3Free delay recall 5.9 (2.3) 7.2 (1.7) T=−1.9 ⁎Recognition 11.4 (1.3) 11.6 (0.5) T=−0.4Attention—hits 57.0 (5.9) 58.9 (2.3) T=−1.3Attention—latency 582 (88) 562 (57) T=0.9Attention—false alarms 6.7 (6.1) 4.0 (3.4) T=1.7WCST—categories 3.4 (2.1) 4.6 (1.7) T=−1.8WCST—total errors 48.4 (22.5) 28.1 (17.8) T=3.1 ⁎⁎

WCST—PerseverativeErrors

26.0 (13.7) 15.5 (8.5) T=2.8 ⁎⁎

WCST: Wisconsin Card Sorting Test.⁎ pb0.05.⁎⁎ pb0.01.

293Martino, D.J. et al. / Journal of Affective Disorders 105 (2008) 291–295

2.3. Data analysis

Independent sample t-test was employed for be-tween-group comparison on continuous variables.Nonparametric variables were compared by usingMann–Withney test or chi-squared test, as appropriate.Partial correlation, as has been suggested by Clark et al.(2002), was used to assess the influence of sub-syndromal mood scores (YMRS and HDRS). Pearsoncorrelation coefficients were calculated to asses therelationship between clinical, neuropsychological, andfunctional variables (in nonparametric variables, resultswere confirmed by Spearman correlation).

3. Results

Patients with BD (20% type I and 80% type II) had amean age at onset of 39.7 (13.0) years, duration of illnessof 28.0 (17.2) years, and 0.94 (1.9) admissions. Bipolarpatients and healthy controls did not differ in gender (75vs. 66% female), age (66.6±8.2 vs. 70.5±9.1), years ofeducation (11.1±4.0 vs. 11.7±3.7), estimated premorbidIQ (T-Score: 51.7±6.6 vs. 55.3±4.4), MMSE (28.3±0.9vs. 28.6±1.6), YMRS (1.7±2.1 vs. 0.7±0.9), and HDRS(2.5±3.0 vs. 2.5±2.2). Subjects with BD had higherprevalence of extrapyramidal symptoms (50 vs. 15%,X2=5.3, pb0.05), higher scores in UPDRS (2.1±2.6 vs.0.4±0.9; Z=2.2, pb0.05), and lower GAF scores (73.6±10.2 vs. 87.5±5.0; T=−5.3 df=25.9 pb0.001) thannormal controls. All patients were receivingmedication attime of testing (Table 1); current exposure assessed withIFD scale to benzodiazepines was 2.1±1.1; to antide-pressants was 1.5±1.4; to mood stabilizers was 2.2±1.2;and to antipsychotics was 1.1±1.2. Results of neuropsy-chological evaluation are shown inTable 2; differencesbetween groups remained significant after controllingsub-clinical symptomatology. Psychosocial functioningcorrelated with measures of psychomotor speed assessedby tapping test (dominant: R=0.63, pb0.01; non-dominant: R=0.6, pb0.01; complex: R=0.48, pb0.05),

Table 1Current medication status of bipolar patients (values are expressed asmean, standard deviation is shown in brackets)

Medications N (%) Mean dose—mg/daily

Lamotrigine 7 (35) 185 (114)Valproate 5 (25) 1020 (476)Lithium 4 (20) 975 (150)Carbamazepine 3 (15) 600 (200)Quetiapine 5 (25) 115 (108)Olanzapine 1 (5) 5 (0)Clonazepam 8 (40) 0.93 (0.49)Antidepressants 8 (40)

and executive function (WCST—Perseverative Errors:R=−0.54, pb0.05). The only clinical feature associatedwith psychosocial functioning was the presence ofextrapyramidal symptoms assessed with the UPDRS(R=−0.70, pb0.01). Additionally, UPDRS scores wereassociated with all measures of psychomotor speed(dominant: R=−0.71, pb0.01; non-dominant: R=−0.71, pb0.01; complex:R=−0.66, pb0.01), and almostwith a measure of executive function (WCST—Persev-erative Errors: R=0.45, p=0.056). No association wasfound between exposure to psychotropic drugs and anyclinical or cognitive variables.

4. Discussion

Our results support data by Young et al. (2006) aboutcognitive impairments in BD in old age and extend themto patients with stringent criteria for euthymia. We foundthat euthymic elderly patients with BD had lowerperformance than healthy controls in measures of verbalmemory, psychomotor speed, and executive functions.These findings in a sample with more than 25 years oflength of illness closely reproduce the cognitive profileshown in previous studies in younger euthymic patients(Robinson et al., 2006), and provide indirect support forthe notion that cognitive impairment may not be moreextensive in elderly BD patients. Similar to findings byGildengers et al. (2004), cognitive impairments were notrelated to chronicity measures such as age at onset,length of illness, or number of admissions.

294 Martino, D.J. et al. / Journal of Affective Disorders 105 (2008) 291–295

The other main result of this study was that elderlyeuthymic patients with BD had higher prevalence ofextrapyramidal symptoms than healthy controls. Thisfinding could be influenced by pharmacological factorsbut quetiapine, given to 5 of 6 patients on antipsychotics,is free or virtually of extrapyramidal effects at such lowdoses (mean 115 mg), and UPDRS scores were notassociated with current exposure to any psychotropicdrug assessed with the IFD. Additionally, UPDRS scoreswere negatively correlated with psychomotor speed andalmost with executive functions. A recent study in youngeuthymic BD patients reported a similar prevalence ofextrapyramidal symptoms (54%), which correlated withlower executive function performance (Goswami et al.,2006). Taken together, these data suggest that regardlessof age, a sub-group of BD patients could presentextrapyramidal symptoms associated with more severecognitive impairment. These findings are particularlyimpressive, as most patients of our study are BD type II.

Finally, psychosocial functioning was associated withpsychomotor speed and executive functions performanceas well as with extrapyramidal symptoms more than withsub-clinical symptoms or chronicity illness measures.These findings suggest that cognitive-motor disturbancesmay help to explain the impairments in daily functioningamong elderly patients with bipolar disorder duringremission, and could have clinical implications if theywill confirm in further studies. First, the routineassessment of these features would be useful in clinicalpractice. Second, these patients may benefit fromneuropsychological rehabilitation and from caution inthe use of drugs that can increase extrapyramidalsymptoms in order to minimize the effect of cognitiveand motor disturbances in their overall functioning.

Some limitations of our study should be taken intoaccount. First and similar to previous studies in euthymicelderly patients, the small size of our sample could limitthe generalizability of the results. Second, we did notdistinguish between elderly patients with early and lateonset BD, although they could be different in cognitiveand neurological features and further studies are neededto enlighten this issue. Finally, the cross-sectional designdoes not allow exploring static or progressive nature ofcognitive impairments and extrapyramidal symptoms.

In summary, euthymic older adults with BD couldhave a cognitive and motor profile characterized byimpairments in verbal memory, psychomotor speed andexecutive functions, as well as extrapyramidal symptoms.Cognitive impairments and extrapyramidal symptomscould be a component of disability in daily functioningamong these patients. Further studies are needed toimprove our understanding and management of cognitive

and motor dysfunction among people with elderly BD.The challenge of obtaining an adequate sample size for theolder bipolar group invites a multi-centre approach to thestudy of this population.

Acknowledgement

The authors would like to thank Kenneth I. Shulman,M.D.

References

Broadhead, J., Jacoby, R., 1990. Mania in old age: a first prospectivestudy. Int. J. Geriatr. Psychiatry 5, 515–522.

Clark, L., Iversen, S., Goodwin, G., 2002. Sustained attention deficit inbipolar disorder. Br. J. Psychiatry 180, 313–319.

Depp, C., Jeste, D., 2004. Bipolar disorder in older adults: a criticalreview. Bipolar Disord. 6, 343–367.

First, M., Spitzer, R., Gibbon, M., Williams, J., 1996. StructuredClinical Interview for DSM-IVAxis I Disorders—Clinical Version(SCID-CV). American Psychiatry Press, Washington, DC.

Folstein, M., Folstein, S., McHugh, P., 1975. “Mini-Mental State“: apractical method for grading the cognitive state of patients for theclinician. J. Psychiatry Res. 12, 189–198.

Gildengers, A., Butters, M., Seligman, A., McShea, M., Miller, M.,Mulsant, B., Kupfer, D., Reynolds, Ch., 2004. Cognitive functioningin late-life bipolar disorder. Am. J. Psychiatry 161, 736–738.

Goswami, U., Sharma, A., Khastigir, U., Ferrier, N., Young, A.,Gallagher, P., Thompson, J., Moore, P., 2006. Neuropsychologicaldysfunction, soft neurological signs and social disability in euthymicpatients with bipolar disorder. Br. J. Psychiatry 188, 366–373.

Hamilton, M., 1960. A rating scale for depression. J. Neurol NeurosurgPsychiatry 23, 56–62.

Heaton, R., 1981. Wisconsin Card Sorting Test. PsychologicalAssesment Resources, Odessa, FL.

Lohr, J., Caligiuri, M., 2006. Abnormalities in motor physiology inbipolar disorder. J Neuropsychiatr. Clin. Neurosci. 8 (3), 342–349.

Martinez-Arán, A., Vieta, E., Reinares, M., Colom, F., Torrent, C.,Sanchez-Moreno, J., Benabarre, A., Goikolea, J., Comes, M.,Salamero, M., 2004. Cognitive function across manic orhippomanic, depressed, and euthymic states in bipolar disorder.Am. J. Psychiatry 161, 262–270.

Nilsson, F., Kessing, L., Bolwig, T., 2001. Increased risk of developingParkinson's disease for patients with major affective disorder: aregister study. Acta Psychiatr. Scand. 104 (5), 380–386.

Peralta, V., Cuesta, M., 2002. Escala Clínica de Intensidad, Frecuenciay Duración del Tratamiento Psicofarmacológico (Escala IFD).Virgen del Camino Hospital, Pamplona, Spain.

Robinson, L., Thompson, J., Gallagher, P., Goswami, U., Young, A.,Ferrier, N., Moore, B., 2006. A meta-analysis of cognitive deficitsin euthymic patients with bipolar disorder. J. Affect. Disord. 93,105–115.

Sajatovic, M., Blow, F., Ignacio, R., 2004. Age-related modifiers ofclinical presentation and health service use among veterans withbipolar disorder. Psychiatr. Serv. 2004 (55), 1014–1021.

Signoret, J., Whiteley, A., 1979. A memory battery scale. Int.Neuropsychol., Soc. Bull 2, 2–26.

van Hilten, J., van der Zwan, A., Zwinderman, A., Ross, R., 1994.Rating impairment and disability in Parkinson's Disease RatingScale. Mov. Disord. 9, 84–88.

295Martino, D.J. et al. / Journal of Affective Disorders 105 (2008) 291–295

Wechsler, D., 1955. Wechsler Adult Intelligence Scale—Revised.Psychological Corporation, Cleveland.

Young, R., Biggs, J., Ziegler, V., Meyer, D., 1978. A rating scale formania: reliability, validity and sensitivity. Br. J. Psychiatric. 133,429–435.

Young, R., Murphy, C., Heo, M., Schulberg, H., Alexopoulos, G.,2006. Cognitive impairments in bipolar disorder in old age:Literature review and findings in manic patients. J. Affect. Disord.92, 125–131.