© 2014 John Wiley & Sons A/S Published by John Wiley & Sons Ltd.

Bipolar Disorders 2014: 16: 326–336

BIPOLAR DISORDERS

Brief Report

Using the Brief Assessment of Cognition in Schizophrenia (BACS) to assess cognitive impairment in older patients with schizophrenia and bipolar disorder Cholet J, Sauvaget A, Vanelle J-M, Hommet C, Mondon K, Mamet J-P, Camus V. Using the Brief Assessment of Cognition in Schizophrenia (BACS) to assess cognitive impairment in older patients with schizophrenia and bipolar disorder. Bipolar Disord 2014: 16: 326–336. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives: A growing body of evidence suggests that impairment in cognitive functioning is an important clinical feature of both schizophrenia and bipolar disorder, and that these cognitive alterations worsen with age. Although cognitive assessments are increasingly becoming a part of research and clinical practice in schizophrenia, a standardized and easily administered test battery for elderly patients with bipolar disorder is still lacking. The Brief Assessment of Cognition in Schizophrenia (BACS) captures those domains of cognition that are the most severely affected in patients with schizophrenia and the most strongly correlated with functional outcome. The primary aim of our study was to investigate the clinical usefulness of the BACS in assessing cognitive functioning in elderly euthymic patients with bipolar disorder, and to compare their cognitive profile to that of elderly patients with schizophrenia. Methods: Elderly euthymic patients with bipolar disorder or schizophrenia were assessed using the BACS and a standard cognitive test battery. Results: Fifty-seven elderly patients (aged 60 years and older) with bipolar disorder (n = 42) or schizophrenia (n = 15) were invited to participate. All of the patients were assessed by the BACS as being cognitively impaired. The patients with bipolar disorder scored significantly higher on the global scale and the verbal memory and attention sub-scores of the BACS than the patients with schizophrenia. Discussion: The BACS appears to be a feasible and informative cognitive assessment tool for elderly patients with bipolar disorder. We believe that these preliminary results merit further investigation.

Bipolar disorder (BD) affects more than 1% of the general population and is the sixth leading cause of disability in developed countries (1, 2). Recent data suggest that functional impairment in patients with BD is remarkably prevalent, particularly with regard to independent living, social relationships, and vocational success (3, 4). Nearly 25% of patients with BD end up going into nursing homes,

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Jennyfer Choleta, Anne Sauvageta, Jean-Marie Vanellea, Caroline Hommetb, Karl Mondonb, Jean-Philippe Mametc and Vincent Camusb a Po^le Universitaire d’Addictologie et de Psychiatrie, CHU de Nantes, Universite de Nantes, Nantes, bCHRU de Tours, Universite Francß ois Rabelais de Tours, INSERM U930, Tours, cNeuilly sur Seine, France

doi: 10.1111/bdi.12171 Key words: aging – assessment tool – BACS – bipolar disorder – cognitive impairment Received 26 September 2012, revised and accepted for publication 28 July 2013 Corresponding author: Dr. Jennyfer Cholet Po^le Universitaire d’Addictologie et de Psychiatrie Ho^pital Saint Jacques 85 rue Saint Jacques Nantes Cedex 1 44093 France Fax: 0033-2-40-84-61-18 E-mail: [email protected]

and 7.2% are hospitalized in long-term psychiatric care facilities (5). Cognitive impairment has been documented in BD, psychotic mood disorders (6–9), and schizophrenia (SCZ) (10), and is associated with worse functional outcomes. Recent meta-analyses have confirmed that cognitive impairment exists across all bipolar mood states, including euthymia (11–

Using the BACS in older patients with BD 15). Several studies reported that neurocognitive impairments in BD persist during remission, and concerned mainly sustained attention (16), verbal memory (17), and executive functions (7). A recent meta-analysis (18) defined the cognitive endophenotypes of euthymic patients with BD as impairment in executive functions, especially flexibility and inhibition, verbal memory, and sustained attention. These recent data suggest that patients with BD and patients with SCZ share common features concerning cognition, including executive functions, verbal memory, and perceptual and motor functions (19–22). With increasing age, the differences in cognitive functioning between BD and SCZ seem more quantitative than qualitative, and patients with BD suffer from fewer cognitive disorders than patients with SCZ (11, 12, 23). According to Gildengers and colleagues (12), over 50% of elderly patients with BD have documented cognitive impairment. Furthermore, the evolution of global cognitive aging in patients with BD may lead to a specific form of dementia (24, 25) that is independent of the incidence of neurodegenerative disorders such as Alzheimer’s disease. Thus, better assessments of cognitive functioning must be developed to allow better detection of cognitive impairment and to limit diagnostic errors. Many confounding factors (26, 27) may contribute to a worsening of cognitive performance, including age, the patient’s comorbid environment, the severity of BD, an early onset (before age 18 years) (28, 29), the polarity of the thymic stage (30), the number of manic episodes (31), the number of suicide attempts (32), a history of psychosis, residual symptoms (especially depression), and associated comorbidities, such as addictive disorders (33–35), anxiety disorders, and cardiovascular disorders (36–38). The possible toxicity of specific treatments for BD (39–41) must also be considered. Although the assessment of cognition is increasingly becoming an integral part of research and clinical practice in SCZ, there is no standardized and easily administered test battery for elderly patients with BD. Although several scales have been developed, they are limited by their low sensitivity and specificity (42–44). However, the International Society for Bipolar Disorders (ISBD) Cognition Committee has evaluated the suitability of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for use in BD, and proposed a preliminary cognitive battery that could be used internationally in research on BD (45). They

posit that the following four functions should be evaluated in patients with BD using five of the ten subtests of the MCCB: (i) psychomotor speed, with Symbol Coding; (ii) executive functions with the Trail Making Test (TMT)–part B (TMT-B) and the Verbal Fluency Tests (semantic and alphabetical); (iii) attention with the TMT– part A (TMT-A); and (iv) visual learning with the Brief Visuospatial Memory Test-Revised and the Rey Osterrieth Complex Figure. They also advocate further exploration of working memory and verbal memory. Furthermore, they suggest incorporating inhibition tests such as the Hayling Sentence Completion Test (HSCT) and tests of strategy and planning such as the Tower of London Test. The Brief Assessment of Cognition in Schizophrenia (BACS) (46) meets the requirements set out by the ISBD Cognition Committee. The tests that they selected assess the cognitive domains that are most severely impaired in SCZ and the most strongly correlated with functional outcome, particularly verbal memory using the List Learning Task (number of words recalled per trial), working memory using the Digit Sequencing Task (number of correct responses), executive functions using the Verbal Fluency Test, involving the use of category instances and the controlled oral word association test (number of words generated per trial) and Tower of London test (number of correct responses), attention using Symbol Coding Test (number of correct numerals), and motor speed using the Token Motor Task (number of tokens correctly placed into the container). The BACS is simple to use, requiring only paper, pencils, and a stopwatch. It can also be administered by different caregivers and takes approximately 35 min to complete. This test battery was originally validated on a sample of 150 patients with SCZ and compared to a sample of 50 controls matched for age, parental education, and ethnic group. A standard test battery was used as a reference to evaluate concurrent validity. At the end of these validation procedures, the BACS presented satisfactory psychometric properties with a good completion rate and good test–retest reliability. Its sensitivity was comparable to that of a battery of tests requiring two hours or more to complete. Furthermore, the global score on the BACS was highly correlated with the global score on the standard battery for patients and controls alike. After accounting for age, gender accounted for only 2% of the variance in the composite scores. Moreover, it did not affect test–retest reliability and was consistent when

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Cholet et al. repeated within the same patient. Perhaps more important, the cognitive deficits measured by the BACS are clinically relevant, as they are correlated with patient variables related to living independently and to functional capacity (47). Its values were normalized in 2008, by the same team, in patients up to 79 years of age (48). A French version of the BACS was validated in 2007 (49). We hypothesized that the BACS would meet the requirements of the ISBD Cognition Committee and could be used in elderly euthymic patients with BD. To test this hypothesis, the results obtained using the BACS were compared to those obtained by a standard cognitive test battery. Moreover, the BACS must be sensitive to confounding variables encountered in the study of BD (e.g., the type of BD, its severity, comorbidities, and types of treatment). We also expected to find a correlation between the scores on the BACS and the level of psychosocial functioning. Finally, a high sensitivity to the specific psychiatric diagnosis (BD versus SCZ) was deemed to be useful.

Materials and methods Study design

For this cross-sectional study, patients with BD or SCZ were recruited by their psychiatrists from psychiatric hospitals and psychiatric wards in the area of Nantes and Tours (France). They were not matched for age or gender. The patients underwent two rounds of interviews, each lasting two hours, within a maximum period of two weeks. Each patient provided written informed consent prior to participation. Inclusion criteria

To be included in the study, the patients were required to be at least 60 years of age. The patients had to meet the DSM-IV-TR diagnostic criteria (50) for either BD type I or II or SCZ. The diagnosis was confirmed by the Mini International Neuropsychiatric Interview (MINI)-version 5.0.0 (51). The patients also had to be euthymic and have scores below 15 on the Montgomery– Asberg Depression Rating Scale (MADRS) (52), below nine on the Hamilton Depression Rating Scale (HDRS) (53), below 15 on the Bech–Rafaelson Mania Scale (MAS) (54), and below 20 on the Young Mania Rating Scale (YMRS) (55). The patients also had to have a composite score on the Positive and Negative Syndrome Scale (PANSS) below 15 or above +11 (56).

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Exclusion criteria

Subjects whose native language was not French were not included in the study. Patients with schizoaffective disorders were not included. Any disease that may have affected cognitive functions (e.g., stroke, epilepsy, neurodegenerative diseases, Parkinson’s disease, brain metastases, unbalanced metabolic or endocrine diseases, and uncontrolled arterial blood pressure) was considered grounds for exclusion. A delay of less than 20 weeks between the completion of the tests and the last session of electroconvulsive therapy (ECT) was also a criterion for exclusion. Dependence on a psychoactive substance, excluding tobacco, in the last six months and acute intoxication due to psychoactive substance use in the month preceding the completion of the cognitive assessment also constituted reasons for exclusion. Cognitive assessment

Each patient completed the BACS and a standard cognitive test battery, including the Mini Mental State Examination (MMSE) (57), the Mattis Dementia Rating Scale (DRS) (58), the Clock Drawing Test (CDT) (59), the Hayling Sentence Completion Test (HSCT) (60), the TMT–A and TMT–B (61), and the Rey Complex Figure Test (RCFT) (copy and recall) (62). French normative data for the DRS are lacking but a score was considered pathological if it was below 141 (63). Psychosocial functioning

Functional outcomes were evaluated by the following assessment tools: Activities of Daily Living (ADL) (64), Instrumental Activities of Daily Living (I-ADL) (65), Social Activities of Daily Living (S-ADL) (66), and Global Assessment of Functioning (GAF) scale (67). Additional data

We collected sociodemographic data on age, gender, educational level, number of years worked, and number of years spent living in institutions (foster homes, retirement homes, and long-term psychiatric hospitalizations). We estimated the severity of BD based on the type of BD, the age of onset, which corresponded to the first contact with psychiatric services (consultation or hospitalization), the number of hospitalizations, the total time spent in hospitals, and the history of ECT or lithium therapy. The presence and type of somatic and psychiatric comorbidities were also recorded.

Using the BACS in older patients with BD Statistical analysis

Scores on the TMT-A and TMT-B were standardized, using the conversion table of Poitrenaud and colleagues (68). BACS total and sub-scale scores were transformed and adjusted for age using published normative data (48). Adjusting for age enabled us to investigate the specific roles of BD and comorbidities that may accelerate cognitive decline beyond the effects of normal aging. We analyzed the data using SAS/STAT (SASâ software, SAS version 9.2; SAS Institute, Cary, NC, USA). Due to the exploratory nature of our pilot study and our sample size, our objective was to evaluate the feasibility of using the BACS in elderly patients with BD using non-parametric tests and univariate analyses; our aim was neither to test the validity of the BACS per se nor to evaluate its internal consistency. The means were compared using the Wilcoxon test. Differences were considered statistically significant at p < 0.05. Spearman’s rank correlation coefficient (R), adjusted on Fisher’s exact test, was used to evaluate the association between the scores obtained on the BACS and the standard cognitive test battery and between the scores obtained on the BACS and the results obtained on the functional scales. Hypothesis tests were considered statistically significant for a correlation coefficient (R) greater than 0.3 associated with p < 0.05. This protocol was approved by the Ethics Committee of Tours (France).

45.2% had a late-onset form of BD (diagnosed after the age of 45). BD type I predominated (64.3%). Less than 20% of the patients with BD were currently, or had previously been, institutionalized. Moreover, 28.6% of the patients with BD belonged to a high polyvascular risk category. Additionally, 23.8% of the patients had an associated anxiety disorder and 4.8% had a history of psychoactive substance use. Half of the patients with BD had a history of lithium therapy. The mean age of the patients (ten females) with SCZ was 68.8 years. In this cohort, 14.3% had early-onset SCZ and 14.3% had late-onset SCZ. Forty percent were currently, or had previously been, institutionalized. One-third of the patients with SCZ were in a high polyvascular risk category and three of the patients (20%) had an associated anxiety disorder. None of the patients suffered from a substance use disorder, not including tobacco use. Tables 1 and 2 present the demographic and psychosocial data for the BD and SCZ groups, respectively. The results, in both groups, from the standard cognitive test battery are shown in Table 3, and from the BACS in Table 4. As the correlations between the BACS and the demographic data, the psychosocial data, and the standard cognitive battery are well known for patients with SCZ, we studied the correlations with the BACS for the BD group alone.

Results

Correlations between the BACS and the demographic and psychosocial data for patients with BD

All of the 42 patients with BD and 15 patients with SCZ completed the full battery of cognitive assessments. The mean age of the patients with BD (28 females) was 70.2 years, and the vast majority (n = 38) were younger than 80 years of age. Of the patients with BD, 9.5% had early-onset BD and

Age was correlated positively with the overall score on the BACS and its List Learning, Verbal Fluency, particularly the categorical fluency, and the Symbol Coding Test sub-scores. This correlation was no longer statistically significant when we used the adjusted-for-age scores (Z-scores) on the BACS.

Table 1. Demographic data for patients with bipolar disorder and schizophrenia Bipolar disorder Age, years, mean (SD) Age at onset, years, mean (SD) Hospitalizations, mean (SD) Total number Time spent, days Educational level, years, mean (SD) Duration of employment, years, mean (SD) Treatment by ECT, % Duration of lithium therapy, years, mean (SD) History of suicide attempt, % No. of suicide attempts, mean (SD)

Schizophrenia

70.2 (7.2) 41.2 (17.6) 11.0 (12.9) 651.6 (1,103.7) 8.8 (3.8) 26.3 (14.8) 26.2 8.2 (12.4) 50 1.0 (1.2)

p-value

68.8 (7.4) 28.4 (11.4)

NS < 0.05

15.8 (16.1) 2,143.9 (3,454.5) 7.9 (4.7) 14.4 (12.4) 6.7 0 20 0.3 (0.6)

NS 0.10 < NS 0.10 < NS < 0.01 0.10 < 0.10
0.10); SD = standard deviation.

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Cholet et al. Table 2. Psychosocial data for patients with bipolar disorder and schizophrenia Bipolar disorder Measures

Average

HDRS MADRS MAS YMRS PANSS: composite score GAF ADL I-ADL S-ADL

3.9 4.1 1.7 3.5 2.0 65.2 6.6 15.6 9.8

Schizophrenia

Range

SD

0–8 0–13 0–5 0–11 12 to +10 30–90 6–11 9–36 6–19

Average

2.4 3.4 1.8 3.0 4.7 17.1 1.3 6.3 4.0

Range

4.9 2.5 1.1 2.7 1.3 45.1 7.4 23.3 13.8

1–8 0–7 0–5 0–8 10 to +6 21–70 6–11 9–35 6–22

SD

p-value

2.0 2.1 1.5 2.9 4.5 18.0 1.8 8.6 5.4

NS NS NS NS NS < 0.01 NS < 0.01 < 0.05

ADL = Activities of Daily Living; GAF = Global Assessment of Functioning Scale; HDRS = Hamilton Depression Rating Scale; I-ADL = Instrumental Activities of Daily Living; MADRS = Montgomery– Asberg Depression Rating Scale; MAS = Bech–Rafaelson Mania Scale; NS = non-significant (p > 0.10); PANSS = Positive and Negative Syndrome Scale; S-ADL = Social Activities of Daily Living; SD = standard deviation; YMRS = Young Mania Rating Scale.

Table 3. Results of the standard cognitive test battery for patients with bipolar disorder and schizophrenia Bipolar disorder Measures MMSE TMT–A, standardized score TMT–B, standardized score Clock Drawing Test, standardized score HSCT First part: time, sec Inhibition: errors, number Dementia Rating Scale Global score Attention Initiation Construction Concept Memory Rey Complex Figure Test Copy: score Recall: score Copy: time, sec

Average

Range

Schizophrenia SD

Average

Range

SD

p-value

26.0 4.5 3.6 25.8

30–18 1–8 1–10 10–33

3.1 2.3 2.5 8.3

23.8 3.3 2.3 21.9

11–29 1–7 0–7 0–34

4.8 2.1 2.1 10.8

NS 0.10 < p < 0.05 0.10 < p < 0.05 NS

58.1 4.4

44–98 0–15

12.7 4.6

72.2 8.3

51–112 0–15

18.3 5.2

< 0.01 < 0.01

126.6 35.4 31.0 5.8 33.2 21.2

88–144 31–37 14–37 3–6 19–39 13–25

12.5 1.2 6.7 0.6 4.6 2.7

111.9 33.6 26.2 4.5 29.7 17.93

68–142 25–37 11–37 0–6 15–38 6–25

23.1 3.6 8.0 2.3 7.6 4.9

< 0.05 NS 0.10 < p < 0.05 < 0.05 NS < 0.01

28.7 9.9 346.9

11–38 4–24 43–1,650

6.1 6.0 286.1

22.5 8.4 298.9

1–36 0–20 115–922

13.2 6.3 208.4

NS NS NS

HSCT = Hayling Sentence Completion Test; MMSE = Mini Mental State Examination; NS = non-significant (p > 0.10); SD = standard deviation; TMT–A = Trail Making Test–part A; TMT–B = Trail Making Test–part B.

The overall BACS score was significantly correlated with the level of education, regardless of age (R = 0.48, p = 0.004). Sub-scores of List Learning (R = 0.34, p = 0.04), the Digit Sequencing Task (R = 0.39, p = 0.02), Verbal Fluency (R = 0.46, p = 0.007), and Symbol Coding Test (R = 0.53, p = 0.002) were also correlated with the educational level when age was included as a confounder. The Tower of London test scores were not correlated with the level of education. The type of BD was not correlated with any of the cognitive data. Earlier onset was negatively correlated with the Z-scores for the Token Motor

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Task (R = 0.48, p = 0.004) and the Tower of London test (R = 0.37, p = 0.03). Correlations between the BACS and the standard cognitive battery test for patients with BD

The global score on the BACS was positively correlated with all the results from the standard battery tests (Table 5). The List Learning Z-scores, in particular, were strongly correlated with the memory sub-scores of the DRS. The Digit Sequencing Task sub-scores were highly correlated with the TMT–B, the conceptual sub-score of the DRS, and

Using the BACS in older patients with BD Table 4. Results of the Brief Assessment of Cognition in Schizophrenia (BACS) for patients with bipolar disorder and schizophrenia Bipolar disorder Measures BACS Global score List Learning Digit Sequencing Task Token Motor Task Verbal Fluency Semantic Alphabetical Symbol Coding Tower of London Test BACS, Z-scores Global score List Learning Digit Sequencing Task Token Motor Task Verbal Fluency Symbol Coding Tower of London Test

Schizophrenia

Average

Range

SD

160.6 29.8 13.9 45.0 34.3 17.6 16.8 25.5 12.2

80–275 5–60 7–27 10–74 11–69 7–31 5–39 2–60 5–19

2.0 1.2 1.4 1.1 1.0 2.3 0.8

Average

Range

SD

p-value

50.6 10.9 5.2 14.1 14.1 6.7 8.4 13.8 3.4

127.7 22.7 13.1 34.6 28.5 14.1 14.5 19.5 9.2

28–222 8–44 4–25 4–56 6–49 4–23 2–31 1–55 1–19

57.1 10.1 6.3 15.8 14.3 6.7 9.1 15.8 5.8

0.10 < p < 0.05 < 0.05 NS < 0.05 NS NS NS NS 0.10 < p < 0.05

1.5 1.1 1.3 0.9 1.1 1.5 0.9

3.0 2.0 1.6 1.9 1.4 2.9 1.6

1.8 1.0 1.6 1.0 1.1 1.7 1.5

0.10 < p < 0.05 < 0.05 NS < 0.05 NS NS NS

5.1 to +1.1 4.1 to +1.5 4.3 to +1.7 2.6 to +0.9 2.9 to +1.4 4.9 to +1.1 2.8 to +1.0

0.2 to 5.9 3.6 to 0 4.0 to +1.2 3.6 to +0.1 3.4 to +0.2 5.3 to +0.5 3.6 to +0.8

NS = non-significant (p > 0.10); SD = standard deviation.

the inhibition part of the HSCT. The Token Motor Task Z-scores were correlated with the TMT-A. The sub-scores of the Symbol Coding Test were positively correlated with all the other results. The alphabetical Verbal Fluency Z-score was strongly positively correlated with the TMT–B, the inhibition part of the HSCT, and the CDT. Conversely, the semantic Verbal Fluency Z-score was correlated with the sub-scores of initiation and concepts in the DRS, the TMT-B, and the RCFT. The subscores of the Tower of London test were correlated with all the other results, particularly with the TMT–B, the global score of the DRS, and the initiation sub-score of the DRS. Correlations with therapeutic history data for patients with BD

Hospitalizations. All of the BACS Z-scores (R = 0.63 to 0.38; p = 0.0002, p = 0.03), except for Verbal Fluency (including categorical fluency and alphabetical fluency), were negatively correlated with the number of hospitalizations. The total duration of hospitalizations was negatively correlated with all the sub-scores of the BACS (R = 0.66 to 0.38; p ≤ 0.0001 to p = 0.02). Treatments. Patients with BD with a history of lithium therapy were significantly less successful on the Token Motor Task (R = 0.30) than patients without a history of lithium therapy, but the observed difference did not reach statistical significance (p = 0.07). The overall scores on the BACS

for the two subgroups of patients with BD (with and without lithium therapy) were statistically comparable. A history of ECT was not correlated with the MMSE or DRS scores. Although the global score on the BACS was, on average, lower in patients with than in patients without a history of ECT, the difference in this score was not statistically significant (p = 0.09). However, patients with a history of ECT performed significantly lower on the Token Motor Task compared to patients with no history of ECT (p = 0.04). Moreover, patients with no history of ECT were more successful on the Tower of London Test and the test of semantic Verbal Fluency than the patients with a history of ECT, although not to a statistically significant degree (both p = 0.06). Comparison between patients with BD and patients with SCZ

The patients with BD completed the first part of the HSCT more quickly and made fewer errors during the inhibition part compared to patients with SCZ. Patients with BD had higher scores on the DRS than patients with SCZ. Their scores on the TMT–A and TMT–B were significantly higher than those of patients with SCZ. The two groups performed similarly on the RCFT and the MMSE (Table 3). The patients with BD also attained significantly higher global scores on the BACS and List Learning and Token Motor Task sub-

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Cholet et al. scores. Although they also performed better on the Tower of London Test compared to patients with SCZ, this difference did not reach statistical significance when the Z-scores were compared (Table 4). The GAF score was higher among patients with BD, but the I-ADL and S-ADL scores were higher among patients with SCZ (Table 2). Nevertheless, the GAF scores were positively correlated with the Z-scores of the BACS, especially the global score. The ADL scores were negatively correlated with all the Z-scores of the BACS, particularly with Verbal Fluency, but not with the List Learning and the Symbol Coding Test. The I-ADL score and all of the Z-scores of the BACS, except for the Digit Sequencing Task, were negatively correlated. The S-ADL score was negatively correlated with all the Z-scores of the BACS, and strongly negatively correlated with the Tower of London Test (Table 5). Discussion

Our study showed that the cognitive profiles of elderly patients with SCZ and BD differ quantitatively rather than qualitatively. Although we did not include healthy control subjects in our study, the normative data for the BACS (48) allowed us to conclude from our data that the cognitive profile of elderly patients with BD is intermediate between the profiles of patients with SCZ and those of the general population. The global Z-score of the BACS was also higher for the patients with BD ( 1.99 SD) than for those with SCZ. Elderly patients with SCZ had greater impairment in verbal memory and attentional abilities than older patients with BD. These results are consistent with those of recent studies (14, 15, 21, 69–71). Interestingly, the BACS seems to have sufficient sensitivity to differentiate between the cognitive impairment of elderly patients with SCZ and with BD. However, adjusted analyses, in particular on the number of hospitalizations in a larger sample size, are needed to confirm this conclusion. Elderly euthymic patients with BD have cognitive impairment concerning memory, attention, executive function, and speed processing. Our observations cannot be explained by the effects of age alone because the results survive adjustment for age. Moreover, our observations are consistent with those in previous reports in the literature (7, 16–22) and provide further evidence of the existence of cognitive endophenotypes that are common to patients with BD, regardless of their age (1, 7, 16). Of note, correlations between the BACS and the standard screening batteries (MMSE and DRS) were strong and positive, as were correla-

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tions between each sub-score of the BACS and the standardized tests evaluating the same cognitive domains. Thus, our results revealed that the BACS is a useful and promising tool for the assessment of cognitive functioning in elderly patients with BD. Our pilot study did not allow us to distinguish the possible effects of BD type, the age at onset, the iatrogenic effect of lithium, and the cumulative effect of mood episodes and number of hospitalizations (39–41). However, the scores obtained on the BACS were negatively correlated with the severity of bipolar illness (based on an estimate obtained using the age at onset and the number and duration of hospitalizations) and a history of ECT. Our results confirmed those in previous reports describing the detrimental effect of bipolar illness on global cognitive functioning (1, 32–35, 40). Interestingly, the BACS appears to be sensitive enough to detect these manifestations of the illness. Correlations between the BACS global score and scores on the GAF, ADL, I-ADL, and S-ADL provide additional evidence that the BACS global score may be a good indicator of psychosocial functioning of elderly patients with BD. Correlation between BACS and psychosocial functioning scores is consistent with recent data reported in the literature (1, 5, 70, 71) and highlights the deleterious functional impact of the cognitive impairment affecting patients with BD. We found no correlation between BACS scores and any of the thymic scales (MADRS, HDRS). The exclusion of patients who scored highly on these scales may explain this finding as only a few residual depressive symptoms may have been present in the patients who were included in the research. As our study was of an exploratory nature, there were some important limitations. First, the small sample size may have caused the study to be under-powered and restricted us to performing only univariate, nonparametric analyses, as opposed to multivariate statistics. Indeed, the small sample size did not allow us to adjust our analysis to take account of several potential confounding factors such as BD type, the age at onset, and the number of hospitalizations. Moreover, we were not able to explore the effects of somatic and addictive comorbidities, or of treatments received during the course of the patients’ illness. Second, we did not use any randomization between groups. All the patients were referred to us by their respective psychiatrists based on the criteria for inclusion and the predicted ability for the patient to achieve the full battery of tests. Thus, only those patients who were the most interested in participating in the study and the most likely to be

0.78 0.56 0.58

0.58 0.72 0.65 0.72 0.74 0.61

0.71 0.51 0.54

0.48 0.64

0.65 0.58

0.42 0.57 0.59 0.44 0.34 0.45

0.58 0.65 0.53

0.31 0.56

0.34 0.51

TMT–A

0.60 0.58 0.54

MMSE

0.67 0.72

0.58 0.75

0.82 0.69 0.61

0.64 0.71 0.72 0.64 0.75 0.73

0.86 0.71 0.63

TMT–B

0.39 0.59

0.42 0.47

0.55 0.43 0.38

0.47 0.50 0.47 0.46 0.42 0.59

0.56 0.46 0.44

CDT

0.46 0.20

0.35 0.54

0.49 0.47 0.29

0.42 0.64 0.62 0.61 0.57 0.30

0.61 0.51 0.34

0.46 0.54

0.27 0.55

0.62 0.53 0.51

0.37 0.53 0.52 0.53 0.48 0.55

0.58 0.52 0.52

HSCT inhibition

0.69 0.72

0.60 0.76

0.81 0.54 0.55

0.67 0.79 0.78 0.69 0.75 0.73

0.85 0.57 0.59

DRS global score

0.30 0.29

0.26 0.24

0.36 0.04 0.35

0.31 0.27 0.20 0.30 0.36 0.34

0.36 0.13 0.43

DRS attention

0.68 0.66

0.62 0.77

0.75 0.43 0.44

0.64 0.80 0.78 0.68 0.73 0.68

0.82 0.48 0.48

DRS initiation

0.41 0.36

0.22 0.48

0.45 0.45 0.39

0.33 0.49 0.44 0.49 0.47 0.37

0.50 0.43 0.44

DRS construction

0.57 0.52

0.28 0.46

0.53 0.25 0.54

0.43 0.48 0.52 0.42 0.61 0.54

0.56 0.31 0.59

DRS concept

0.35 0.40

0.35 0.61

0.57 0.60 0.43

0.48 0.60 0.51 0.58 0.42 0.36

0.61 0.54 0.46

DRS memory

0.43 0.52

0.50 0.41

0.62 0.56 0.50

0.52 0.47 0.48 0.40 0.50 0.53

0.64 0.56 0.55

RCFT copy score

0.38 0.59

0.52 0.52

0.61 0.67 0.42

0.51 0.55 0.57 0.49 0.39 0.58

0.61 0.66 0.36

RCFT recall score

0.56 0.54

0.47 0.39

0.65 0.53 0.40

0.42 0.44 0.44 0.39 0.53 0.58

0.60 0.54 0.41

GAF

0.25 0.35

0.36 0.44

0.39 0.20 0.32

0.46 0.47 0.46 0.40 0.40 0.33

0.49 0.21 0.40

ADL

0.36 0.37

0.34 0.41

0.43 0.33 0.21

0.46 0.50 0.55 0.47 0.50 0.42

0.55 0.39 0.23

I-ADL

0.49 0.63

0.57 0.54

0.69 0.49 0.43

0.53 0.57 0.48 0.59 0.54 0.65

0.67 0.50 0.40

S-ADL

ADL = Activities of Daily Living; CDT = Clock Drawing Test; DRS = Dementia Rating Scale; GAF = Global Assessment of Functioning Scale; HSCT = Hayling Sentence Completion Test; IADL = Instrumental Activities of Daily Living; MMSE = Mini Mental State Examination; RCFT = Rey Complex Figure Test; S-ADL = Social Activities of Daily Living; TMT–A = Trail Making Test –part A; TMT–B = Trail Making Test–part B. a Spearman correlation analysis, adjusted on Fisher’s exact Test with p < 0.05.

BACS Global score List Learning Digit Sequencing Task Token Motor Task Verbal fluency Semantic Alphabetical Symbol Coding Tower of London Test BACS, Z-scores Global score List Learning Digit Sequencing Task Token Motor Task Verbal fluency (semantic and alphabetical) Symbol Coding Tower of London Test

Correlations

HSCT first part

Table 5. Correlations between the results of the Brief Assessment of Cognition in Schizophrenia (BACS) and the standard cognitive test battery and the functional scores for patients with bipolar disordera

Using the BACS in older patients with BD

333

Cholet et al. able to withstand four hours of testing were recruited. Some authors have suggested that the number of suicide attempts may influence the cognitive profile of patients with BD (32). In our study, only a few patients with BD had made suicide attempts, thereby precluding us from analyzing the possible confounding effects of being a ‘survivor’. Moreover, our patients were recruited from a specific geographical region, possibly introducing a geographical bias. Therefore, we remain cautious about generalizing our results to broader populations of elderly patients with BD. Third, our study design may have had limitations. The long duration of the interviews may have altered the patients’ test performance and introduced errors, although the patients were given the option to take breaks as needed. Moreover, they were asked to attend for two separate interviews. Although an assessment of thymic state occurred at each visit, we cannot rule out the possibility that we failed to consider the wide individual variability in cognitive impairment, described by Depp and colleagues (71), in the short term. In addition, the same examiner administered all of the tests, and the GAF was performed at the end of the second interview; this approach may have introduced an examiner bias, leading us to underestimate the GAF score in light of the results obtained on the cognitive functioning tests. The recommendations by the ISBD Cognition Committee highlight the importance of developing a specific cognitive scale both for patients with BD and with SCZ. According to this committee, this scale should assess psychomotor speed (e.g., Symbol Coding Test), executive functions (e.g., Verbal Fluency and Tower of London Test), attention (e.g., Token Motor Task), verbal memory (e.g., List Learning), working memory (e.g., Digit Sequencing Task), and visual memory (45). The BACS assesses all of the above-mentioned cognitive domains, except for visual memory. However, the results of our study showed that the BACS scores are correlated with visual memory, as assessed by recall on the RCFT. This finding raises important questions concerning the role and importance of visual memory in executive functions. Thus, the relevance of adding a test of visual memory for elderly patients with BD may be questionable. The ISBD Cognition Committee also call into question the value of assessing cognitive inhibition, particularly using the HSCT. Considering that the results of the HSCT appear to be correlated with several sub-scores of the BACS, the HSCT likely tests a combination of several major cognitive functions that are evaluated separately in

334

the BACS. In addition, the Tower of London Test does not appear to be correlated with the subjects’ educational level, and the latter can be measured more reliably. Thus, we posit that the HSCT could be administered as a second-line test in elderly patients with BD, particularly if the result obtained using the Tower of London Test is correct. Conclusions

The BACS may be a valuable neuropsychological instrument for assessing global cognition in elderly patients with BD, with a high sensitivity for detecting cognitive manifestations of the BD process. Moreover, the global score may serve as a powerful indicator of functional outcome. Due to its brevity (under 35 min) and its higher sensitivity compared to the MMSE, the BACS could effectively be integrated into a psychiatric follow-up consultation. These results are promising and merit replication in a larger sample to better explore the impact of potential confounding factors such as BD type, the age at onset, the number of hospitalizations, the treatments (especially lithium), and aging. Finally, the results of our study incorporate the most recent data from the literature (72), and emphasize the importance of developing specialized care tailored to patients with BD, with the aim of preventing the emergence of cognitive disorders and downstream effects on psychosocial functioning. Our study also raises the possibility that prevention strategies against cognitive impairment used in SCZ, such as cognitive rehabilitation and functional remediation (73), could be adapted to help patients with BD. Disclosures The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.

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