Bobes García, J1, García-Portilla, Paz¹, Fillat, O²

1 Medicine Department, Psychiatry Area, University of Oviedo, Oviedo, Spain. 2 Sanofi-Aventis, Medical Department, Spain.

On behalf of the EPICOG Study Group Contact: bobes-bascaran@telefonica.net

BACKGROUND

Data concerning prevalence rates of cognitive impairment in

outpatients with schizophrenia is scarce. As cognitive status has

been found to be a good predictor of the functional status in

schizophrenia (occupational activity, independent living status, etc.)

the availability of such data will provide useful information for use in

patients’ functional counseling.

OBJECTIVE

To establish the relation between cognitive performance and

functional status in outpatients with schizophrenia under

maintenance treatment with atypical antipsychotics.

METHODS

Cross-sectional, naturalistic, follow-up study conducted in 234

clinical settings in Spain (Community Mental Health Centres).

Patients: Outpatients with a diagnosis of schizophrenic disorder

(DSM-IV-TR criteria) under maintenance treatment with at least one

atypical antipsychotic at stable dosage for at least six months.

Assesment: Information regarding sociodemographic (including work

status, legal disability statement and financial resources) and clinical

profile was recorded. Clinical severity was assessed by CGI-SCH

and disability by WHO-DAS-II. Cognitive evaluation was made using

the Experimental Cognitive Battery: EPICOG-Beta. Epicog-Beta

included cognitive domains documented to be correlated to

functional outcomes according to MATRICS revision: Working

Memory (WAIS-III letter-number sequencing), Executive function

(semantic fluency –animals, fruits, cities-), Processing speed (WAIS-

III digit symbol coding and semantic fluency), and Verbal memory

(logic memory WMS-III-Text A).

Statistical analysis: Results for cognitive testing are reported as

mean and SD for raw scores; for prevalence data as result of 1 SD,

1.5 SD and 2 SD below the mean (scoring < 7, < 5.5 and < 4

respectively). Prevalence rates were determined following the

standardization of patient’s scores according to country’s normative

information (when available).

RESULTS

672 outpatients were recruited by 257 investigators.

Sociodemographic characteristics are displayed in tables 1 and 2.

18.2% were working while el 50.3% had a governmental statement

of permanent working disability. The most frequent schizophrenia

subtype was paranoid (75.3%), 8.9% had residual subtype.

Comorbidity with substance abuse was reported for 24.6% of the

patients. CGI-SCH subscale scores are shown in figure 1.

Cognitive and functional results: 62% of the patients had some level

of cognitive impairment according to the CGI-SCH cognitive

subscale score (> 3) (figure 2). EPICOG-Beta results [raw scores,

mean (SD)]: Letter-number sequencing 8.5 (3.9); Semantic fluency –

animals 14 (5.6), fruits 10 (3.6), and cities 15.5 (8.1)-; Immediate

verbal memory –units 10.4 (4.6) and issues 4.6 (1.7)-; Digit-symbol

coding 43.6 (21.5).

Following standardization to scalar scores for WAIS-III and WMS-III

subtests (figure 3), prevalence rates were obtained (table 3). The

majority of patients with schizophrenia showed impaired executive

function tasks (semantic fluency) according to normative data. They

also showed impairment in processing speed, and verbal and

working memories although at lower rates (table 3). The level of

disability in the 4 domains assessed is shown in figure 4.

Performance in cognitive tests and level of disability were

significantly and inversely correlated (table 5). Those patients who

were working scored significantly higher in the EPICOG battery

(table 6).

CONCLUSION

• There is a high prevalence of cognitive impairment in outpatients

with schizophrenia under atypical antipsychotic maintenance

treatment.

• Cognitive performance is significantly correlated with level

disability (inverse correlation) and working status.

• Future research should address the predictive value of the

EPICOG battery in relation to functional outcomes.

ACKNOWLEDGMENTS

The EPICOG study was founded by sanofi-aventis. The authors

thank Dolors Badenes (Mutua de Terrasa Hospital), Manuel de

Gracia (University of Girona), Silvia Zaragoza, Mireia Puig and

Beatriz Gancedo (PSYNCRO, Neuropsychological Research

Organization, S.L. ) for their contribution to the EPICOG project.

REFERENCES

(1) Green MF, Kern RS, Heaton RK. Longitudinal studies of cognition and functional

outcome in schizophrenia: implications for MATRICS. Schizophr Res 2004 December

15;72(1):41-51.

(2) Hofer A, Baumgartner S, Bodner T et al. Patient outcomes in schizophrenia II: the

impact of cognition. Eur Psychiatry 2005 August;20(5-6):395-402.

(3) Green MF, Kern RS, Braff DL, Mintz J. Neurocognitive deficits and functional

outcome in schizophrenia: are we measuring the "right stuff"? Schizophr Bull

2000;26(1):119-36.

(4) Wechsler D. Escala de Memoria de Wechsler para Adultos: Manual de

Aplicación y Corrección. Madrid: TEA Ediciones; 2001.

(5) Escala de Interligencia de Wechsler para Adultos - III: Manual Técnico. Madrid:

TEA Ediciones; 2001.

20th ECNP Congress

Vienna, Austria, October 13-17, 2007

Poster number: P.3.c.037

SAMPLE DESCRIPTION

Universidad de Oviedo

Table 1. Descriptives

Evaluable patients 672

Sex

Male 67.2%

Female 32.8%

Age

Mean 39.0 SD 10.5

Marital Status

Single 76.1%

Partner 13.2%

Other 7.9 %

Table 2. Descriptives

Education level %

No Studies 9.8

Primary study 46.4

Secondary studies 33.6

University studies 8.9

Patients with cognitive impairment according CGI-SCH- (Cognitive Subscale CGI-SCH scoring 2)*

ICG-SCH

5%

25%

32%

24%

13%

2%

0%

25%

34%

19%

15%

6%

2%

0%

9%

21%

26%

24%

16%

4%

0%

36%

40%

15%

6%

2%

0%

0%

9%

29%

30%

19%

11%

2%

0%

0% 5% 10% 15% 20% 25% 30% 35% 40% 45%

1. Normal, not ill

2. Minimally ill

3. Mildly ill

4. Moderately ill

5. Markedly ill

6. Severely ill

7. Among the most

severely ill

Patients

Cognitive Symptoms

Depressive Symptoms

Negative Symptoms

Positive Symptoms

Overal Severity

Disfunction of patients according to World Health

Organization Disability Assessment Schedule (WHO-DAS-S)

0

5

10

15

20

25

30

35

40

No disability 1 2 3 4 Gross disability

Disability degree

Perc

enta

ge

Personal Care

Occupation

Family and Housholding

Broader Social context

ICG-SCH

9%

29%

30%

19%

11%

2%

0%

0% 5% 10% 15% 20% 25% 30% 35% 40% 45%

1. Normal, not ill

2. Minimally ill

3. Mildly ill

4. Moderately ill

5. Markedly ill

6. Severily ill

7. Among the most

severily ill

Seriousness

Patients

Cognitive Symptoms

n= 599 91.2%

Patients with self reported cognitive dificulties

n= 524 78%

5 10 25

15.7%

Expected performance according

to Normal Distribution

Obteined performance

COGNITIVE PERFORMANCE AND FUNCTIONAL STATUS

CUIDADO

PERSONAL

FUNCIONAMIENTO

FAMILIAR

Patients with previous cognitive assesment

n= 83 12.5%

WORK CAPACITY

BROADER SOCIAL

CONTEXT

OCCUPATION

FAMILY AND

HOUSEHOLD

PERSONAL

CARE

Gross disability No disability

Neuropsychological performance and cognitive

dysfunction in outpatients with schizophrenia :

Relationship with functional outcomes

CLINICAL PROFILE

COGNITIVE PROFILE

EXPERIMENTAL COGNITIVE BATTERY:

EPICOG-Beta

COGNITIVE PERFORMANCE

Severi

ty

Table 9. Results in Cognitive Tests (Direct Score)

Active Working Status

n=204

Non Active Woring Status n=417

Sign.

Cognitive Test Mean SD Mean SD

Letter-number sequencing 9.3 4.0 8.3 3.9 P=0.0023 Sign.

Digit-symbol coding 49.5 20.1 40.7 20.5 P<0.0001 Sign.

Semantic Fluency 43.1 16.6 38.3 15.0 P=0.0014 Sign.

Animals 15.2 6.0 13.5 5.6 P=0.022 Sign.

Fruits 10.7 3.6 9.8 3.5 P=0.0091 Sign.

Cities/Villages 17.19 8.8 15.01 7.83 P=0.0026 Sign.

Memory*:Units 11.8 4.6 9.9 4.6 P<0.0001 Sign.

Memory*: Issues 5.1 1.5 4.4 1.7 P<0.0001 Sign.

* Refered only to one text in a test of inmediate recall (Text A)

Table 8. Correlations between Results in Cognitive Tests and Funcional State (Direct Raws)

WHO-DAS

Personal Care

WHO-DAS

Family and household

WHO-DAS

Occupation

WHO-DAS

Broader Social Context

WHO-DAS

Total

Cognitive test r p r p r p r p r p

Letter-number sequencing -0.37 <0.0001 -0.30 <0.0001 -0.30 <0.0001 -0.31 <0.0001 -0.39 <0.0001

Digit-symbol coding -0.31 <0.0001 -0.25 <0.0001 -0.27 <0.0001 -0.27 <0.0001 0.33 <0.0001

Semantic Fluency -0.30 <0.0001 -0.25 <0.0001 -0.27 <0.0001 -0.28 <0.0001 -0.33 <0.0001

Animals -0.27 <0.0005 -0.23 <0.0001 -0.27 <0.0001 -0.24 <0.0001 -0.31 <0.0001

Fruits -0.30 <0.0001 -0.22 <0.0003 -0.24 <0.0001 -0.24 <0.0001 -0.29 <0.0001

Cities/Villages -0.27 <0.0001 -0.23 <0.0001 -0.23 <0.0001 -0.27 <0.0001 -0.30 <0.0001

Memory* : Units -0.24 <0.0001 -0.23 <0.0001 -0.21 <0.0001 -0.25 <0.0001 -0.28 <0.0001

Memory* : Issues -0.15 <0.0001 -0.19 <0.0007 -0.14 <0.0001 -0.19 <0.0001 -0.21 <0.0001

WHO-DAS: World Health Organization Disability assessment Scale Short Version

Table 7. Results of World Health Organization Disability Assessment

Schedule (WHO-DAS-S)

Functioning with

assistance SubScales Mean SD Median

Min Max

n %

Personal Care 1.1 1.1 1 0 5 46 6.9

Occupation 2.5 1.4 2 0 5 56 8.4

Family and household 1.9 1.2 2 0 5 47 7.0

Broader Social Context 2.6 1.3 3 0 5 53 7.9

Total 7.9 4.1 8 0 19 - -

Table 3.

Area Subtest

Working Memory Letter-number sequencing

Executive Function Semantic fluency*

Processing speed Digit-symbol coding

Verbal Memory Logic memory

Table 4.

Subtest Time

(according patient’s performance)

1. Letter-Number sequencing (WAIS-III) 5’-15’

2. Categorial Fluency (4 categories)

5’

3. Digit-Symbol Coding (WAIS-III) 5’

4. Logic Memory (recuerdo de un texto-WMS)

6’ – 10’

Total expected Time 21’ – 30’

13,6% 2,1%

Table 5.

Percentage of Patients at Defined Cut-Off Limits Cognitive Subtest

1SD 1.5SD 2SD

Letter Number Sequence* 38.2 21.1 12.8

Digit-Symbol Coding* 63.4 38.5 28.5

Verbal Memory**

Units 34.4 25.2 12.4

Issues 25.7 12.0 6.0

Centil_25 Centil_10 Centil_5

Semantic Fluency***

Animals 86.3 68.3 60.3

Fruits 97.5 86.9 77.3

* WAIS-III Subtests, **WMS-III Subtests, *** For category “cities” no normative data was available.

For scalar standardized measures, cut-off values of 1 SD, 1.5 SD and 2 SD corresponds to scoring 7, 5.5 and 4 respectively.

Area Subtest Age Gender Education

Working Memory Letter-number sequencing p = 0.000014

Elder normative sample, wider dispersion.

p < 0.0001

EPICOG study more men than women.

p < 0.0001

Normative sample, more cases without primary

education.

Executive Function Semantic fluency* Ns p < 0.0001

EPICOG study more men than women.

p < 0.0001

Normative sample, more cases with university

degree.

Processing speed Digit-symbol coding p = 0.0001

Elder normative sample, wider dispersion.

p < 0.0001

EPICOG study more men than women.

p < 0.0001

Normative sample, more cases without primary

education.

Verbal Memory Logic memory p = 0.0001

Elder normative sample, wider dispersion. p = 0.0001 Unknowed*

The normative sample used to standardized semantic fluency test, was evaluated during a pilot study with adults between 20 and 49 years old ( Buriel Y, Gramunt N, Bohm P, Rodes E, Peña-Casanova J. Verbal fluency: preliminary normative data in a Spanish sample of young adults (20-49 years

of age) Neurologia. 2004 May;19(4):153-9. Spanish]

* Spanish normative data do not provide information about education

Figure 1.

Figure 2.

Figure 4.

Figure 5.

Figure 6.

Table 6.

SELFREPORTED COGNITIVE DIFICULTIES

Yes

78%

No

20%

Uncertain

problems

2%

Figure 3.

• Functioning with assistance