The MATRICS Consensus Cognitive Battery (MCCB): Co-norming and standardization in Spain

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Abstract

The MATRICS Consensus Cognitive Battery (MCCB), developed by the National Institute of Mental Health (NIMH) Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative, has been recommended as the standard battery for clinical trials of cognition-enhancing interventions for schizophrenia. Normative data for the MCCB has been previously obtained in the U.S. Extrapolation of these normative data to different countries may be problematic due to the translation of the different tests, as well as potential cultural influences. We present the process of obtaining normative data for the MCCB in Spain with administration of the battery to a general community standardization sample. In addition, we examine the influence of age, gender, and educational level on test performance. The MCCB was administered to a total sample of 210 healthy volunteers, at three Spanish sites. For each site, recruitment of the sample was stratified according to age, gender, and educational level. Our findings indicate significant age, gender, and education effects on the normative data for the MCCB in Spain, which are comparable to those effects described for the original standardized English version in the U.S. The fact that the normative data are comparable, and that the variables age, gender, and education have a similar influence on performance, supports the robustness of the MCCB for use in different countries.

Introduction

The existence of cognitive impairment in schizophrenia, already a central feature in Kraepelin's original concept of dementia praecox (Kraepelin, 1919), is nowadays well accepted and documented (Heinrichs and Zakzanis, 1998, Bowie and Harvey, 2005). Cognitive dysfunction is considered to be a core component of schizophrenia (Elvevåg and Goldberg, 2000) that is already present at the time of the first psychotic episode (Galderisi et al., 2009, Mesholam-Gately et al., 2009). Despite the fact that cognitive impairment is considered to be one of the main factors influencing community functioning and prognosis in schizophrenia (Green et al., 2000, Green et al., 2004, Bowie et al., 2008, Jabben et al., 2010, Fett et al., 2011), the existing therapeutic options have not shown the desired impact on cognition. Thus, there is a growing interest in the field in developing medications with potential efficacy for improving cognitive deficits in schizophrenia. Only limited existing evidence supports cognition-enhancing agents for schizophrenia (Galletly, 2009, Barch, 2010), and the studies that do exist are difficult to compare because they investigated different cognitive domains and used different measurement approaches to evaluate cognitive function. This lack of standardization has been a serious limitation for drawing conclusions across studies for novel therapeutic options for cognitive dysfunction in schizophrenia (Nuechterlein et al., 2008).

One of the primary goals of the NIMH contract, Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS), was to develop a consensus cognitive battery for use in clinical trials to address the measurement obstacle in this area of drug discovery. After a first phase of the MATRICS initiative in which seven cognitive domains were selected (Nuechterlein et al., 2004), the MATRICS Consensus Cognitive Battery (MCCB) was developed. This battery includes ten neuropsychological tests selected to be optimal for measuring change in clinical trials and assessing the cognitive domains commonly examined in studies of schizophrenia (Nuechterlein et al., 2008). The MCCB tests, grouped by cognitive domain, are as follows: Trail Making Test, Part A; Brief Assessment of Cognition in Schizophrenia, symbol coding subtest; Category fluency test, animal naming (Speed of Processing); Continuous Performance Test, Identical Pairs version (Attention/Vigilance); Wechsler Memory Scale, 3rd ed., spatial span subtest; Letter–Number Span test (Working Memory); Hopkins Verbal Learning Test—Revised (Verbal Learning); Brief Visuospatial Memory Test—Revised (Visual Learning); Neuropsychological Assessment Battery, mazes subtest (Reasoning and Problem Solving); and Mayer–Salovey–Caruso Emotional Intelligence Test, managing emotions branch (Social Cognition) (Nuechterlein et al., 2008).

The MCCB is composed of tests for which there are existing normative data. However, the fact that different tests have been selected, grouped together, and presented in a certain order, means that co-norms (i.e. normative data for the battery administered as a unit) are important for test score interpretation (Kern et al., 2004, Russell et al., 2005). Thus, the MATRICS Neurocognition Committee decided that a standardization and co-norming process would be required to allow MCCB results to be adequately interpreted. In the study by Kern et al. (2008), normative data for the US were obtained, and the influence of age, gender and educational level on the performance of the different tests was evaluated. Age effects were found across tests, with younger subjects performing better on most tests. Likewise, educational level was significantly associated with all cognitive domains; those with higher education showed better performance. Finally, gender was associated with differences in working memory, reasoning and problem solving, and verbal learning performance, whereas no gender differences were found in the other cognitive domains, or in the overall composite score.

Extrapolation of these normative data to different countries is problematic due to the translation of the different tests, as well as potential cultural influences. Translation and cultural issues can inadvertently change the difficulty level of test items even when professional translators are used (Hambleton et al., 2005). It is highly recommended that normative data be obtained for the country and language in which the MCCB is to be used. In this article, we present the process of obtaining normative data for the MCCB in Spain with administration to a community standardization sample. The intention was to collect norms that would be used to score the version of the MCCB that is administered in Spain. In addition, we examine the influence of age, gender, and educational level on test performance.

Section snippets

Participants

The study sample was recruited in three different sites in Spain: Madrid, Zaragoza and Cuenca. The sites were chosen to be representative of a large city with an urban population (Madrid, over 3 million inhabitants), an intermediate sized city (Zaragoza, over 600,000 inhabitants) with a partially rural component, and a small city (Cuenca, over 50,000 inhabitants) with a significant rural component. As in the Kern et al. (2008) study, the sample was stratified according to age, gender, and

Results

Distribution of scores for three of the ten tests were found to have a marked skew: TMT, Fluency (negative skew), and BVMT-R (positive skew). The TMT and Fluency scores were transformed using a logarithmic transformation, and a y = x2 transformation was used for BVMT-R scores. T scores were then obtained for each of the seven cognitive domains, as well as for the overall composite score, as explained previously.

Discussion

Our findings indicate a significant influence of age, gender, and education within the normative data for the MCCB in Spain, comparable to the effects described for the original standardized English version in the US.

Regarding age effects, poorer performance is generally found as age progresses, with significant differences for all cognitive domains except for social cognition. Although many studies in healthy subjects have shown age-related decreases in cognitive performance including several

Role of funding source

This research was supported in part by grant PI080514 (Fondo de Investigaciones Sanitarias, FIS) and by the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) of the Instituto de Salud Carlos III.

Contributors

RRJ, KHN, MFG, RSK and TP designed the study and wrote the protocol. AB, JLS, AL and MAJA managed the literature searches and analyses. MMO, RLA, AIA, CGN, AB, MAJA, AL and JLS selected the sample, evaluated patients and contributed in some aspects of the study design and in the interpretation of results. RRJ, AB and TP undertook the statistical analysis. RRJ, AB, and TP wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.

Conflict of interest

Although not related to this work, Dr. Nuechterlein has consulted for Endo Pharmaceuticals, Johnson and Johnson, Merck, and Wyeth and has an investigator-initiated research grant from Ortho-McNeil Janssen Scientific Affairs.

Although not related to this work, Dr. Green has been a consultant to Amgen, Abbott Laboratories, Cypress, Dainippon Sumitomo Pharma, Lundbeck, Otsuka, Sanofi-Aventis Pharmaceuticals, Takeda and Teva. He has been a speaker for Janssen Cilag, Otsuka, and Sunovion.

Dr. Kern

Acknowledgment

We thank the Instituto de Investigación Hospital 12 de Octubre and the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) of the Instituto de Salud Carlos III.

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