Lyle E. Baade

The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity.

OBJECTIVE The lack of an accepted standard for measuring cognitive change in schizophrenia has been a major obstacle to regulatory approval of cognition-enhancing treatments. A primary mandate of the National Institute of Mental Healths Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was to develop a consensus cognitive battery for clinical trials of cognition-enhancing treatments for schizophrenia through a broadly based scientific evaluation of measures. METHOD The MATRICS Neurocognition Committee evaluated more than 90 tests in seven cognitive domains to identify the 36 most promising measures. A separate expert panel evaluated the degree to which each test met specific selection criteria. Twenty tests were selected as a beta battery. The beta battery was administered to 176 individuals with schizophrenia and readministered to 167 of them 4 weeks later so that the 20 tests could be compared directly. RESULTS The expert panel ratings are presented for the initially selected 36 tests. For the beta battery tests, data on test-retest reliability, practice effects, relationships to functional status, practicality, and tolerability are presented. Based on these data, 10 tests were selected to represent seven cognitive domains in the MATRICS Consensus Cognitive Battery. CONCLUSIONS The structured consensus method was a feasible and fair mechanism for choosing candidate tests, and direct comparison of beta battery tests in a common sample allowed selection of a final consensus battery. The MATRICS Consensus Cognitive Battery is expected to be the standard tool for assessing cognitive change in clinical trials of cognition-enhancing drugs for schizophrenia. It may also aid evaluation of cognitive remediation strategies.

The MATRICS Consensus Cognitive Battery, Part 2: Co-Norming and Standardization

OBJECTIVE The consensus cognitive battery developed by the National Institute of Mental Healths (NIMHs) Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative includes 10 independently developed tests that are recommended as the standard battery for clinical trials of cognition-enhancing interventions for schizophrenia. To facilitate interpretation of results from the MATRICS Consensus Cognitive Battery using a common scaling across tests, normative data were obtained from a single representative U.S. community sample with the battery administered as a unit. METHOD The MATRICS Consensus Cognitive Battery was administered to 300 individuals from the general community at five sites in differing geographic regions. For each site, recruitment was stratified by age, gender, and education. A scientific survey sampling method was used to help avoid sampling bias. The battery was administered in a standard order to each participant in a single session lasting approximately 60 minutes. Descriptive data were generated, and age, gender, and education effects on performance were examined. RESULTS Prominent age and education effects were observed across tests. The results for gender differed by measure, suggesting the need for age and gender corrections in clinical trials. The MATRICS Consensus Cognitive Battery components were co-normed, with allowance for demographic corrections. CONCLUSIONS Co-norming a battery such as the MATRICS Consensus Cognitive Battery, comprising tests from independent test developers each with their own set of norms, facilitates valid interpretation of test scores and communication of findings across studies. These normative data will aid in estimating the magnitude of change during clinical trials of cognition-enhancing agents and make it possible to derive more directly interpretable composite scores.

Neuropsychological test results associated with psychiatric disorders in adults.

This review addresses the question of whether neuropsychological tests can be used to discriminate between cerebral dysfunction and nonorganic psychiatric disorders. Considered are 94 studies that compared test scores of psychiatric patients with scores of brain-damaged patients or with established norms for organicity. Despite methodological inconsistencies and deficiencies across studies, most studies found that psychiatric diagnostic groups other than chronic or process schizophrenics performed better than organics on testing. Organic versus functional discrimination rates reported in these studies are similar to discrimination rates obtained by the tests when organics are compared with normal or general medical controls. Considered together with organicity base rate and error cost estimates, these discrimination rates are high enough to justify the use of most popular neuropsychological tests in psychiatric settings that do not have high proportions of chronic or process schizophrenics. The possibility is discussed that groups of chronic or process schizophrenics may look organic on neuropsychological tests because a significant proportion of such patients are organic.

Functional Co-Primary Measures for Clinical Trials in Schizophrenia: Results From the MATRICS Psychometric and Standardization Study

OBJECTIVE During the consensus meetings of the National Institute of Mental Health Measurement and Treatment Research to Improve Cognition in Schizophrenia (NIMH-MATRICS) Initiative, the U.S. Food and Drug Administration took the position that a drug for this purpose should show changes on 1) an accepted consensus cognitive performance measure and 2) an additional measure (i.e., a co-primary) that is considered functionally meaningful. The goal of the current study was to describe steps to evaluate four potential co-primary measures for psychometric properties and validity. METHOD As part of the five-site MATRICS Psychometric and Standardization Study (PASS), two measures of functional capacity and two interview-based measures of cognition were evaluated in 176 patients with schizophrenia (167 of these patients were retested 4 weeks later). RESULTS Data are presented for each co-primary measure for test-retest reliability, utility as a repeated measure, relationship to cognitive performance, relationship to functioning, tolerability/practicality, and number of missing data. CONCLUSIONS Psychometric properties of all of the measures were considered acceptable, and the measures were generally comparable across the various criteria, except that the functional capacity measures had stronger relationships to cognitive performance and fewer missing data. The development and evaluation of potential co-primary measures is still at an early stage, and it was decided not to endorse a single measure for clinical trials at this point. The current findings offer the initial steps to identify functionally meaningful co-primary measures in this area and will help to guide further evaluation of such measures.

The MCCB impairment profile for schizophrenia outpatients: Results from the MATRICS psychometric and standardization study

The MATRICS Psychometric and Standardization Study was conducted as a final stage in the development of the MATRICS Consensus Cognitive Battery (MCCB). The study included 176 persons with schizophrenia or schizoaffective disorder and 300 community residents. Data were analyzed to examine the cognitive profile of clinically stable schizophrenia patients on the MCCB. Secondarily, the data were analyzed to identify which combination of cognitive domains and corresponding cut-off scores best discriminated patients from community residents, and patients competitively employed vs. those not. Raw scores on the ten MCCB tests were entered into the MCCB scoring program which provided age- and gender-corrected T-scores on seven cognitive domains. To test for between-group differences, we conducted a 2 (group)×7 (cognitive domain) MANOVA with follow-up independent t-tests on the individual domains. Classification and regression trees (CART) were used for the discrimination analyses. Examination of patient T-scores across the seven cognitive domains revealed a relatively compact profile with T-scores ranging from 33.4 for speed of processing to 39.3 for reasoning and problem-solving. Speed of processing and social cognition best distinguished individuals with schizophrenia from community residents; speed of processing along with visual learning and attention/vigilance optimally distinguished patients competitively employed from those who were not. The cognitive profile findings provide a standard to which future studies can compare results from other schizophrenia samples and related disorders; the classification results point to specific areas and levels of cognitive impairment that may advance work rehabilitation efforts.

Reliable Digit Span: a systematic review and cross-validation study.

Reliable Digit Span (RDS) is a heavily researched symptom validity test with a recent literature review yielding more than 20 studies ranging in dates from 1994 to 2011. Unfortunately, limitations within some of the research minimize clinical generalizability. This systematic review and cross-validation study was conducted to address these limitations, thus increasing the measure’s clinical utility. Sensitivity and specificity rates were calculated for the ≤6 and ≤7 cutoffs when data were globally combined and divided by clinical groups. The cross-validation of specific diagnostic groups was consistent with the data reported in the literature. Overall, caution should be used when utilizing the ≤7 cutoff in all clinical groups and when utilizing the ≤6 cutoff in the following groups: cerebrovascular accident, severe memory disorders, mental retardation, borderline intellectual functioning, and English as a second language. Additional limitations and cautions are provided.

Validation of MMPI-2-RF validity scales in criterion group neuropsychological samples.

This study utilized multiple criterion group neuropsychological samples to evaluate the “over-reporting” and “under-reporting” MMPI-2-RF validity scales. The five criterion groups included in this study were (1) litigating traumatic brain injury patients who failed Slick et al. criteria for probable malingering, (2) litigating traumatic brain injury patients who passed Slick et al. criteria, (3) mixed neuropsychological outpatients who passed SVTs and were diagnosed with primary neurological conditions, (4) mixed neuropsychological outpatients who passed SVTs and were diagnosed with primary psychiatric conditions, and (5) epileptic seizure disorder inpatients who were diagnosed via video-EEG. Using the data from these groups, cumulative percentages for all possible T-scores and sensitivity and specificity rates for optimal cutoff scores were determined. When specificity rates were set at 90% across all non-malingering neurological condition groups, sensitivity rates ranged from 48% (FBS-r) to 10% (K-r).

Assessment of quality of life among the elderly with epilepsy.

As the elderly represent the most rapidly growing population in the United States, it is critical that physicians are capable of managing their chronic illnesses, including epilepsy. Optimal treatment of epilepsy integrates an understanding of health-related quality of life (HRQOL), yet limited information is available to guide HRQOL issues among the elderly. This study found that seniors with epilepsy do not have poorer HRQOL compared with general epilepsy populations. However, when compared with general populations without epilepsy, seniors with epilepsy report a significantly lower HRQOL across all domains. Multiple factors may uniquely affect HRQOL among elderly populations with epilepsy: aging, comorbid conditions, and epilepsy variables. However, to our knowledge, no one instrument addresses all of these aspects. The development of HRQOL instruments specifically for an elderly population with epilepsy may be useful and needed.

Bifactor and Item Response Theory Analyses of Interviewer Report Scales of Cognitive Impairment in Schizophrenia

A psychometric analysis of 2 interview-based measures of cognitive deficits was conducted: the 21-item Clinical Global Impression of Cognition in Schizophrenia (CGI-CogS; Ventura et al., 2008), and the 20-item Schizophrenia Cognition Rating Scale (SCoRS; Keefe et al., 2006), which were administered on 2 occasions to a sample of people with schizophrenia. Traditional psychometrics, bifactor analysis, and item response theory methods were used to explore item functioning and dimensionality and to compare instruments. Despite containing similar item content, responses to the CGI-CogS demonstrated superior psychometric properties (e.g., higher item intercorrelations, better spread of ratings across response categories) relative to the SCoRS. The authors argue that these differences arise mainly from the differential use of prompts and how the items are phrased and scored. Bifactor analysis demonstrated that although both measures capture a broad range of cognitive functioning (e.g., working memory, social cognition), the common variance on each is overwhelmingly explained by a single general factor. Item response theory analyses of the combined pool of 41 items showed that measurement precision is peaked in the mild to moderate range of cognitive impairment. Finally, simulated adaptive testing revealed that only about 10 to 12 items are necessary to achieve latent trait level estimates with reasonably small standard errors for most individuals. This suggests that these interview-based measures of cognitive deficits could be shortened without loss of measurement precision.

NEUROPSYCHOLOGICAL TESTING AND ASSESSMENT SCALES FOR DEMENTIA OF THE ALZHEIMER'S TYPE

Neuropsychological assessment plays an important role in the process of diagnosing DAT. Whereas the brief screens are sensitive to the cognitive deficits associated with DAT, full battery measures should be used to rule out early dementia or to differentiate among the various dementing illnesses. Following diagnosis, there are numerous assessment measures that facilitate management and placement decisions. These measures include instruments that help stage the illness to determine severity, instruments that evaluate the patients capacity to perform activities of daily living, and measures that evaluate for the behavior symptoms common in later-stage dementia.