MATRICS Consensus Cognitive Battery Domain Scores Research Articles

A Randomized Trial to Assess the Efficacy and Safety of ABT-126, a Selective α7 Nicotinic Acetylcholine Receptor Agonist, in the Treatment of Cognitive Impairment in Schizophrenia

The authors sought to evaluate the efficacy and safety of ABT-126, a selective α7 nicotinic receptor partial agonist, in stable patients with schizophrenia. A 12-week, double-blind, placebo-controlled, parallel-group phase 2 study was conducted in 22 centers in the United States. Clinically stable patients with schizophrenia were randomly assigned to receive once-daily dosing with 10 mg of ABT-126, 25 mg of ABT-126, or placebo. The primary efficacy measure was change from baseline to week 12 on the MATRICS Consensus Cognitive Battery (MCCB) composite score compared with placebo, tested by a one-sided t test. Secondary measures included MCCB domain scores and UCSD Performance-Based Skills Assessment total score, each tested by two-sided t tests. A total of 207 subjects were randomized, of whom 165 (81%) completed the study. ABT-126 showed an improvement that fell short of significance on the MCCB composite score at week 12 (least squares mean difference from placebo, 1.3 and 1.5 for the 10 mg and 25 mg groups, respectively). A significant treatment-by-smoking status interaction was observed on the mean change from baseline to final MCCB composite score: nonsmokers (N=69) demonstrated a difference from placebo of 2.9 (SE=1.4) in the 10 mg group and 5.2 (SE=1.6) in the 25 mg group, whereas no differences were observed in smokers (N=113). Among the nonsmokers in the ABT-126 25 mg group (N=19), significant improvements compared with placebo occurred at final assessment for verbal learning (least squares mean difference=5.5, SE=1.9), working memory (least squares mean difference=5.4, SE=2.0), and attention/vigilance (least squares mean difference=8.7, SE=2.5). The most frequently reported adverse events for ABT-126 were dizziness, diarrhea, and fatigue (all <8% incidence). ABT-126 demonstrated a procognitive effect in nonsmoking subjects, particularly in verbal learning, working memory, and attention.

Neurocognitive normality in schizophrenia revisited

The validity and significance of normal range neurocognition in schizophrenia remain unclear and controversial. We assessed whether normal range patients and controls demonstrate evidence of decline relative to premorbid ability and differ in performance profiles across measures, including those external to the normality criterion. In addition, we compared below normal range healthy control participants with patients at the same ability level. Performance normality was defined as a MATRICS Consensus Cognitive Battery (MCCB) composite T score between 40 and 60. Patients (n=17) and controls (n=24) meeting the criterion were compared on MCCB domain scores and on independent measures of reading ability, probabilistic and social reasoning. Patients (n=19) and controls (n=20) scoring below 40 on the MCCB composite were compared on the same set of measures. Cognitively normal range patients and controls did not differ on estimated premorbid ability or decline and differed only on the Processing Speed domain of the MCCB. Performance did not differ across other domains or on social and probabilistic reasoning tasks. Cognitively below normal range patients and controls showed marked discrepancies between premorbid and current ability, but there were no group differences. In addition, below normal range groups did not differ on any MCCB domain score or in terms of external cognitive measures. Cognitively normal range schizophrenia patients may be largely indistinguishable from normal range controls, with the exception of processing speed performance. More typical schizophrenia patients below the normal range may be indistinguishable from low-performing controls even in terms of processing speed.

The effect of electroconvulsive therapy on neurocognitive function in treatment-resistant bipolar disorder depression.

To compare the effects of right unilateral (RUL) electroconvulsive therapy (ECT) and algorithm-based pharmacologic treatment (APT) on neurocognitive function in treatment-resistant bipolar disorder depression. Inpatients with DSM-IV-TR-diagnosed, treatment-resistant bipolar depression, who were acutely admitted to 1 of the 7 clinical study centers in Norway, were recruited from May 2008 to April 2011 into a prospective, randomized controlled, 6-week acute treatment trial. General neurocognitive function was assessed with the MATRICS Consensus Cognitive Battery (MCCB), and retrograde memory for autobiographical events was assessed with the Autobiographical Memory Interview-Short Form (AMI-SF) before and shortly after (mean = 23.5 days) a trial with either RUL brief-pulse ECT (mean dose = 233.3 mC) or APT. Seventy-three patients entered, and 39 (nECT = 19, nAPT = 20) completed. Both groups showed improvements in all MCCB domain scores, with no significant differences between the study groups (no interaction effect: F₁,₃₇ = 1.52, P = NS). Improvements in neurocognitive performance were significantly correlated with reductions in depression ratings posttreatment. The AMI-SF score was significantly lower (based on consistent answers from pre- to posttreatment) in the ECT group (72.9%) than in the APT group (80.8%, P = .025), indicating reduced consistency in autobiographical memory after ECT. General neurocognitive function was unaffected by RUL brief-pulse ECT treatment and positively related to improved mood in bipolar depression. Autobiographical memory consistency was reduced in patients treated with ECT. The results suggest that ECT can be used in treatment-resistant bipolar depression without compromising general neurocognitive function. The clinical relevance of reduced autobiographical memory consistency in the ECT group requires further investigation. ClinicalTrials.gov identifier: NCT00664976.

Cognitive functioning in first-episode schizophrenia: MATRICS Consensus Cognitive Battery (MCCB) Profile of Impairment

BackgroundAlthough many studies have assessed cognitive functioning in first-episode schizophrenia (FESz), the pattern and severity of impairment across cognitive domains remain unclear. Moreover, few studies have directly compared the pattern of cognitive performance between FESz and chronic schizophrenia (CSz). In this study we examined the cognitive impairment profile in FESz using a standardized neurocognitive battery (MATRICS Consensus Cognitive Battery; MCCB). MethodsMCCB data were compared from 105 FESz patients, 176 CSz patients and 300 non-psychiatric (NP) participants. Mixed model analysis evaluated group differences in MCCB profiles and relative strengths and weaknesses in the MCCB profiles of patients. Clinical implications of MCCB performance were also examined; we compared the proportion of participants from each group who exhibited clinically-significant global cognitive impairment based on the MCCB Overall Composite score. ResultsFESz and CSz showed impaired performance across all MCCB domains relative to NP. With the exception of relative preservation of working memory and social cognition in FESz, the MCCB domain scores were similar in FESz and CSz. The distribution of impairment on the Overall Composite score did not significantly differ between FESz and CSz; compared to NP, both patient groups were overrepresented in moderate and severe impairment categories. ConclusionThe pattern, magnitude, and distribution of severity of impairment in FESz were similar to that observed in CSz. However, early in the illness, there may be relative sparing of working memory and social cognition.

The MATRICS Consensus Cognitive Battery (MCCB): Clinical and cognitive correlates

The purpose of this study was to examine the cognitive and clinical correlates of the MATRICS Consensus Cognitive Battery (MCCB) which was originally developed to be an endpoint for cognitive enhancement clinical trials. In a sample of 117 people with schizophrenia and 77 healthy control participants we found the following: a) the MCCB was highly sensitive to the type and level of impairment typically observed in schizophrenia, b) the MCCB composite score was highly correlated with WASI Estimated Full Scale IQ score, c) that the MCCB domain scores were generally moderately–highly intercorrelated, d) that MCCB performance was minimally related to clinical symptom type and severity, and e) the MCCB is sensitive to employment status with better performance in employed vs. unemployed patients. These data support the validity of the MCCB as a sensitive measure of cognitive impairment in schizophrenia and suggest that MCCB performance is relevant for functional outcome. The data also suggest that the MCCB domain scores may offer limited resolution on discrete cognitive functions.

A video ethnography approach to assessing the ecological validity of neurocognitive and functional measures in severe mental illness: results from a feasibility study.

The ecological validity of neurocognitive and functional measures in severe mental illness is poorly understood because of a lack of validated research methods to study community life-as-lived. We describe the development of a video ethnography method that measures naturalistic behaviors with codes called community performance indicators (CPIs). The method could provide a strategy to test the ecological validity of neurocognitive and functional assessments. We gathered up to 18.5 hours of video ethnography data on each of 9 subjects with schizophrenia selected for high or low composite scores on the MATRICS Consensus Cognitive Battery (MCCB). We used video ethnography to capture subjects' everyday behaviors in their usual environments. We established 4 CPIs that showed excellent inter-rater and promising test-retest reliability: (1) behavioral activity level, (2) goal pursuit, (3) social interaction, and (4) problem solving. (1) High and low MCCB subjects showed statistically significantly differences on all 4 CPIs. (2) MCCB composite scores were correlated with all 4 CPIs (r = .54 to -.77, P < .01 to .07). (3) The MCCB domain scores demonstrated some specificity in their correlations with the CPIs; eg, verbal learning, reasoning/problem solving, and social cognition were correlated with CPI domains of social interaction and problem solving. We present a method for reliably measuring everyday functional performance in schizophrenia. Results from a small select sample suggest that CPIs capture skills associated with neurocognition, supporting their use in a larger study of ecological validity.