Developing Cognition Endpoints for the CENTER-TBI Neuropsychological Test Battery

Abstract

Background: Measuring cognitive functioning is common in traumatic brain injury (TBI) research, but no universally accepted method for combining several neuropsychological test scores into composite, or summary, scores exists. This study examined several possible composite scores for the test battery used in the large-scale study Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Methods: Participants with mild traumatic brain injury (MTBI; n = 140), orthopedic trauma (n = 72), and healthy community controls (n = 70) from the Trondheim MTBI follow-up study completed the CENTER-TBI test battery at 2 weeks after injury, which includes both traditional paper-and-pencil tests and tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Seven composite scores were calculated for the paper and pencil tests, the CANTAB tests, and all tests combined (i.e., 21 composites): the overall test battery mean (OTBM); global deficit score (GDS); neuropsychological deficit score-weighted (NDS-W); low score composite (LSC); and the number of scores ≤5th percentile, ≤16th percentile, or <50th percentile. Results: The OTBM and the number of scores <50th percentile composites had distributional characteristics approaching a normal distribution. The other composites were in general highly skewed and zero-inflated. When the MTBI group, the trauma control group, and the community control group were compared, effect sizes were negligible to small for all composites. Subgroups with vs. without loss of consciousness at the time of injury did not differ on the composite scores and neither did subgroups with complicated vs. uncomplicated MTBIs. Intercorrelations were high within the paper-and-pencil composites, the CANTAB composites, and the combined composites and lower between the paper-and-pencil composites and the CANTAB composites. Conclusion: None of the composites revealed significant differences between participants with MTBI and the two control groups. Some of the composite scores Stenberg et al. Cognition Endpoints were highly correlated and may be redundant. Additional research on patients with moderate to severe TBIs is needed to determine which scores are most appropriate for TBI clinical trials.

Examining Test-Retest Reliability and Reliable Change for Cognition Endpoints for the CENTER-TBI Neuropsychological Test Battery

“…The Neuropsychological Deficit Score-Weighted (NDS-W) is a new composite calculated in previous cognition endpoint research only (7)(8)(9). It assigns the following weights to T scores: ≥50 = 0, 49-47 = 0.25, 46-44 = 0.5, 43-41 = 1, 40-37 = 1.5, 36-35 = 2, 34-31 = 3, 30-28 = 4, 27-24 = 5, 23-21 = 6, and ≤20 = 7.…”

“…The Low Score Composite (LSC) is a new composite calculated in previous cognition endpoint research only (7)(8)(9). T scores of 50 or higher are assigned a weight of 50, and T scores below 50 are assigned a weight that equals the T score (i.e., a T score of 40 would equal a weight of 40).…”

“…Given that cognition is multifaceted and it is commonly measured with a variety of tests that index different cognitive domains, it would be useful to create a single composite score, or cognition endpoint, for TBI research and clinical trials (6). Our research team has recently examined seven candidate composite scores, derived from prior studies (7,8), using the neuropsychological test battery from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) (9). CENTER-TBI is a large-scale, multi-national, observational study that aspires to identify best practices, develop precision medicine, and improve outcomes for people with TBIs via comparative-effectiveness studies (10)(11)(12).…”

“…CENTER-TBI is a large-scale, multi-national, observational study that aspires to identify best practices, develop precision medicine, and improve outcomes for people with TBIs via comparative-effectiveness studies (10)(11)(12). In our prior study on the CENTER-TBI neuropsychological battery, data from the Trondheim MTBI follow-up study, in which the CENTER-TBI neuropsychological battery was administered, was used to calculate the composite scores separately for four traditional paper-and-pencil tests, five computerized neuropsychological tests, and a combined battery of all nine tests (9). Before determining which candidate composite score(s) might be most useful for clinical research in TBI, and with the CENTER-TBI battery in particular, it is important to examine these scores longitudinally for stability (in people without TBI) and sensitivity to change (in people with TBI).…”

“…A composite score with high test-retest reliability that is sensitive to changes in cognitive functioning coinciding with the natural history of TBI recovery is desirable in TBI research and clinical trials that use rate of change as the primary endpoint. The purpose of this descriptive study is to compare and contrast the test-retest reliabilities, and estimates of reliable change, for the seven candidate composite scores that have been recently applied to the CENTER-TBI battery (9) in patients with mild TBI, in trauma controls without head injury, and in healthy community controls.…”