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1 April 2021

CANTAB and CENTRE-TBI – 10 years working together

CENTRE-TBI recently concluded their 10 year study into the relationship between cognition and function in daily life after traumatic brain injury. We caught up with Prof Lindsay Wilson to hear the key findings from this worldwide study.

Can you tell us more about your research group?

European researchers and international colleagues received support from The Framework 7 Program of The European Union in 2013 for CENTER-TBI (Collaborative European Neurotrauma Effectiveness Research: www.center-tbi.eu; Maas et al, 2015).  CENTER-TBI is part of the International Initiative on Traumatic Brain Injury Research (InTBIR; https://intbir.nih.gov/), a collaboration of funding agencies with current projects in Europe, the USA and Canada.

What is the rationale behind your study?

CENTER-TBI aims to develop precision medicine approaches by improving characterization and classification of traumatic brain injury (TBI), and to utilize comparative effectiveness research, to identify the most effective clinical care, providing high quality evidence in support of treatment recommendations and guidelines. CENTER-TBI includes patients with TBI from 20 countries in Europe and Israel, with more recent contributions from Australia, China and India.

A key component of the CENTER-TBI study was the collection of high quality outcome data. Outcome in TBI is usually characterized using the Glasgow Outcome Score- Extended (GOSE), which characterizes patients on an eight level functional outcome scale, which ranges from complete recovery (GOSE 8) to death (GOSE 1).  In CENTER-TBI we wished to obtain more detailed characterization of patient outcomes, and hence also administered a range of instruments assessing quality of life, mental health, and cognition. 

Which methods did you use?

Quality of life and mental health were assessed using self-report questionnaires. In those patients where cognitive testing was possible, we administered a combination of classic paper and pencil tests (RAVLT and TMT) in order to allow cross comparisons with other InTBIR studies, and more detailed assessment of multiple cognitive domains using CANTAB. We selected Paired Associates Learning (PAL), Reaction Time (RTI), Rapid Visual Information Processing (RVP), Multitasking Test (previously AST), Spatial Working Memory (SWM), and Stockings of Cambridge (SOC) as they have been shown to be particularly sensitive to cognitive impairment in TBI. Over 1500 patients with traumatic brain injury had cognitive assessment at 6 months post-injury.

What are your key findings?

The initial results of our analyses of cognitive data have been very interesting, (Wilson et al, 2021) showing that cognitive deficits are pervasive following TBI (even in those patients who appear to have made good recoveries). Measures of processing speed show the strongest association with functional outcome. However, even more intriguingly, the most rapid decline in cognitive function is seen in patients with moderate disability – suggesting that these deficits may substantially contribute to functional deficits and societal reintegration.

What are the implications of your study?

If these findings are confirmed in future studies, we may be able to identify patients who show substantial disability in whom the underlying mechanisms are cognitive – such patients may be candidates for therapy with cognitive enhancers.

Why did you choose CANTAB?

We chose CANTAB because of the fact that it was language neutral (we were operating in 20 European countries) and members of the CENTER-TBI Consortium had substantial past experience with using the platform in the assessment of TBI patients, both in the acute context and at follow up.

What are the next steps for your research?

We are also using the cognitive data to relate to structural and functional imaging – analyses which will characterize the neuroanatomical substrates of these deficits in TBI. Furthermore, we are seeking genetic associations for either individual deficits or for summary measures derived by principal component analysis – these results may inform our understanding of the underlying neurobiology of TBI.

References 

1. Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, Bragge P, Brazinova A, Büki A, Chesnut RM, Citerio G, Coburn M, Cooper DJ, Crowder AT, Czeiter E, Czosnyka M, Diaz-Arrastia R, Dreier JP, Duhaime AC, Ercole A, van Essen TA, Feigin VL, Gao G, Giacino J, Gonzalez-Lara LE, Gruen RL, Gupta D, Hartings JA, Hill S, Jiang JY, Ketharanathan N, Kompanje EJO, Lanyon L, Laureys S, Lecky F, Levin H, Lingsma HF, Maegele M, Majdan M, Manley G, Marsteller J, Mascia L, McFadyen C, Mondello S, Newcombe V, Palotie A, Parizel PM, Peul W, Piercy J, Polinder S, Puybasset L, Rasmussen TE, Rossaint R, Smielewski P, Söderberg J, Stanworth SJ, Stein MB, von Steinbüchel N, Stewart W, Steyerberg EW, Stocchetti N, Synnot A, Te Ao B, Tenovuo O, Theadom A, Tibboel D, Videtta W, Wang KKW, Williams WH, Wilson L, Yaffe K; InTBIR Participants and Investigators. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017 Dec;16(12):987-1048. doi: 10.1016/S1474-4422(17)30371-X. Epub 2017 Nov 6. PMID: 29122524.

2. Maas AI, Menon DK, Steyerberg EW, Citerio G, Lecky F, Manley GT, Hill S, Legrand V, Sorgner A; CENTER-TBI Participants and Investigators. Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI): a prospective longitudinal observational study. Neurosurgery. 2015 Jan;76(1):67-80. doi: 10.1227/NEU.0000000000000575. PMID: 25525693.

3.Wilson L, Horton L, Kunzmann K, Sahakian BJ, Newcombe VF, Stamatakis EA, von Steinbuechel N, Cunitz K, Covic A, Maas A, Van Praag D, Menon D; CENTER-TBI participants and investigators. Understanding the relationship between cognitive performance and function in daily life after traumatic brain injury. J Neurol Neurosurg Psychiatry. 2020 Dec 2:jnnp-2020-324492. doi: 10.1136/jnnp-2020-324492. Epub ahead of print. PMID: 33268472.

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Author:

Prof. Lindsay Wilson

Professor of Psychology, University of Stirling, UK on behalf of CENTER-TBI

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