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Region Hovedstaden - en del af Københavns Universitetshospital

Effekt af Action-Based Cognitive remediation på kognitiv funktion og frontallapsaktivitet hos patienter med bipolar lidelse i remission og raske familiært disponerende personer med kognitive vanskeligheder (PRETEC-ABC)

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Prefrontal Target Engagement as a biomarker model for Cognitive improvement: Action-Based Cognitive Remediation trial (2016-2020). Psychiatric disorders are often accompanied by cognitive impairment but there is a lack of treatments with solid and lasting efficacy on cognition. A rapid, cost-efficient biomarker is therefore critically needed to select among new candidate treatments prior to large-scale clinical efficacy trials. This part of the PRETEC Marker project funded by a 5-year Lundbeck Foundation Fellowship, investigated the effects of Action-Based Cognitive Remediation (ABCR) in 61 patients with bipolar disorder.

Randomised controlled intervention study investigating the effects of 10 weeks of bi-weekly ABCR vs. unstructured group sessions. Participants were assessed for neuropsychological function, mood symptoms, psychosocial functions 4 times (baseline, after 2 weeks of treatment, after treatment completion and 6 months follow-up) and with fMRI at baseline and after 2 weeks of treatment.

Resultater (forventede):
The randomised controlled trial revealed no significant effect of ABCR on the primary outcome, a cognitive composite score. However, there was a significant and large effect on the secondary cognitive outcome, a measure of executive function, and some tertiary outcomes including verbal memory. The improvement in executive function was accompanied by an early increase in the dorsal prefrontal cortex response during working memory after only two weeks of treatment, an effect that predicted subsequent improvement of executive function.
These findings have so far been published in 3 papers:
1. Ott CV, Macoveanu J, Bowie CR, Fisher PM, Knudsen GM, Kessing LV, Miskowiak KW. Change in prefrontal activity and executive functions after action-based cognitive remediation in bipolar disorder: a randomized controlled trial. Neuropsychopharmacology. 2020 Nov 9. doi: 10.1038/s41386-020-00901-7. Online ahead of print. PMID: 33168945
2. Ott CV, Vinberg M, Kessing LV, Bowie CR, Forman JL, Miskowiak KW. Effect of Action-Based Cognitive Remediation on cognitive impairment in patients with remitted bipolar disorder: A randomized controlled trial. Bipolar Disord. 2020 Oct 14. doi: 10.1111/bdi.13021. PMID: 33053258
3. Ott CV, Vinberg M, Bowie CR, Christensen EM, Knudsen GM, Kessing LV, Miskowiak KW. Effect of action-based cognitive remediation on cognition and neural activity in bipolar disorder: study protocol for a randomized controlled trial. Trials. 2018 Sep 12;19(1):487. doi: 10.1186/s13063-018-2860-8.

One additional paper on the neuronal underpinnings of verbal memory improvements is currently in prep.

Diskussion/Impact (forventet):
Action-Based Cognitive Remediation seems to be particularly relevant for improvement of executive function and is accompanied by early increase in the dorsal prefrontal cortex response. Implementation of fMRI to investigate neurocircuitry target engagement is a promising approach to screen for pro-cognitive efficacy in treatment development strategies targeting cognitive impairments.
Together with the PRETEC-EPO study, the findings will clarify whether prefrontal cortex activity increase is a novel neurocircuitry-based biomarker model for pro-cognitive effects which can be implemented for go/no-go decisions in treatment development. This could lead to a break-through in development of treatment for cognitive impairment in neuropsychiatric disorders.


  • Sundhedsvidenskab - Mood Disorders, Neuroimaging, Biomarkers, Psychotherapy, Psychological assessment and psychometrics, Cognition, Randomized Controlled Clinical Trial

ID: 61736782