Precision medicine in TBI: Lessons from dopaminergic treatment of cognitive impairment

  • D. Sharp
    Corresponding author.
    Imperial College London, The Computational- Cognitive and Clinical Neuroimaging Laboratory C3NL, London, United Kingdom
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      Developing new treatments for traumatic brain injury (TBI) is challenging. A major difficulty is the heterogeneity of injuries produced. To maximise treatment benefits we need a precision medicine approach. Treatments should be targeted to subsets of patients who share a common biological basis for their post-traumatic impairments. Damage to neuromodulatory neurotransmitter systems are common after TBI, providing a biological basis for on-going cognitive impairment. Defining the extent of this disruption hold the promise guiding targeted treatment. I will discuss this hypothesis in the context of the results of a clinical trial where dopaminergic molecular imaging was used to predict the cognitive effects of methylphenidate. Objectives were to test: 1) whether treatment with methylphenidate improves cognition following TBI; and 2) whether brain dopamine levels predict the magnitude of any improvement in symptoms. 40 moderate-severe TBI patients with persistent cognitive impairments were randomized into a double-blind, placebo controlled, crossover design study. 123I ioflupane SPECT scan (DaTscan), detailed MRI and neuropsychological testing were performed. Dopaminergic abnormalities were common after TBI, most consistently seen in the caudate, and were related to damage in the nigrostriatal system. Methylphenidate did not generally improve cognition. However, patients with low 123I ioflupane SPECT binding showed a significant information processing speed improvements on methylphenidate in contrast to patients with normal scans. The results show that patients 123I ioflupane SPECT scanning predicts response to treatment with methylphenidate after TBI and demonstrates that identifying underlying biological basis for cognitive impairment can facilitate a targeted treatment approach to cognitive enhancement.
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