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  • COMT Val158Met is Associated with Domain-specific Cognitive Impairment Following Mild Traumatic Brain Injury

    Final Number:

    John K. Yue BA; Ethan A Winkler MD PhD; Thomas W McAllister MD; Nancy Temkin Phd; Adam Ferguson PhD; Hester F. Lingsma MSc; Esther Yuh; Phiroz E. Tarapore MD; Sourabh Sharma; Ava Puccio RN; Kevin Wang PhD; Pratik Mukherjee MD, PhD; Alex B. Valadka MD; David O. Okonkwo MD, PhD; Ramon Diaz-Arrastia MD, PHD; Geoffrey T. Manley MD, PhD

    Study Design:
    Clinical Trial

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2015 Annual Meeting

    Introduction: Mild traumatic brain injury (mTBI) results in variable clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism in catechol-o-methyltransferase (COMT), an enzyme which degrades catecholamine neurotransmitters, may influence cognitive deficits following moderate and/or severe head trauma. However, this has been disputed and its role in mTBI has yet to be studied.

    Methods: A retrospective analysis of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study was conducted to determine whether the COMT Val158Met polymorphism influences outcome on a cognitive battery six months following mTBI – Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), Trail Making Test (TMT) and California Verbal Learning Test (CVLT).

    Results: In 93 predominately Caucasian subjects, we demonstrate that the COMT Met158 allele associates with improved processing speed (mean increase 10.3 points, 95% CI [3.5 to 17.1], p=0.004) and mental flexibility (mean decrease 21.6 seconds [1.4 to 41.8], p=0.037) on WAIS-PSI and TMT, respectively, when compared to Val158/Val158 homozygotes. The association between the COMT Met158 allele and WAIS-PSI persists after controlling for effects of age and years of education (mean increase 8.0 points [1.4 to 14.7], p=0.019). The association between the COMT Met158 allele and TMT completion times demonstrated a statistical trend after controlling for age and education (mean decrease 16.1 seconds [-34.0 to 1.8], p=0.078). Older age and decreased education associate with impairment on WAIS-PSI and TMT independent of COMT. COMT Val158Met did not influence verbal learning on CVLT.

    Conclusions: COMT Val158Met may exert domain-specific cognitive protection following mTBI.

    Patient Care: It will lead to better identification of a subgroup of patients at highest risk for decreased cognitive performance following mild TBI who may benefit from increased clinical surveillance and referral to care.

    Learning Objectives: 1. Identify the incidence and known risk factors of decreased cognitive performance following mild TBI with an emphasis on the COMT Val158Met single nucleotide polymorphism. 2. Describe the importance of a potential underlying relationship between COMT Val158Met and cognitive outcome following mild TBI. 3. Discuss the specific associations between COMT Val158Met and domains of cognitive performance following mild TBI.


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