Association of COMT Val¹⁵⁸Met Polymorphism With Delirium Risk and Outcomes After Traumatic Brain Injury

Abstract

The authors investigated the association of the catechol-O-methyltransferase (COMT) gene Val 158 Met polymorphism with delirium risk and functional and cognitive outcomes among patients with complicated mild to moderate traumatic brain injury (TBI). Methods:In a prospective observational cohort study, patients were monitored for occurrence of delirium during the first 4 days of admission by using the Confusion Assessment Method. Functional and cognitive outcomes were evaluated with the Glasgow Outcome on Discharge Scale and the Montreal Cognitive Assessment test, respectively. Eightynine patients were included in the study; of these, 17 (19%) were diagnosed with delirium. Results:The COMT Val 158 /Val 158 polymorphism was associated with increased risk of delirium in multivariable regression analyses adjusted for alcohol misuse, history of neurological disorder, age, and admission Glasgow Coma Scale score (odds ratio=4.57, 95% CI=1.11, 18.9, p=0.036).The COMT Met 158 allele was associated with better functional outcomes in univariate analysis (odds ratio=2.82, 95% CI=1.10, 7.27, p=0.031) but not in multivariable analysis (odds ratio=2.33, 95% CI=0.89, 6.12, p=0.085). Cognitive outcomes were not associated with the COMT Val 158 Met polymorphism in univariate regression analysis (p=0.390). Delirium was a significant predictor of worse functional and cognitive outcomes in multivariable regression analyses adjusted for other risk factors (odds ratio=0.04, 95% CI= 0.01, 0.16, p,0.001, and b=-3.889, 95% CI=-7.55, -0.23, p= 0.038, respectively). Conclusions:The COMT genotype is important in delirium risk and functional outcomes of patients with mild to moderate TBI. Whether the COMT genotype is associated with outcomes through incident delirium remains to be determined in larger studies.

Predisposing and Precipitating Factors Associated With Delirium

“…Reasons for exclusion were no diagnosis by physician or research personnel (428 studies), no characterization of predisposing or precipitating factors (338 studies), retrospective study design (86 studies), not diagnosed by reference standard (108 studies), no multivariable model (43 studies), delirium assessment not conducted in person (25 studies), not cohort or case-control design (20 studies), sample included less than 50 patients (12 studies), abstract only (18 studies), cohort previously reported (3 studies), and pediatric population (1 studies). Ultimately, 315 studies…”

“…Delirium was measured by research personnel in 171 studies (54.3%), a combination of research personnel and physicians in 5 studies (1.6%), and a physician in 139 studies …”

“…The most frequently used assessment tool was the CAM, which was used in 174 studies (55.2%). Delirium was assessed daily or more frequently in 222 studies…”

“…We conducted a systematic review of the literature to identify predisposing and precipitating factors associated with delirium. Across 315 included studies…”

First delirium episode in Parkinson’s disease and parkinsonism: incidence, predictors, and outcomes

“…It is possible this study was underpowered to find a weak association. Analysis of the COMT Val 158 Met polymorphism and its association with delirium would be useful to extend this work as this has previously been associated with delirium after head injury 23 although it has been reported to have no association with dementia in PD 24 .…”