Virginia Via Research Day Book 2026

Medical Student Research Clinical

03 RELATIONSHIP BETWEEN THE POLYTRAUMA TETRAD AND COGNITIVE IMPAIRMENT AFTER MILD TRAUMATIC BRAIN INJURY

Luke Ignell, MS-III; Marie-Claire Evans, MS-III; Justin Weppner, DO Corresponding author: jlweppner@carilionclinic.org VCOM-Virginia, Blacksburg, Virginia Virginia Tech-Carilion School of Medicine, Roanoke, Virginia Carilion Clinic Brain Injury Center, Roanoke, Virginia Context: Mild traumatic brain injury (mTBI) frequently results in persistent symptoms that can negatively impact cognition and function. We propose the “polytrauma tetrad”—a clinical construct encompassing post-concussion syndrome (PCS), post-traumatic stress disorder (PTSD), chronic pain, and sleep disorders—to better identify high-risk mTBI patients. This study evaluates whether the presence of any or all tetrad components following mTBI increases the risk of developing mild cognitive impairment (MCI) and dementia, compared to mTBI alone. Methods: A retrospective cohort analysis was performed using de-identified electronic health records from the TriNetX Research Network, including adults aged 18–65 diagnosed with mTBI (ICD-10 S06.0) after June 1, 2016. Subjects who developed any tetrad component (PCS, PTSD, chronic pain, or sleep disorders) after mTBI were compared to mTBI-only controls, and those with all four components were compared to those with mTBI alone. Propensity score matching was used to control for age, sex, race, ethnicity, and common comorbidities. Outcomes included diagnosis of MCI at multiple time points and dementia at any time post

injury. Odds ratios (ORs) were calculated using logistic regression. Results: After 1:1 propensity score matching for the all-time post-index event cohorts, the following group sizes and demographics were observed: mTBI+Sleep+ (n = 58,826; mean age 40.4 ± 14.9 years; 33,435 females [56.8%]), mTBI+PCS+ (n = 46,499; mean age 37.6 ± 14.6 years; 27,484 females [59.1%]), mTBI+CP+ (n = 76,853; mean age 38.7 ± 14.8 years; 44,463 females [57.9%]), and mTBI+PTSD+ (n = 102,608; mean age 34.7 ± 13.8 years; 63,739 females [62.1%]). The TBI+Tetrad+ cohort included 4,384 subjects (mean age 45.1 ± 13.6 years; 2,971 females [67.8%]). A diagnosis of any single tetrad component following mTBI was associated with a significantly increased all-time risk of developing MCI and dementia (p < 0.001). The highest all-time odds ratio (OR) for MCI was observed in the PCS group (OR 4.24, 95% CI: 3.75–4.80; absolute risk 2.8%). The ORs for the other components were: PTSD, 1.91 (95% CI: 1.72–2.12); chronic pain, 1.42 (95% CI: 1.28–1.58); and sleep disorders, 1.95 (95% CI: 1.74–2.18). When assessed at multiple time points (6 months, 1 year, 2 years, and 5 years post-injury), the PCS group was the only cohort in which the OR for

MCI decreased over time (p < 0.001), whereas the other three groups showed increasing ORs for MCI over time (p < 0.001). For all-time risk of dementia, the PCS group again had the highest OR at 2.45 (95% CI: 1.81–3.33). In the second phase of analysis, TBI subjects with all tetrad components had a fifteen-fold increase in anytime risk of MCI (3.5%) compared to those with no tetrad components (0.23%) (p < 0.001), and a three-fold increase in anytime risk of dementia (0.85% vs. 0.23%, p < 0.001). Conclusions: Development of PCS, PTSD, chronic pain, or sleep disorders after mTBI substantially increases the risk for MCI and dementia, especially when all tetrad components are present. Early identification and comprehensive, multidisciplinary management of these symptoms are essential to reduce cognitive decline and improve long-term outcomes in mTBI survivors. IRB Statement:This study was determined to be exempt by the Carilion Clinic IRB.

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174 Edward Via College of Osteopathic Medicine (VCOM)