A – 123 TBI and Dementia Among Veterans Receiving Care within the VA Healthcare System: Identification of Unique Risk Profiles for Male and Female Veterans

Abstract Objective Traumatic brain injury (TBI) has been identified as a risk factor for Alzheimer’s disease (AD) and AD-related dementias (ADRD), but little is known about whether this association differs by sex. We conducted sex-stratified analyses to better understand the relationship between TBI history and ADRD among male and female Veterans receiving VA care. Method We included VA-enrolled Veterans with a TBI diagnosis between 1999-2022 and a matched comparison group of Veterans without TBI. We used International Classification of Diseases (ICD) codes from VA electronic health records (EHR) to determine TBI history and severity and to identify ADRD cases and controls. Veterans were excluded if ADRD preceded TBI or if age at disease onset was < 65. Results Among 289,024 Veterans evaluated (n=13,271 women), 33.3% had a TBI history (age: M=65.2 years; 4.3% women) and 12.2% had ADRD (age: M=71.5 years; 2.0% women). Adjusting for age at TBI, age at ADRD, race, and ethnicity, TBI was significantly associated with increased risk for ADRD in both female and male Veterans: female mild TBI (mTBI) OR=1.71 (95% CI: 1.34-2.17); female moderate/severe/penetrating TBI (mspTBI) OR=2.93 (2.31-3.71); male mTBI OR=2.03 (1.96-2.10); and male mspTBI OR=2.32 (2.24-2.39). Conclusion Examining associations between TBI and ADRD using sex-stratified models revealed unique risk profiles for males and females, with female Veterans with mspTBI history showing the greatest risk for ADRD and female Veterans with mTBI history showing the lowest risk. Future studies will expand upon these findings by exploring additional EHR-derived risk factors using sex-stratified modeling to better understand ADRD risk profiles in VA-enrolled Veterans.