Associations between Traumatic Brain Injury, Medical Comorbidities, and Alzheimer’s Disease and Related Dementias Using VA Electronic Health Record Data

Abstract Objective The relationship between traumatic brain injury (TBI) and Alzheimer’s disease and related dementias (ADRD) is complex, nuanced, and likely influenced by a multitude of factors. The purpose of this study was to better understand associations between TBI and ADRD in the context of other medical comorbidities. Method Participants included Veterans receiving VA care with a TBI diagnosis between 1999–2022, and a comparison group of Veterans without TBI. All medical conditions (TBI, ADRD, and other medical comorbidities) were collected using International Classification of Diseases codes from VA electronic health records. We excluded Veterans with an ADRD diagnosis prior to age 65 or preceding TBI. The association of ADRD with TBI severity and other comorbidities was examined using logistic regression adjusting for age at TBI, age at ADRD, sex, race, and ethnicity. Results The sample included 289,024 Veterans (95.4% male); 96,539 (33.3%) had TBI (age TBI: M = 65.2, SD = 10.4; 12.8% mild-TBI, 12.6% moderate/severe/penetrating-TBI, 7.9% unclassified-TBI) and 35,270 (12.2%) had ADRD (age ADRD: M = 71.5, SD = 7.8). TBI was significantly associated with increased odds for ADRD with a dose effect by severity: mild-TBI OR = 2.02 (95% CI: 1.95–2.09); moderate/severe/penetrating-TBI OR = 2.33 (2.26–2.41). When adjusting for other comorbidities, TBI remained significantly associated with ADRD: mild-TBI OR = 1.53 (1.45–1.56); moderate/severe/penetrating-TBI OR = 1.55 (1.49–1.60). Conclusion TBI history was associated with increased odds of developing ADRD. When controlling for comorbidities, the association between TBI and ADRD was attenuated, highlighting the importance of multidisciplinary approaches to ADRD intervention. Findings are being leveraged to develop an ADRD risk score tool to improve detection of Veterans most at risk for ADRD.