Delirium in Patients With Traumatic Brain Injury and Long‐Term Cognitive Decline: A Global Federated Real World Data Analysis

ABSTRACT Background and Objective Delirium may occur in patients with traumatic brain injury (TBI), but this may be a marker for subsequent cognitive decline post‐TBI. We aimed to compare cognitive outcomes and all‐cause mortality between TBI patients with and without delirium. Methods We conducted a retrospective cohort study using the TriNetX global federated research network. We compared TBI patients who developed delirium within 14 days of TBI diagnosis with those who did not. The primary outcome was the 2‐year composite risk of dementia, vascular dementia and Alzheimer's disease. Secondary outcomes included dementia, vascular dementia, Alzheimer's disease and all‐cause mortality. Pre‐specified subgroup analyses were performed in female patients, older adults (≥ 75 years), and individuals with substance use. Results TBI patients with delirium ( n  = 2564; mean age, 66.6 ± 19.4 years; 59.4% male), when compared with TBI patients without delirium ( n  = 667,950; mean age, 48.0 ± 25.1 years; 60.3% male), had more baseline comorbidities, including psychiatric disease, cerebrovascular disease and ischemic heart disease. After propensity score matching, TBI patients with delirium, compared with those without delirium, had a higher 2‐year risk of the primary composite outcome (HR, 2.47; 95% CI, 1.84–3.31), as well as dementia (HR, 2.63; 95% CI, 1.92–3.60), vascular dementia (HR, 2.76; 95% CI, 1.45–5.24) and Alzheimer's disease (HR, 2.23; 95% CI, 1.21–4.09). Conclusion Delirium following TBI is associated with an increased risk of dementia and Alzheimer's disease. Delirium post‐TBI may be a marker or a contributing factor to long‐term cognitive decline in TBI patients.