Event Date
Early-Onset Depression After Traumatic Brain Injury as a Potential Prodromal Marker of Dementia in 172,074 Civilians
Miriam Nuño
Professor, Biostatistics
Background and Objectives: To estimate the incidence of depression and dementia following traumatic brain injury (TBI) and to examine whether incident post-TBI depression is associated with subsequent dementia, consistent with a potential prodromal role.
Methods: We conducted a retrospective cohort study of 172,074 U.S. adults aged ≥55 years with TBI (2000–2022). Depression and dementia were identified using ICD-9/10 codes, with depression additionally defined by antidepressant use. Cox proportional hazards models using age as the time scale estimated associations between incident depression and dementia risk.
Results: During a mean follow-up of 3.4 years, 24.8% of participants developed depression and 12.3% developed dementia. Incident depression was associated with increased dementia risk compared with no depression (hazard ratio [HR], 1.29; 95% CI, 1.25–1.32), with the strongest association observed after mild TBI (HR, 1.41; 95% CI, 1.33–1.47). Dementia risk was highest among individuals with both a depression diagnosis and antidepressant treatment (HR, 1.48; 95% CI, 1.44–1.53). Depression occurring within one month of TBI was associated with substantially greater dementia risk than later-onset depression (HR, 2.33; 95% CI, 2.20–2.50). Dementia-free survival declined progressively with earlier depression onset.
Conclusion: Depression following TBI was associated with an increased risk of subsequent dementia, particularly after mild injury. Earlier depression onset after TBI was associated with greater dementia risk, consistent with depression as a potential early clinical marker of neurodegenerative disease and underscoring the importance of timely mental health assessment after TBI.
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