Abstract
IMPORTANCE: Traumatic brain injury (TBI) has been associated with mortality and chronic conditions, including dementia. However, research is limited regarding the disease process by which TBI leads to long-term mortality. OBJECTIVE: To assess TBI incidence over decades and its association with long-term all-cause and dementia-related mortality among participants in the Framingham Heart Study (FHS), with the hypothesis that the association would be largely attributable to dementia-related mortality. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the original and offspring cohorts of the FHS, a multigenerational, community-based cohort study conducted from 1948 to 2022. Participants with TBI were matched 1:3 to unexposed participants based on birth year, sex, and generational cohort. TBI data were collected from comprehensive medical record review and study examination visit records from the time of enrollment until death or conclusion of data collection. Data analysis was performed from February 1, 2023, to November 1, 2024. EXPOSURE: Traumatic brain injury. MAIN OUTCOMES AND MEASURES: The primary outcomes assessed were all-cause and dementia-related mortality. Time-to-event analyses were conducted using data from the FHS original and offspring cohorts. RESULTS: This study included 10 333 FHS participants: 5209 from the original cohort (mean [SD] age at enrollment, 44 [9] years; 55.2% female; mean follow-up, 35 [15] years) and 5124 from the offspring cohort (mean [SD] age at enrollment, 36 [11] years; 51.5% female; mean follow-up, 39 [11] years). A total of 886 participants (17.0%) in the original cohort and 1243 (24.3%) in the offspring cohort experienced at least 1 TBI, with incidence rates of 7.02 (95% CI, 6.63-7.40) and 9.11 (95% CI, 8.70-9.51) TBI events per 1000 person-years and a mean (SD) age at TBI of 74 (16) and 71 (15) years, respectively. Falls were the most common mechanism of TBI in both the original (65.4%) and offspring (82.8%) cohorts. TBI was associated with all-cause mortality (hazard ratio [HR], 1.15 [95% CI, 1.06-1.26]) in a dose-dependent fashion with TBI severity (mild: HR, 1.06 [95% CI, 0.96-1.16]; moderate to severe: HR, 1.82 [95% CI, 1.48-2.25]). TBI was also associated with dementia-related mortality in a dose-dependent fashion (mild TBI: HR, 1.60 [95% CI, 1.31-1.97]; moderate to severe TBI: HR, 3.67 [95% CI, 2.31-5.80]) but not with non-dementia-related mortality. CONCLUSIONS AND RELEVANCE: In this study of FHS community-based original and offspring cohorts followed up over 7 decades, most TBIs occurred late in life and were related to falls. TBI was associated with an increased risk of long-term, all-cause mortality in a dose-dependent fashion, with dementia-related mortality largely contributing to this association. Preventing falls to reduce TBI could have important implications for dementia and mortality.