Traumatic brain injury is associated with all-cause dementia but not Alzheimer's dementia in military veterans

Reference

Leung KK, Carr FM, Russell MJ, Bremault-Phillips S, Triscott JAC. Traumatic brain injuries among veterans and the risk of incident dementia: A systematic review & meta-analysis. Age Ageing 2022;51(1):afab194.

Synopsis

These authors searched multiple databases and the grey literature to identify cohort studies that assessed traumatic brain injuries (TBIs) and the subsequent development of all-cause dementia or Alzheimer’s disease and related dementias (ADRD) in military veterans. Two authors independently evaluated studies for inclusion — and, in the sole instance of disagreement, used discussion with a third author to resolve it. Ultimately, they identified 13 studies with more than 7.1 million observations. Approximately 395,000 veterans had sustained at least one TBI. Twelve of the studies were used for meta-analysis for all-cause dementia and 5 for ADRD. The authors report several potential sources of heterogeneity: different wars with different potential toxin exposures; patients from different countries; sample sizes from 22 to more than 4 million; study durations from 1 year to 53 years; and 4 studies followed the veterans from the time of injury forward (range = 30 to 53 years) while the rest of the studies enrolled veterans after the injury and were much shorter (1 to 14 years). Overall, the studies were of moderate to high quality, and all used reasonable methods for ascertaining the development of dementia or ADRD. Among the 12 cohort studies that evaluated incident all-cause dementia, all but 4 found an association with TBI (pooled hazard ratio [HR] = 1.95; 95% CI 1.55 - 2.45); however, the authors identified marked heterogeneity among the data (I2 = 96.2%; P < .01). The association between TBI and incident dementia persisted after multiple subgroup and sensitivity analyses. The 5 studies that evaluated ADRD, however, found no significant relationship between TBI and subsequent ADRD. In the few studies that assessed other types of dementia, TBI was associated with an increased risk of developing vascular dementia (HR = 2.02; 1.46 - 2.80; I2 = 18.1%; P = .3) and one study reported an increased risk of a composite outcome of vascular, alcohol, and unspecified dementia. The authors also did multiple subgroup analyses to identify sources of heterogeneity, the most interesting of which were the higher risk when the TBI occurred during active duty (HR = 3.44; 3.33 - 3.57) and the lack of association between self-reported TBI and dementia (HR = 1.15; 0.79 - 1.68).