Traumatic brain injuries among veterans and the risk of incident dementia: A systematic review & meta-analysis

Traumatic brain injuries (TBI) among military veterans are increasingly recognized as important causes of both short and long-term neuropsychological dysfunction. However, the association between TBI and the development of dementia is controversial. This systematic review and meta-analysis sought to quantify the risks of all-cause dementia including Alzheimer's diseases and related dementias (ADRD), and to explore whether the relationships are influenced by the severity and recurrence of head injuries.

Database searches of Medline, Embase, Ovid Healthstar, PubMed and PROSPERO were undertaken from inception to December 2020 and supplemented with grey literature searches without language restrictions. Observational cohort studies examining TBI and incident dementia among veterans were analysed using Dersimonian-Laird random-effects models.

Thirteen cohort studies totalling over 7.1 million observations with veterans were included. TBI was associated with an increased risk of all-cause dementia (hazard ratio [HR] = 1.95, 95% confidence interval [CI]: 1.55-2.45), vascular dementia (HR = 2.02, 95% CI: 1.46-2.80), but not Alzheimer's disease (HR = 1.30, 95% CI: 0.88-1.91). Severe and penetrating injuries were associated with a higher risk of all-cause dementia (HR = 3.35, 95% CI: 2.47-4.55) than moderate injuries (HR = 2.82, 95% CI: 1.44-5.52) and mild injuries (HR = 1.91, 95% CI: 1.30-2.80). However, the dose-response relationship was attenuated when additional studies with sufficient data to classify trauma severity were included.

TBI is a significant risk factor for incident all-cause dementia and vascular dementia. These results need to be interpreted cautiously in the presence of significant heterogeneity.