Traumatic brain injury and the risk of dementia diagnosis: A nationwide cohort study

Abstract

Background: Traumatic brain injury (TBI) has been associated with dementia. The questions of whether the risk of dementia decreases over time after TBI, whether it is similar for different TBI types, and whether it is influenced by familial aggregation are not well studied.

Methods and findings: The cohort considered for inclusion comprised all individuals in Sweden aged ≥50 years on December 31, 2005 (n = 3,329,360). Diagnoses of dementia and TBI were tracked through nationwide databases from 1964 until December 31, 2012. In a first cohort, individuals diagnosed with TBI (n = 164,334) were matched with up to two controls. A second cohort consisted of subjects diagnosed with dementia during follow-up (n = 136,233) matched with up to two controls. A third cohort consisted of 46,970 full sibling pairs with discordant TBI status. During a mean follow-up period of 15.3 (range, 0-49) years, 21,963 individuals in the first cohort (6.3% with TBI, 3.6% without TBI) were diagnosed with dementia (adjusted odds ratio [OR], 1.81; 95% confidence interval [CI], 1.75-1.86). The association was strongest in the first year after TBI (OR, 3.52; 95% CI, 3.23-3.84), but the risk remained significant >30 years (OR, 1.25; 95% CI, 1.11-1.41). Single mild TBI showed a weaker association with dementia (OR, 1.63; 95% CI, 1.57-1.70) than did more severe TBI (OR, 2.06; 95% CI, 1.95-2.19) and multiple TBIs (OR, 2.81; 95% CI, 2.51-3.15). These results were in general confirmed in the nested case-control cohort. TBI was also associated with an increased risk of dementia diagnosis in sibling pairs with discordant TBI status (OR, 1.89; 95% CI, 1.62-2.21). A main limitation of the present study is the observational design. Thus, no causal inferences can be made based on the associations found.

Conclusions: The risk of dementia diagnosis decreased over time after TBI, but it was still evident >30 years after the trauma. The association was stronger for more severe TBI and multiple TBIs, and it persisted after adjustment for familial factors.

Fig 1. The cumulative incidence of dementia diagnosis during follow-up in individuals with and without TBI at baseline (n = 491,252 individuals).

TBI, traumatic brain injury.

Fig 2. The risk of a dementia diagnosis in individuals with only one mild TBI (n = 108,463) and corresponding controls (n = 216,077), during follow-up.

To model the effects, restricted cubic splines with four knots were used (resulting in three degrees of freedom), followed by fitting a proportional hazards model. TBI, traumatic brain injury.

Fig 3. The risk of a dementia diagnosis in individuals with at least one nonmild TBI (n = 39,374) and corresponding controls (n = 77,924), during follow-up.

To model the effects, restricted cubic splines with four knots were used (resulting in three degrees of freedom), followed by fitting a proportional hazards model. TBI, traumatic brain injury.

Fig 4. Associations between TBI and the risk of dementia diagnosis during follow-up in 491,252 individuals.

To model the effects, restricted cubic splines with four knots were used (resulting in three degrees of freedom), followed by fitting a proportional hazards model. TBI, traumatic brain injury.

Fig 5. Associations between TBI and a dementia diagnosis during follow-up in 46,970 sibling pairs discordant for TBI.

To model the effects, restricted cubic splines with four knots were used (resulting in three degrees of freedom), followed by fitting a proportional hazards model. TBI, traumatic brain injury.