• Jesse R Fann, Anette Riisgaard Ribe, Henrik Schou Pedersen, Morten Fenger-Grøn, Jakob Christensen, Michael Eriksen Benros, and Mogens Vestergaard.
• Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA. Electronic address: fann@uw.edu.
• Lancet Psychiatry. 2018 May 1; 5 (5): 424-431.

BackgroundTraumatic brain injury (TBI) has been associated with increased risk of dementia; however, large-scale studies with long follow-up have been scarce. We investigated the association between TBI, including severity and number of TBIs, and the subsequent long-term risk of dementia.MethodsWe did a nationwide population-based observational cohort study in Denmark using information on citizens from national registries. We used the Danish Civil Registration System to establish a population-based cohort consisting of all people born in Denmark who were living in the country on Jan 1, 1995, and who were at least 50 years old at some point during follow-up (between 1999 and 2013). We obtained information on TBIs from the Danish National Patient Register (NPR), and obtained information on dementia by combining data recorded in the NPR, the Danish Psychiatric Central Register, and the Danish National Prescription Registry (DNPR). The long-term risk of dementia after TBI was established using survival analysis. We used three prespecified models for each of the three analyses: different time periods since the TBI, multiple TBIs, and sex. The first model adjusted for sociodemographic factors, the second model added medical and neurological comorbidities, and the third added psychiatric comorbidities.FindingsWe used data from a cohort of 2 794 852 people for a total of 27 632 020 person-years (mean 9·89 years per patient) at risk of dementia. 132 093 individuals (4·7%) had at least one TBI during 1977-2013, and 126 734 (4·5%) had incident dementia during 1999-2013. The fully adjusted risk of all-cause dementia in people with a history of TBI was higher (hazard ratio [HR] 1·24, 95% CI 1·21-1·27) than in those without a history of TBI, as was the specific risk of Alzheimer's disease (1·16, 1·12-1·22). The risk of dementia was highest in the first 6 months after TBI (HR 4·06, 3·79-4·34) and also increased with increasing number of events (1·22, 1·19-1·25 with one TBI to 2·83, 2·14-3·75 with five or more TBIs). Furthermore, TBI was associated with a higher risk of dementia (1·29, 1·26-1·33) in people with TBI than in individuals with a non-TBI fracture not involving the skull or spine. The younger a person was when sustaining a TBI, the higher the HRs for dementia when stratified by time since TBI.InterpretationTBI was associated with an increased risk of dementia both compared with people without a history of TBI and with people with non-TBI trauma. Greater efforts to prevent TBI and identify strategies to ameliorate the risk and impact of subsequent dementia are needed.FundingLundbeck Foundation.Copyright © 2018 Elsevier Ltd. All rights reserved.

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