Association of traumatic brain injury with subsequent neurological and psychiatric disease: A meta-analysis

David C. Perry, Virginia E. Sturm, Matthew J. Peterson, Carl F. Pieper, Thomas Bullock, Bradley F. Boeve, Bruce L. Miller, Kevin M. Guskiewicz, Mitchel S. Berger, Joel H. Kramer, Kathleen A. Welsh-Bohmer

Research output: Contribution to journalReview articlepeer-review

148 Scopus citations


OBJECTIVE: Mild traumatic brain injury (TBI) has been proposed as a risk factor for the development of Alzheimer’s disease, Parkinson’s disease, depression, and other illnesses. This study’s objective was to determine the association of prior mild TBI with the subsequent diagnosis (that is, at least 1 year postinjury) of neurological or psychiatric disease. METHODS: All studies from January 1995 to February 2012 reporting TBI as a risk factor for diagnoses of interest were identified by searching PubMed, study references, and review articles. Reviewers abstracted the data and assessed study designs and characteristics. RESULTS: Fifty-seven studies met the inclusion criteria. A random effects meta-analysis revealed a significant association of prior TBI with subsequent neurological and psychiatric diagnoses. The pooled odds ratio (OR) for the development of any illness subsequent to prior TBI was 1.67 (95% CI 1.44–1.93, p < 0.0001). Prior TBI was independently associated with both neurological (OR 1.55, 95% CI 1.31–1.83, p < 0.0001) and psychiatric (OR 2.00, 95% CI 1.50–2.66, p < 0.0001) outcomes. Analyses of individual diagnoses revealed higher odds of Alzheimer’s disease, Parkinson’s disease, mild cognitive impairment, depression, mixed affective disorders, and bipolar disorder in individuals with previous TBI as compared to those without TBI. This association was present when examining only studies of mild TBI and when considering the influence of study design and characteristics. Analysis of a subset of studies demonstrated no evidence that multiple TBIs were associated with higher odds of disease than a single TBI. CONCLUSIONS: History of TBI, including mild TBI, is associated with the development of neurological and psychiatric illness. This finding indicates that either TBI is a risk factor for heterogeneous pathological processes or that TBI may contribute to a common pathological mechanism.

Original languageEnglish (US)
Pages (from-to)511-526
Number of pages16
JournalJournal of neurosurgery
Issue number2
StatePublished - 2016


  • Dementia
  • Head injury
  • Meta-analysis
  • Psychiatry
  • Traumatic brain injury

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology


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