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, 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

Abstract

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.

Keywords: ALS = amyotrophic lateral sclerosis; CI = confidence interval; CTE = chronic traumatic encephalopathy; LOC = loss of consciousness; OR = odds ratio; TBI = traumatic brain injury; dementia; head injury; meta-analysis; psychiatry; traumatic brain injury.

Figures

Figure 1
Figure 1
Flow chart depicting study identification and screening
Figure 2
Figure 2
Individual and pooled odds ratios for all included studies (to be aligned with Table 1).
Figure 3
Figure 3
Publication bias analysis. (A) Funnel plot of OR versus total sample size. (B) Funnel plot of OR versus total sample size after excluding the three studies with largest sample sizes (Rugbjerg 2008, Nielson 2001, and Turner 2010). (C) Plot of the logarithm of the OR after excluding the three largest sample size studies compared to the standard error of the logarithm of the OR showing a regression line and 95% confidence interval with slope that is not statistically significantly different from 0.

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