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      Is traumatic brain injury a risk factor for neurodegeneration? A meta-analysis of population-based studies

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          Abstract

          Background

          To determine the association of prior traumatic brain injury (TBI) with subsequent diagnosis of neurodegeneration disease.

          Methods

          All studies from 1980 to 2016 reporting TBI as a risk factor for diagnoses of interest were identified by searching PubMed, Embase, study references, and review articles. The data and study design were assessed by 2 investigators independently. A meta-analysis was performed by RevMan 5.3.

          Results

          There were 18 studies comprising 3,263,207 patients. Meta-analysis revealed a significant association of prior TBI with subsequent dementia. The pooled odds ratio (OR) for TBI on development of dementia, FTD and TDP-43 associated disease were 1.93 (95% CI 1.47–2.55, p < 0.001), 4.44 (95% CI 3.86–5.10, p < 0.001), and 2.97 (95% CI 1.35–6.53, p < 0.001). However, analyses of individual diagnoses found no evidence that the risk of Alzheimer’s disease, and Parkinson’s disease in individuals with previous TBI compared to those without TBI.

          Conclusions

          History of TBI is not associated with the development of subsequent neurodegeneration disease. Care must be taken in extrapolating from these results because no suitable criteria define post TBI neurodegenerative processes. Therefore, further research in this area is needed to confirm these questions and uncover the link between TBI and neurodegeneration disease.

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          Most cited references26

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          Head injury as a risk factor for Alzheimer's disease: the evidence 10 years on; a partial replication.

          To determine, using a systematic review of case-control studies, whether head injury is a significant risk factor for Alzheimer's disease. We sought to replicate the findings of the meta-analysis of Mortimer et al (1991). A predefined inclusion criterion specified case-control studies eligible for inclusion. A comprehensive and systematic search of various electronic databases, up to August 2001, was undertaken. Two independent reviewers screened studies for eligibility. Fifteen case-control studies were identified that met the inclusion criteria, of which seven postdated the study of Mortimer et al. We partially replicated the results of Mortimer et al. The meta-analysis of the seven studies conducted since 1991 did not reach significance. However, analysis of all 15 case-control studies was significant (OR 1.58, 95% CI 1.21 to 2.06), indicating an excess history of head injury in those with Alzheimer's disease. The finding of Mortimer et al that head injury is a risk factor for Alzheimer's disease only in males was replicated. The excess risk of head injury in those with Alzheimer's disease is only found in males (males: OR 2.29, 95% CI 1.47 to 2.06; females: OR 0.91, 95% CI 0.56 to 1.47). This study provides support for an association between a history of previous head injury and the risk of developing Alzheimer's disease.
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            Traumatic brain injury and risk of dementia in older veterans.

            Traumatic brain injury (TBI) is common in military personnel, and there is growing concern about the long-term effects of TBI on the brain; however, few studies have examined the association between TBI and risk of dementia in veterans.
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              Traumatic brain injury in later life increases risk for Parkinson disease.

              Traumatic brain injury (TBI) is thought to be a risk factor for Parkinson disease (PD), but results are conflicting. Many studies do not account for confounding or reverse causation. We sought to address these concerns by quantifying risk of PD after TBI compared to non-TBI trauma (NTT; defined as fractures).
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                Author and article information

                Contributors
                ed103520@edah.org.tw
                ed104283@edah.org.tw
                pipijer@gmail.com
                gordon168999@yahoo.com.tw
                ed107774@edah.org.tw
                ed106560@edah.org.tw
                wang1129073@hot.mail.com.tw
                y520729@gmail.com
                ytsun@mail.ncku.edu.tw
                866-975106080 , ed101393@gmail.com , ed101393@edah.org.tw
                Journal
                BMC Neurol
                BMC Neurol
                BMC Neurology
                BioMed Central (London )
                1471-2377
                5 November 2018
                5 November 2018
                2018
                : 18
                : 184
                Affiliations
                [1 ]Department of Family Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
                [2 ]ISNI 0000 0004 0637 1806, GRID grid.411447.3, School of Medicine for International Students, , I-Shou University, ; Kaohsiung, Taiwan
                [3 ]Department of Nephrology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
                [4 ]ISNI 0000 0004 0639 0054, GRID grid.412040.3, Neurosurgical Service, Department of Surgery, , National Cheng Kung University Hospital, ; Tainan, Taiwan
                [5 ]Department of Neurology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
                [6 ]Department of Neurosurgery, E-Da Hospital, I-Shou University, No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445 Taiwan
                [7 ]ISNI 0000 0004 0639 0054, GRID grid.412040.3, Department of Neurology, , National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, ; Tainan, Taiwan
                Author information
                http://orcid.org/0000-0002-1928-7502
                Article
                1187
                10.1186/s12883-018-1187-0
                6217762
                30396335
                0947b337-95ec-4d5f-972e-d7216dbb4bff
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 13 September 2017
                : 21 October 2018
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Neurology
                tbi,dementia,neurodegeneration,meta-analysis
                Neurology
                tbi, dementia, neurodegeneration, meta-analysis

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