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Is dementia more likely following traumatic brain injury? A systematic review

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Abstract

Background

The association between traumatic brain injury (TBI) and dementia is controversial, and of growing importance considering the ageing demography of TBI.

Objective

To review the scope and quality of the existing literature investigating the relationship between TBI and dementia.

Methods

We conducted a systematic review following PRISMA guidelines. Studies that compared TBI exposure and dementia risk were included. Studies were formally assessed for quality with a validated quality-assessment tool.

Results

44 studies were included in the final analysis. 75% (n = 33) were cohort studies and data collection was predominantly retrospective (n = 30, 66.7%). 25 studies (56.8%) found a positive relationship between TBI and dementia. Clearly defined and valid measures of assessing TBI history were lacking (case–control studies—88.9%, cohort studies—52.9%). Most studies failed to justify a sample size (case–control studies—77.8%, cohort studies—91.2%), blind assessors to exposure (case–control—66.7%) or blind assessors to exposure status (cohort—3.00%). Studies that identified a relationship between TBI and dementia had a longer median follow-up time (120 months vs 48 months, p = 0.022) and were more likely to use validated TBI definitions (p = 0.01). Studies which clearly defined TBI exposure (p = 0.013) and accounted for TBI severity (p = 0.036) were also more likely to identify an association between TBI and dementia. There was no consensus method by which studies diagnosed dementia and neuropathological confirmation was only available in 15.5% of studies.

Conclusions

Our review suggests a relationship between TBI and dementia, but we are unable to predict the risk of dementia for an individual following TBI. Our conclusions are limited by heterogeneity in both exposure and outcome reporting and by poor study quality. Future studies should; (a) use validated methods to define TBI, accounting for TBI severity; (b) follow consensus agreement on criteria for dementia diagnosis; and (c) undertake follow-up that is both longitudinal, to determine if there is a progressive neurodegenerative change or static post-traumatic deficit, and of sufficient duration.

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Fig. 1

From: Moher et al. [16]

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Data Availability

The data used to support the findings of this study are included in the article.

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Acknowledgements

PJH is supported by the NIHR (Senior Investigator Award, Global Health Research Group on Acquired Brain and Spine Injury, Medtech Co-operative for Acute Brain Injury and Cambridge BRC) and the Royal College of Surgeons of England.

Author information

Author notes

  1. John Gerrard Hanrahan and Charlotte Burford joint first authorship with equal contributorship.

Authors and Affiliations

  1. Department of Clinical Neurosciences, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK

    John Gerrard Hanrahan, Palani Nagappan, Shivani Rajkumar, Angelos Kolias, Adel Helmy & Peter John Hutchinson

  2. Department of General Surgery, East Kent University Hospitals NHS Foundation Trust, Ashford, UK

    Charlotte Burford

  3. Bart’s and the London Medical School, Queen Mary University of London, London, UK

    Gideon Adegboyega

Authors
  1. John Gerrard Hanrahan
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  2. Charlotte Burford
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  3. Palani Nagappan
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  4. Gideon Adegboyega
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  5. Shivani Rajkumar
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Corresponding author

Correspondence to Charlotte Burford.

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Conflicts of interest

No conflict of interests is reported from the authorship.

Ethical standard statement

Ethical approval was not required because this study retrieved and synthesised data from already published studies.

Appendices

Appendix 1: Search strategy

(Craniocerebral Trauma or Brain injuries, Traumatic or head trauma.mp. or traumatic brain injury.mp. or TBI.mp. or brain injuries or brain injury.mpm. or head injury.mp.) and (dementia.mp or dementia/ or dementia, muilti-infarct/ or frontotemporal dementia/ or dementia, Vascular/ or Alzheimer disease or Chronic Traumatic encephalopathy).

Appendix 2: Eligibility criteria

We included any study that investigated the relationship between dementia and TBI. The population of interest was individuals with a past medical history of TBI. All comparisons were included to capture the scope and quality of the literature and facilitate statistical comparison where possible. Outcomes pertaining to the development of dementia were included.

We excluded non-clinical studies, case-reports and non-peer reviewed articles. We also excluded systematic reviews, literature reviews and meta-analyses but examined their reference lists. If a study included dementia but had other diagnoses which could not be individually extracted, it was excluded.

Appendix 3: Quality assessment methodology

Participants were deemed to have been recruited from the same period if they were recruited within a window of 10-years. Determination as to whether the timeframe was sufficient to observe an association between the exposure (TBI) and outcome (dementia) was taken within the context of the participants age at the time of study and follow-up window of the study. For example, a follow-up time of 5 years for a cohort with an average age of 70 would be deemed sufficient to observe an association (assuming an average age of onset of dementia between 60 and 70 years) but a follow-up of 5 years in a cohort with an average age of 45, whose exposure was given as any time > 1 year prior to the study, would not be deemed sufficient. Studies were deemed to have considered levels of exposure if they attempted to interrogate an association between the severity of TBI and dementia. Studies that specified if participants had experienced single or multiple episodes of TBI or attempted to compare those with single episodes to those with multiple episodes were considered to have assessed the exposure repeatedly over time. Finally, studies were scored as having controlled for confounding variables if any attempt at multivariate analysis was made for variables more than age and gender.

Total scores were calculated for each study with case–control studies scoring a maximum of 14 and cohort studies scoring a maximum of 12. These scores were used to generate an overall qualitative rating of either 'Poor', 'Fair' or 'Good'.

Appendix 4: Data collection

Study characteristics

Study designs were categorised according to the hierarchy of evidence, noting recruitment of individuals, study aims, inclusion criteria, exclusion criteria and comparisons made.

Population characteristics

Sample sizes of populations and comparisons were noted, alongside distributions of genders. We also examined age determined by each study, age at injury and age of dementia onset. These factors are important in examining the temporality between the initial injury and studied outcome (dementia) or documentation of time from injury to dementia diagnosis. We also noted specific populations studied.

TBI characteristics

We examined whether individuals sustained single or multiple injuries and documented loss of consciousness. Diagnostic criteria for TBI were noted, alongside grading of severity, TBI diagnoses, mechanisms of injury and imaging findings at the injury.

Dementia characteristics

Dementia definition or subtypes studied were extracted. We also noted the diagnostic criteria, ascertainment of dementia diagnosis and severity.

Outcomes

We noted whether studies reported positive or negative findings and extracted statistics reporting associations between TBI and dementia. A relationship was defined as a statistically significant finding of either increased incidence of dementia in patients with a history of head injury or earlier age of onset of dementia in patients with a history of head injury. We also noted multivariate analyses and confounding factors adjusted for.

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Hanrahan, J.G., Burford, C., Nagappan, P. et al. Is dementia more likely following traumatic brain injury? A systematic review. J Neurol 270, 3022–3051 (2023). https://doi.org/10.1007/s00415-023-11614-4

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