Traumatic brain injury is recognised as a major risk factor for dementia, with around 3-15% of cases in the community a result of previous brain injury. In line with this, former contact sports athletes exposed to high levels of head impacts and brain injuries have higher risk of neurodegenerative brain diseases like Alzheimer, Parkinson or motor neuron disease. Reasons for this association are not clear. Research looking at health outcomes following brain injury suggest that wider general health is also affected: for example, rates of heart disease and mental health disorders are higher in brain injury survivors (vs. people without such injury). These conditions, in themselves and independent of brain injury, are also risk factors for dementia and related conditions, which might be one reason for higher dementia in these patients. Against this, however, former athlete studies show wider lifelong health is better. In other words, the relationship between brain injury and dementia risk is complex and remains poorly understood but might be influenced by wider health outcomes after brain injury, not just the damage to the brain itself.
There is, therefore, a need to better understand the link between traumatic brain injury and neurodegenerative brain diseases, and the role of wider health outcomes in ‘at risk’ populations in contributing to this. This will then allow us to explore interventions to reduce dementia risk after injury. Our proposal, LATE-TBI, seeks to access population level data to investigate the complex relationship between traumatic brain injury and lifelong health, in particular dementia.
A history of traumatic brain injury (TBI) is recognised as a major risk factor for neurodegenerative disease (NDD), with around 3-15% of dementia in the community thought to be a consequence of prior TBI exposure. In line with this, former contact sports with histories of exposure to repetitive TBI and head impacts have high risk of neurodegenerative disease when compared to general population datasets. However, reasons why TBI might increase risk of NDD remain uncertain. Studies of TBI outcomes in the general population report that wider general health is also impacted, including higher rates of cardiovascular disease and mental health disorder in TBI survivors, which are, in themselves, recognised risk factors for NDD. However, in contrast to these general population data, observations in former athletes report better wider health, including lower cardiovascular disease and mental health disorder.
The relationship between TBI and risk of NDD is complex and likely to reflect an interaction between the direct consequences of the injury to the brain and the influence of TBI on wider systemic health, in turn, indirectly impacting on brain health. To better understand the relationship between TBI and late NDD risk there is a need to gain a more holistic insight into lifelong health outcomes following TBI exposure and their potential interactions in modifying risk.
We will contrast baseline TBI vs. n=3 controls matched for age, sex, deprivation and years of up-to-standard (UTS) data, in terms of subsequent mortality and mental health outcomes. Participants will require at least 7 years up to UTS: one for exposure, one for covariate ascertainment, and five years for condition incidence (where a GOLD UTS date is assigned to a CPRD practice and the data recorded by the practice are of an acceptable research standard). Conditions will be based on a priori Read/SNOMED code lists.
• History of traumatic brain injury
• Primary and secondary causes of death, specifically deaths from the most common causes in the community (diseases of the circulatory system; diseases of the respiratory system; cancer; neurodegenerative disease) or where cause of death is recorded as suicide.
• Diagnosis of mental health disorder, specifically diagnosis of the most common mental health disorders in the community (anxiety and stress disorder; depression; alcohol use disorder; drug use disorder; bipolar and affective mood disorder).
• Diagnosis of neurodegenerative disease, specifically diagnoses of common dementias and neurodegenerative diseases (all neurodegenerative diseases; dementia not otherwise specified; Alzheimer’s disease; non-Alzheimer’s dementias; motor neuron disease; and Parkinson’s disease)
• Prescribing of medications for dementia, specifically prescribing of drugs listed under Section 4.11 of the British National Formulary.
William Stewart - Chief Investigator - University of Glasgow
Donald Lyall - Corresponding Applicant - University of Glasgow
Bhautesh Jani - Collaborator - University of Glasgow
Claire Hastie - Collaborator - University of Glasgow
Daniel Mackay - Collaborator - University of Glasgow
Emma Russell - Collaborator - University of Glasgow
Frederick Ho - Collaborator - University of Glasgow
Jill Pell - Collaborator - University of Glasgow
Jim Lewsey - Collaborator - University of Glasgow
Jordan Canning - Collaborator - University of Glasgow
Michael Fleming - Collaborator - University of Glasgow
Robert Pearsall - Collaborator - LANARKSHIRE
Xingxing Zhu - Collaborator - University of Glasgow
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation