Dementia risk due to traumatic brain injury in subtypes of dementia in the Welsh population

Simmonds, Emily, Han, Jun, Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950, Sharp, David J., Massey, Thomas H. ORCID: https://orcid.org/0000-0002-9804-2131 and Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483 2025. Dementia risk due to traumatic brain injury in subtypes of dementia in the Welsh population. Neurology 105 (3) , e213866. 10.1212/wnl.0000000000213866

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Abstract

Background and Objectives Traumatic brain injury (TBI) can increase vulnerability to neurodegenerative disorders. The association between TBI and dementia has been previously reported, but studies have relied on self-reporting of TBI and often do not appropriately adjust for relevant risk factors or cover enough time to include both individuals at age of highest TBI risk and age of dementia onset. This study uses electronic health records, which include over 20 years of data and 1.7 million individuals with hospital or general practitioner diagnoses of dementia and TBI. Therefore, the aim of this study was to assess the association between TBI and dementia and between TBI and dementia subtypes (Alzheimer disease [AD], vascular dementia [VaD], and unspecified dementia). Methods We performed a population-based study using Welsh (UK) electronic health records to estimate effect of TBI on the risk of dementia for individuals aged between 30 and 65 years in 1999 without a previous dementia diagnosis. The long-term risk of dementia after TBI was established using Cox proportional hazard models adjusting for sex, social deprivation, and other comorbidities. The effect of the time between TBI and dementia was investigated with time-stratified analyses. We assessed separately the risks of AD, VaD, and unspecified dementia related to TBI. Results Our study investigated 42,974 individuals with dementia (mean diagnosis age of 70 [SD = 10.5]), 10,164 individuals with a history of TBI, and 1,737,480 controls (mean age of 62 [SD = 11.9]). 49% of all individuals were female. TBI was associated with increased risk of dementia (hazard ratio [HR] = 2.32, 95% CI [1.88–2.85], p = 3.8 × 10−15), with the risk increasing for multiple TBIs (HR = 1.22, 95% CI [1.08–1.38], p = 1.8 × 10−03). The effect size of association between TBI and dementia was higher in people diagnosed with VaD (HR = 1.71, 95% CI [1.06–2.75], p = 0.027) and unspecified dementia (HR = 1.90, 95% CI [1.29–2.80], p = 0.0011) compared with the AD group (HR = 1.44, 95% CI [0.84–2.48], p = 0.189). Discussion Our study confirms that TBI increases dementia risk. We have shown a higher risk of VaD and unspecified dementia in those with a TBI, compared with AD. This study will direct future research into which biological mechanisms drive the association between TBI and dementia.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Lippincott, Williams & Wilkins
ISSN:	0028-3878
Date of First Compliant Deposit:	15 July 2025
Date of Acceptance:	9 May 2025
Last Modified:	15 Jul 2025 14:15
URI:	https://orca.cardiff.ac.uk/id/eprint/179850

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