Head injury/traumatic brain injury and the risk of dementia: An observational and Mendelian randomization study - 09/01/26

Doi : 10.1016/j.tjpad.2025.100468

Ziyu Ouyang ^a, Bin Jiao ^a,^b,^c,^d,^e, Xuewen Xiao ^a,^b,^c,^d,^e, Qijie Yang ^a, Yuan Zhu ^a, Lu Shen ^a,^b,^c,^d,^e,^f, Nan Li ^a,^b,^d,^e,^⁎
^a Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
^b Bioinformatics Center & National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, China
^c Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China
^d Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China
^e Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China
^f Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan, China

^⁎Corresponding author at: Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, Hunan, China.Xiangya HospitalCentral South University87 Xiangya RdChangshaHunanChina

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Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Friday 09 January 2026

Abstract

Background

This study aimed to investigate the link between head injury (HI)/traumatic brain injury (TBI) and dementia risk, as it remains unclear.

Methods

We examined the associations between HI/TBI-related factors, including the frequency of HIs and the severity of TBI, and the risk of dementia ( n = 397,581), as well as neuroimaging outcomes ( n = 42,380) using prospective data (50 years at baseline) from the UK Biobank. In the observational analyses, Cox proportional-hazards modeling and logistic regression were used to estimate the associations between factors. Mendelian randomization (MR) was conducted to investigate the underlying causality between TBI ( n = 392,423, n _cases =19,842) and Alzheimer's disease (AD) ( n = 41,944, n _cases =21,982).

Results

During the 12.5-year follow-up period, 7524 participants developed dementia. HI and TBI conferred an increased dementia risk (hazard ratio (HR)=1.72, 95 % confidence interval (CI): 1.50–1.97; HR=1.86, 95 % CI: 1.46–2.38, respectively). The risk increased in relation to recurrent HIs (HR=4.05, 95 % CI: 2.24–7.32) or severe TBI (HR=4.50, 95 % CI: 3.18–6.37). Dementia risk was highest during the first 30 months following HI occurrence (HR=2.20, 95 % CI: 1.66–2.92), whereas there was no association after 40 years post-HI. Patients with recurrent HIs also exhibited reduced hippocampal volumes and increased white matter hyperintensity. HI was additionally associated with poorer reasoning ability and longer reaction time. Besides, the MR analysis supported a causal association between TBI and AD (odds ratio (OR)=1.17, 95 % CI: 1.01–1.37).