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Article type: Systematic Review
Authors: Graham, Alicia | Livingston, Gill | Purnell, Lucy | Huntley, Jonathan; *
Affiliations: University College London, London, UK
Correspondence: [*] Correspondence to: Jonathan Huntley, University College London, Division of Psychiatry, 6th Floor, Maple House, 149 Tottenham Court Road, London W1T 7NF, UK. Tel.: +02076799294; E-mail: j.huntley@ucl.ac.uk.
Note: [] Prospero Registration Number CRD42020177723; (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CapRD42020177723).
Abstract: Background:Traumatic brain injury (TBI) increases the risk of future dementia and Alzheimer’s disease (AD). However, it is unclear whether this is true for mild TBI (mTBI). Objective:To explore the association between mTBI and subsequent risk of developing AD. Method:We systematically searched four electronic databases from January 1954 to April 2020. We included studies reporting primary data and where mTBI preceded AD by≥5 years. We meta-analyzed included studies for both high quality studies and studies with a follow up of > 10 years. Result:We included 5 of the 10,435 results found. Meta-analysis found a history of mTBI increased risk of AD (pooled relative risk = 1.18, 95% CI 1.11–1.25, N = 3,149,740). The sensitivity analysis including only studies in which mTBI preceded AD by > 10 years, excluded two very large studies and resulted in wider confidence intervals (RR = 2.02, 95% CI 0.66–6.21, N = 2307). Conclusion:There is an increased risk of AD following mTBI. Our findings of increased risk even with mTBI means it cannot be assumed that mild head injuries from sports are harmless. The sensitivity analysis suggests that we cannot exclude reverse causation, and longer follow up times are needed. Implementation of policy to reduce mTBIs, including in children and sportsmen, are urgently needed. Further research is needed on the effect of frequency and age at injury of mTBIs.
Keywords: Alzheimer’s disease, meta-analysis, risk factor, systematic review, traumatic brain injury
DOI: 10.3233/JAD-220069
Journal: Journal of Alzheimer's Disease, vol. 87, no. 3, pp. 969-979, 2022
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