: Publication 17758

Publication 17758

Title:	COVID-19 related brain MRI changes and anticipated long-term dementia risk: A front-door-criterion-inspired approach
Journal:	Annals of Epidemiology
Published:	14 Feb 2026
Pubmed:	https://pubmed.ncbi.nlm.nih.gov/41698539/
DOI:	https://doi.org/10.1016/j.annepidem.2026.110054

Abstract

PURPOSE: Evaluating long-term effects of COVID-19 is challenging due to confounding and lack of comparable unexposed groups. The front-door criterion for causal inference identifies causal effects operating via specific pathways, even if unmeasured confounding occurs. We leverage the front-door criterion to estimate effects of COVID-19 on long-term dementia risk mediated by short-term brain magnetic resonance imaging (MRI) changes.</p>

METHODS: UK Biobank participants (n = 37,426) aged 55 + without prevalent dementia completed brain MRIs. Mediators were defined based on 31 MRI-derived variables previously shown to change due to COVID-19. We evaluated associations of these brain variables with incident all-cause dementia using confounder-adjusted Cox proportional-hazards models and combined results to infer effects of COVID-19 on dementia risk mediated via brain changes.</p>

RESULTS: Over 4.7 years (SD, 1.5) of follow-up, 112 incident dementia cases occurred. Of the 31 brain MRI-derived variables previously linked to COVID-19, 29 were associated with higher dementia incidence. Brain MRI changes of the magnitude induced on average by COVID-19 were associated with 9 % higher dementia hazard (HR: 1.09 [95 % CI, 1.06-1.12]).</p>

CONCLUSIONS: Front-door-criterion-inspired approaches can circumvent nearly intractable confounding and evaluate effects mediated by short-term physiologic changes. We find that MRI-based structural brain changes attributable to COVID-19 modestly increase dementia risk.</p>

Abstract

14 Keywords

11 Authors