Evidence map›Paper›PMID 41698539›Full record

ArticleAnnals of epidemiology2026

COVID-19 related brain MRI changes and anticipated long-term dementia risk: A front-door-criterion-inspired approach.

Jingxuan Wang, Erin L Ferguson, Ruijia Chen, Sarah F Ackley, Renaud La Joie, John Kornak, J Daniel Kelly, Hossein Estiri, John Hsu, Deborah Blacker and 1 more

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In one paragraph

Article in Annals of epidemiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Jingxuan WangDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, MA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA; Department of Epidemiology, Boston University, MA, USA.
Erin L FergusonDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
Ruijia ChenDepartment of Epidemiology, Boston University, MA, USA.
Sarah F AckleyDepartment of Epidemiology, Brown University, RI, USA.
Renaud La JoieMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences University of California, San Francisco, CA, USA.
John KornakDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
J Daniel KellyDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA; F.I. Proctor Foundation, University of California, San Francisco, CA, USA.
Hossein EstiriDepartment of Medicine, Massachusetts General Hospital, MA, USA; Department of Medicine, Harvard Medical School, MA, USA.
John HsuDepartment of Medicine, Harvard Medical School, MA, USA; Mongan Institute, Massachusetts General Hospital, MA, USA; Department of Health Care Policy, Harvard Medical School, MA, USA.
Deborah BlackerDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, MA, USA; Department of Psychiatry, Massachusetts General Hospital, MA, USA; Department of Psychiatry, Harvard Medical School, MA, USA.
M Maria GlymourDepartment of Epidemiology, Boston University, MA, USA. Electronic address: mglymour@bu.edu.

Funding

Mathematical Models of Tau-PET Measures and Cognitive Decline in Alzheimer's Disease Across the LifespanR00AG073454 · NIA · BROWN UNIVERSITY · PI Sarah Ackley · 2024 to 2026
$742k
Bridging Social Epidemiology and Policy for ADRD Prevention: Effects of Poverty Alleviation Policies on Alzheimer's Disease and Related Dementias Risk and DisparitiesK99AG088369 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Ruijia Chen · 2025 to 2026
$264k
The Impact of SARS-CoV-2 Infection and Vaccination on the Risk of Alzheimer’s Disease and Related DementiasK00AG083306 · NIA · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Jingxuan Wang · 2025 to 2026
$174k
The Impact of SARS-CoV-2 Infection and Vaccination on the Risk of Alzheimer’s Disease and Related DementiasF99AG083306 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WANG, JINGXUAN · 2023 to 2025
$72k
NIA NIH HHS F99 AG083306NIA NIH HHS K00 AG083306NIA NIH HHS K99 AG088369NIA NIH HHS R00 AG073454
6 · The paper itself

Abstract

purposeEvaluating 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.

methodsUK 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.

resultsOver 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]).

conclusionsFront-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.

Indexed as

BrainCOVID-19DementiaMagnetic Resonance ImagingAgedFemaleHumansMaleMiddle AgedPandemicsProportional Hazards ModelsRisk FactorsSARS-CoV-2UK BiobankUnited KingdomBrain magnetic resonance imagingCOVID-19DementiaFront-door criterion

Identifiers

PMID41698539
PMCPMC13142795

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.