Evidence map›Paper›PMID 42642661›Full record

ArticleNature medicine2026

Oligodendrocyte dysfunction in human age-related cognitive decline.

Georgina A Craig, Emeric Merour, Luise A Seeker, Annette J Haughian, Keon Arbabi, Jamie Rose, Alana Hoffmann, Jessica Thapar, Andrea Corsinotti, Stephen Mitchell and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

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

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

20 authors.

Georgina A CraigKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada. georgina.craig@unityhealth.to.ORCID http://orcid.org/0000-0003-3104-210X
Emeric MerourDepartment of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Luise A SeekerDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Annette J HaughianKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.
Keon ArbabiCentre for Addiction and Mental Health, Toronto, Ontario, Canada.
Jamie RoseUK Dementia Research Institute at The University of Edinburgh, Edinburgh, UK.
Alana HoffmannKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.
Jessica ThaparKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.
Andrea CorsinottiInstitute for Neuroscience and Cardiovascular Research, The University of Edinburgh, Edinburgh, UK.
Stephen MitchellWellcome Trust Centre for Cell Biology at King's Buildings, The University of Edinburgh, Edinburgh, UK.
Janie CorleyLothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-7551-1871
Susan D ShenkinLothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, UK.
Colin SmithInstitute for Neuroscience and Cardiovascular Research, The University of Edinburgh, Edinburgh, UK.
Tara L Spires-JonesUK Dementia Research Institute at The University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0003-2530-0598
Lu O SunDepartment of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Simon R CoxLothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0003-4036-3642
Anna WilliamsUK Dementia Research Institute at The University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-6329-382X
Shreejoy J TripathyCentre for Addiction and Mental Health, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-1007-9061
Brian PopkoDepartment of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-9948-2553
Véronique E MironKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada. veronique.miron@unityhealth.to.ORCID http://orcid.org/0000-0003-1738-0647

Funding

Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) 203844U.S. Department of Health & Human Services | National Institutes of Health (NIH) 4R01AG072080U.S. Department of Health & Human Services | National Institutes of Health (NIH) 5R35NS137478Wellcome Trust (Wellcome) 221890/Z/20/Z
6 · The paper itself

Abstract

Cognitive decline in aging impacts quality of life, for which therapeutic interventions are lacking. Why some individuals experience more severe cognitive decline with aging is unclear. Here we uncover a role for the brain's myelin-forming cells-oligodendrocytes-in explaining this variance. By investigating neuropathological and transcriptomic changes in human white matter associated with individual rates of cognitive decline in aging, we find that worse cognitive trajectories unexpectedly associate with smaller myelinated axon size, thicker myelin and more oligodendrocytes with downregulation of NRF2. Aged oligodendrocyte-specific NRF2-knockout mice showed attenuated cognitive improvement over time and mirrored the white matter pathology of human cognitive decline in aging. These findings place the oligodendrocyte as a contributor to cognitive decline and highlight the NRF2 pathway as a therapeutic target to preserve cognition in human aging.

Indexed as

AgingCognitive DysfunctionOligodendrogliaAgedAged, 80 and overAnimalsAxonsBrainFemaleHumansMaleMiceMice, KnockoutMyelin SheathNF-E2-Related Factor 2White MatterNFE2L2 protein, humanNF-E2-Related Factor 2

Identifiers

PMID42642661
PMCPMC13668666

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.