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Characterizing spatiotemporal white matter hyperintensity pathophysiology in vivo to disentangle vascular and neurodegenerative contributions
Olivier Parent, Zaki Alasmar, Sophia Osborne, Aurélie Bussy, Manuela Costantino, Jérémie P. Fouquet, Daniela Quesada, Adeline Bernier et al.. Nature Communications, 2026-03-31
Topic: Brain proteins, microglia and lab models
White matter hyperintensities (WMHs) are neuroimaging markers widely interpreted as caused by cerebral small vessel disease, yet emerging evidence suggests that a subset may have a neurodegenerative etiology. Current imaging methods have lacked the specificity to disentangle biological processes underlying WMHs in vivo. Here, we used voxel-level normative modeling and seven microstructural MRI markers with complementary biophysical sensitivities to generate single-subject high-resolution WMH pathophysiology maps in a large cohort (n = 32,526). We calculated data-driven spatial patterns of similar WMHs, revealing distinct periventricular, posterior, and anterior clusters. We identified a reproducible WMH signature linked to dementia and Alzheimer's disease, characterized by a posterior predominance and a pathophysiological pattern indicative of selective fiber degeneration. Posterior WMHs connected cortical regions vulnerable to tau pathology. Our framework helps parsing vascular and neurodegenerative contributions of WMHs in vivo, which could alter the course of treatment strategies and provide nuanced interpretations of research findings.
Key findings
- White matter hyperintensities (WMHs) are neuroimaging markers widely interpreted as caused by cerebral small vessel disease, yet emerging evidence suggests that a subset may have a neurodegenerative etiology.
Why it matters
Using MRI in a large cohort, the researchers identified a pattern of white matter hyperintensities with a posterior predominance that was linked to dementia and Alzheimer's disease and appeared to reflect fibre degeneration rather than only vessel disease. This may help separate vascular from neurodegenerative causes of these lesions, but it does not test any treatment.
Study details
- Participants32,526
- Evidence strengthModerate
How this study scored 58/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature Communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 4 / 4 | 32,526 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 5 / 6 | Cited 30.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author M. Mallar Chakravarty: h-index 84 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | McGill University: institution h-index 1,373 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41916976) |
| Free to read | 2 / 2 | Free to read |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41467-026-70832-2
- PubMed: 41916976
- Original source →
- Free full text: Nature Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Parent, O., Alasmar, Z., Osborne, S., Bussy, A., Costantino, M., Fouquet, J. P., et al. (2026). Characterizing spatiotemporal white matter hyperintensity pathophysiology in vivo to disentangle vascular and neurodegenerative contributions. Nature Communications. https://doi.org/10.1038/s41467-026-70832-2
Vancouver
Parent O, Alasmar Z, Osborne S, Bussy A, Costantino M, Fouquet JP, et al. Characterizing spatiotemporal white matter hyperintensity pathophysiology in vivo to disentangle vascular and neurodegenerative contributions. Nature Communications. 2026. doi:10.1038/s41467-026-70832-2. PMID: 41916976.
BibTeX
@article{parent2026-41916976,
author = {Parent, Olivier and Alasmar, Zaki and Osborne, Sophia and Bussy, Aurélie and Costantino, Manuela and Fouquet, Jérémie P. and Quesada, Daniela and Bernier, Adeline and others},
title = {{Characterizing spatiotemporal white matter hyperintensity pathophysiology in vivo to disentangle vascular and neurodegenerative contributions}},
journal = {Nature Communications},
year = {2026},
doi = {10.1038/s41467-026-70832-2},
pmid = {41916976},
url = {https://doi.org/10.1038/s41467-026-70832-2}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.