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Polygenic risk for white matter hyperintensities is associated with early cerebrovascular events partly through hemodynamic measures in cognitively unimpaired middle-aged and older adults with low cardiovascular risk
Patricia Genius, Blanca Rodríguez‐Fernández, Carolina Minguillón, Brugulat-Serrat Anna, Jordi Huguet, Manel Esteller, Carole H. Sudre, Marta Cortés‐Canteli et al.. Frontiers in Neurology, 2026-01-05
Topic: Brain proteins, microglia and lab models
They are often found in middle-aged individuals and are associated with a greater risk of stroke and vascular dementia. Results Genetic predisposition to WMH was associated with larger global and regional WMHV after adjusting for age and sex, specifically in frontal areas. In this group, larger WMHV were associated with poorer executive function. Group-stratified analyses showed significant correlations particularly among older participants, those with hypercholesterolemia and those with lower educational attainment. Interpretation These findings support a polygenic contribution to cerebrovascular burden and nominate cardiac function as a biological link along the heart-brain axis. While the PRS WMH is not yet clinically actionable, our results propose and prioritize hemodynamic monitoring as an early, testable intervention in genetically susceptible individuals, to help prevent cerebrovascular damage and downstream cognitive impairment in healthy participants with low cardiovascular risk profile.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Genius, P., Rodríguez‐Fernández, B., Minguillón, C., Anna, B.-S., Huguet, J., Esteller, M., et al. (2026). Polygenic risk for white matter hyperintensities is associated with early cerebrovascular events partly through hemodynamic measures in cognitively unimpaired middle-aged and older adults with low cardiovascular risk. Frontiers in Neurology. https://doi.org/10.3389/fneur.2025.1667424
Vancouver
Genius P, Rodríguez‐Fernández B, Minguillón C, Anna B.-S, Huguet J, Esteller M, et al. Polygenic risk for white matter hyperintensities is associated with early cerebrovascular events partly through hemodynamic measures in cognitively unimpaired middle-aged and older adults with low cardiovascular risk. Frontiers in Neurology. 2026. doi:10.3389/fneur.2025.1667424. PMID: 41561329.
BibTeX
@article{genius2026-41561329,
author = {Genius, Patricia and Rodríguez‐Fernández, Blanca and Minguillón, Carolina and Anna, Brugulat-Serrat and Huguet, Jordi and Esteller, Manel and Sudre, Carole H. and Cortés‐Canteli, Marta and others},
title = {{Polygenic risk for white matter hyperintensities is associated with early cerebrovascular events partly through hemodynamic measures in cognitively unimpaired middle-aged and older adults with low cardiovascular risk}},
journal = {Frontiers in Neurology},
year = {2026},
doi = {10.3389/fneur.2025.1667424},
pmid = {41561329},
url = {https://doi.org/10.3389/fneur.2025.1667424}
}
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.
Key findings
- They are often found in middle-aged individuals and are associated with a greater risk of stroke and vascular dementia.
- Results Genetic predisposition to WMH was associated with larger global and regional WMHV after adjusting for age and sex, specifically in frontal areas.
- In this group, larger WMHV were associated with poorer executive function.
- Group-stratified analyses showed significant correlations particularly among older participants, those with hypercholesterolemia and those with lower educational attainment.
- Interpretation These findings support a polygenic contribution to cerebrovascular burden and nominate cardiac function as a biological link along the heart-brain axis.
Why it matters
This study found that genetic predisposition to white matter hyperintensities was linked to larger volumes of them and to poorer executive function, with cardiac function proposed as a biological link. The authors note the polygenic risk score is not yet clinically actionable but suggest hemodynamic monitoring as an early, testable intervention in genetically susceptible people.
Study details
- Participants1,072
- Evidence strengthLow
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in Neurology) |
| Journal's citation record | 2 / 4 | Frontiers in Neurology: journal h-index 162 (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 | 1 / 5 | Rated “low” 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 | 3 / 4 | 1,072 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 | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.3× 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 | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Natàlia Vilor‐Tejedor: h-index 31 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 32 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41561329) |
| Free to read | 2 / 2 | Free to read |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fneur.2025.1667424
- PubMed: 41561329
- Original source →
- Free full text: Frontiers in Neurology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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