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White matter hyperintensity burden predicts domain-specific cognitive decline across the Alzheimer’s disease continuum
Hamide Nasiri, Fatemeh Khosravi, Parsa Saberian, Melika Kavian, Mehrdad Mozafar, Paria Torabi, Tannaz Malekzadeh, Seyed Morteza Hadavi et al.. Scientific Reports, 2025-11-25
Topic: Amyloid, tau and blood-test diagnosis
White matter hyperintensity (WMH), indicative of cerebral small vessel disease, has emerged as a potential biomarker for cognitive decline in Alzheimer's disease (AD). However, their predictive role across specific cognitive domains within the AD spectrum remains unclear. This study investigates the relationship between WMH volume and cognitive performance in memory, executive function, and language across the AD continuum. A cross-sectional analysis was conducted using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), comprising 557 participants categorized into cognitively normal (CN; n = 158), mild cognitive impairment (MCI; n = 334), and Alzheimer's dementia (AD; n = 65) groups. Cognitive function was assessed using composite scores for memory (ADNI-MEM), executive function (ADNI-EF), and language (ADNI-LAN). WMH volume was quantified through validated Bayesian segmentation of MRI data. Associations between cognitive scores and WMH volume, adjusted for age, gender, APOE ε4 status, and vascular risk factors, were evaluated via multiple linear regression analyses. WMH volume showed numerically progressive increases from CN to MCI and AD groups; however, between-group differences did not reach statistical significance. Within the MCI group, significant negative associations emerged between WMH volume and memory (β=-0.13, adjusted p = 0.045) and language scores (β=-0.12, adjusted p = 0.045). Conversely, these relationships were absent in both the CN and AD groups. WMH volume relates specifically to declines in memory and language abilities, particularly in individuals with MCI. These results support using WMH measurements as early markers to identify cognitive decline in AD, potentially helping to guide earlier diagnosis and treatment decisions.
Key findings
- Within the MCI group, significant negative associations emerged between WMH volume and memory (β=-0.13, adjusted p = 0.045) and language scores (β=-0.12, adjusted p = 0.045).
- These results support using WMH measurements as early markers to identify cognitive decline in AD, potentially helping to guide earlier diagnosis and treatment decisions.
Why it matters
In people with mild cognitive impairment, higher white matter hyperintensity volume was linked to worse memory and language scores, though differences between cognitive groups were not statistically significant. The authors suggest white matter hyperintensity measurement may help identify early cognitive decline, but this is a cross-sectional study and does not test treatment.
Study details
- Study designcross-sectional
- Participants158
- Evidence strengthLow
How this study scored 51/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Scientific Reports) |
| Journal's citation record | 3 / 4 | Scientific Reports: journal h-index 463 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 158 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 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 3.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Maryam Bemanalizadeh: h-index 15 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Tehran University of Medical Sciences: institution h-index 810 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 16 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41290806) |
| Free to read | 2 / 2 | Free to read |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41598-025-25694-x
- PubMed: 41290806
- Original source →
- Free full text: Scientific Reports →
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
Nasiri, H., Khosravi, F., Saberian, P., Kavian, M., Mozafar, M., Torabi, P., et al. (2025). White matter hyperintensity burden predicts domain-specific cognitive decline across the Alzheimer’s disease continuum. Scientific Reports. https://doi.org/10.1038/s41598-025-25694-x
Vancouver
Nasiri H, Khosravi F, Saberian P, Kavian M, Mozafar M, Torabi P, et al. White matter hyperintensity burden predicts domain-specific cognitive decline across the Alzheimer’s disease continuum. Scientific Reports. 2025. doi:10.1038/s41598-025-25694-x. PMID: 41290806.
BibTeX
@article{nasiri2025-41290806,
author = {Nasiri, Hamide and Khosravi, Fatemeh and Saberian, Parsa and Kavian, Melika and Mozafar, Mehrdad and Torabi, Paria and Malekzadeh, Tannaz and Hadavi, Seyed Morteza and others},
title = {{White matter hyperintensity burden predicts domain-specific cognitive decline across the Alzheimer’s disease continuum}},
journal = {Scientific Reports},
year = {2025},
doi = {10.1038/s41598-025-25694-x},
pmid = {41290806},
url = {https://doi.org/10.1038/s41598-025-25694-x}
}
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