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White Matter Hyperintensities Moderate the Association Between Diabetes and Non-AD Brain Atrophy
Jiangbo Cui, Zhaojun Liu, Wei Ying Tan, Joyce Ruifen Chong, Shin Hui On, Eddie Jun Yi Chong, Narayanaswamy Venketasubramanian, Mitchell K.P. Lai et al.. Diabetes Care, 2025-10-27
Topic: Brain proteins, microglia and lab models
Diabetes was not associated with brain atrophy cross-sectionally or longitudinally. Instead, an interactive effect between diabetes and WMHs on brain atrophy was observed. In Harmonization, this interaction was significant in cross-sectional analyses, affecting cortical gray matter and the frontal lobe. No interactive effect was found for AD-specific atrophy, and the observed interactive effect remained significant after adjusting for plasma pTau181. Cortical gray matter mediated the effect of diabetes on cognition at higher WMHs burden. These results were replicated in ADNI, where diabetes and WMHs interacted to accelerate brain atrophy over time. Our study demonstrated diabetes and WMHs synergistically contribute to brain atrophy independent of AD, suggesting diabetes-associated cognitive impairment is primarily driven by cerebrovascular disease rather than Alzheimer pathology.
Key findings
- Diabetes was not associated with brain atrophy cross-sectionally or longitudinally.
- Instead, an interactive effect between diabetes and WMHs on brain atrophy was observed.
- In Harmonization, this interaction was significant in cross-sectional analyses, affecting cortical gray matter and the frontal lobe.
- No interactive effect was found for AD-specific atrophy, and the observed interactive effect remained significant after adjusting for plasma pTau181.
- Cortical gray matter mediated the effect of diabetes on cognition at higher WMHs burden.
Why it matters
Diabetes alone was not linked to brain atrophy, but diabetes and white matter hyperintensities together were linked to more atrophy, independent of Alzheimer's pathology. This suggests that diabetes-related cognitive problems may be driven mainly by cerebrovascular disease, but the study does not test any treatment.
Study details
- Study designcross-sectional
- Participants112
- Evidence strengthModerate
How this study scored 52/100
Published in a leading specialty 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. We have no data on senior author's track record, so that was left out: it earned 50 of the 96 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Diabetes Care) |
| Journal's citation record | 4 / 4 | Diabetes Care: journal h-index 509 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 112 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 | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 1 / 3 | National University of Singapore: institution h-index 1,166 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41144252) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 50 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 50 of the 96 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.
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
Cui, J., Liu, Z., Tan, W. Y., Chong, J. R., On, S. H., Chong, E. J. Y., et al. (2025). White Matter Hyperintensities Moderate the Association Between Diabetes and Non-AD Brain Atrophy. Diabetes Care. https://doi.org/10.2337/dc25-1162
Vancouver
Cui J, Liu Z, Tan WY, Chong JR, On SH, Chong EJY, et al. White Matter Hyperintensities Moderate the Association Between Diabetes and Non-AD Brain Atrophy. Diabetes Care. 2025. doi:10.2337/dc25-1162. PMID: 41144252.
BibTeX
@article{cui2025-41144252,
author = {Cui, Jiangbo and Liu, Zhaojun and Tan, Wei Ying and Chong, Joyce Ruifen and On, Shin Hui and Chong, Eddie Jun Yi and Venketasubramanian, Narayanaswamy and Lai, Mitchell K.P. and others},
title = {{White Matter Hyperintensities Moderate the Association Between Diabetes and Non-AD Brain Atrophy}},
journal = {Diabetes Care},
year = {2025},
doi = {10.2337/dc25-1162},
pmid = {41144252},
url = {https://doi.org/10.2337/dc25-1162}
}
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