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White matter hyperintensity severity modifies gut metabolite association with cognitive outcomes
Naruchorn Kijpaisalratana, Chia‐Ling Phuah, Zsuzsanna Ament, Varun M. Bhave, Ana‐Lucia Garcia Guarniz, Jonathan A. Duskin, Catharine A. Couch, Marguerite R. Irvin et al.. The Journal of Prevention of Alzheimer s Disease, 2025-02-11
Topic: Brain proteins, microglia and lab models
Of 104 metabolites studied, glycodeoxycholic acid (GDCA) surpassed the false discovery rate and was associated the Alzheimer's Disease Assessment Scale-Cognitive Subscale version 13 (ADAS-Cog13) score (β = 0.12, 95 % CI = 0.05-0.20, p = 0.001) and cognitive impairment determined by mini-mental status exam (MMSE) (OR = 2.11, 95 % CI = 1.41-3.15, p < 0.001). GDCA was associated with higher ADAS-Cog13 in participants with low WMH burden (β = 0.21, 95% CI = 0.10-0.32, p < 0.001) but not in participants with high WMH burden (β = 0.04, 95 % CI = -0.07 to 0.14, p = 0.48; interaction p = 0.02). An elevated level of GDCA was associated with worse cognition. WMH severity modified the association between GDCA and cognitive outcomes.
Key findings
- Of 104 metabolites studied, glycodeoxycholic acid (GDCA) surpassed the false discovery rate and was associated the Alzheimer's Disease Assessment Scale-Cognitive Subscale version 13 (ADAS-Cog13) score (β = 0.12, 95 % CI = 0.05-0.20, p = 0.001) and cognitive impairment determined by mini-mental status exam (MMSE) (OR = 2.11, 95 % CI = 1.41-3.15, p < 0.001).
- GDCA was associated with higher ADAS-Cog13 in participants with low WMH burden (β = 0.21, 95% CI = 0.10-0.32, p < 0.001) but not in participants with high WMH burden (β = 0.04, 95 % CI = -0.07 to 0.14, p = 0.48; interaction p = 0.02).
- An elevated level of GDCA was associated with worse cognition.
- WMH severity modified the association between GDCA and cognitive outcomes.
Why it matters
Higher levels of a gut metabolite called glycodeoxycholic acid were linked to worse cognition, but only in people with low white matter hyperintensity burden, not in those with high burden. This is a cross-sectional finding and does not show that changing this metabolite would affect memory or dementia.
Study details
- Study designcross-sectional
- Participants578
- Effect sizeOR = 2.11
- Evidence strengthModerate
How this study scored 55/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of Prevention of Alzheimer s Disease) |
| Journal's citation record | 0 / 4 | The Journal of Prevention of Alzheimer s Disease: journal h-index 63 (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 | 578 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 1 / 5 | 2.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.4× 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 William Taylor Kimberly: h-index 59 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39939193) |
| Free to read | 2 / 2 | Free to read |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.tjpad.2025.100086
- PubMed: 39939193
- Original source →
- Free full text: The Journal of Prevention of Alzheimer s Disease →
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
Kijpaisalratana, N., Phuah, C., Ament, Z., Bhave, V. M., Guarniz, A. G., Duskin, J. A., et al. (2025). White matter hyperintensity severity modifies gut metabolite association with cognitive outcomes. The Journal of Prevention of Alzheimer s Disease. https://doi.org/10.1016/j.tjpad.2025.100086
Vancouver
Kijpaisalratana N, Phuah C, Ament Z, Bhave VM, Guarniz AG, Duskin JA, et al. White matter hyperintensity severity modifies gut metabolite association with cognitive outcomes. The Journal of Prevention of Alzheimer s Disease. 2025. doi:10.1016/j.tjpad.2025.100086. PMID: 39939193.
BibTeX
@article{kijpaisalratana2025-39939193,
author = {Kijpaisalratana, Naruchorn and Phuah, Chia‐Ling and Ament, Zsuzsanna and Bhave, Varun M. and Guarniz, Ana‐Lucia Garcia and Duskin, Jonathan A. and Couch, Catharine A. and Irvin, Marguerite R. and others},
title = {{White matter hyperintensity severity modifies gut metabolite association with cognitive outcomes}},
journal = {The Journal of Prevention of Alzheimer s Disease},
year = {2025},
doi = {10.1016/j.tjpad.2025.100086},
pmid = {39939193},
url = {https://doi.org/10.1016/j.tjpad.2025.100086}
}
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