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Metabolic and vascular contributions to dementia: Soluble epoxide hydrolase‐derived linoleic acid oxylipins and glycemic status are related to cerebral small vessel disease markers, atrophy, and cognitive performance
Si Won Ryoo, William Z. Lin, Alexandra Magliocco, Myuri T. Ruthirakuhan, Yuen Yan Wong, Sofia E. Perfetto, Celine Huang, Natasha Z. Anita et al.. Alzheimer s & Dementia, 2025-10-01
Topic: Brain proteins, microglia and lab models
With elevated HbA1c, greater LA-derived diol/epoxide ratios were associated with greater WMH volume (β [95% CI] = 0.565 [0.100, 1.030], p = 0.017), lower global BPF (β [95% CI] = -0.476 [-0.903, -0.048], p = 0.029), and poorer memory performance (β [95% CI] = -0.603 [-1.070, -0.136], p = 0.012), such that detrimental associations were observed only in T2DM. Cytochrome P450-sEH metabolites may indicate a novel metabolic-vascular contribution to dementia in individuals with T2DM. CLINICAL TRIALS REGISTRATION INFORMATION: ClinicalTrials.gov Identifier NCT04104373. HIGHLIGHTS: LA-derived sEH metabolite (diol) to substrate (epoxide) ratio was lower in individuals with diabetes. The diol/epoxide ratio with high HbA1c contributed to SVD and brain atrophy. The CYP450-sEH pathway may link metabolic and vascular contributions to dementia. sEH may be a potential therapeutic target in individuals with diabetes.
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APA 7th
Ryoo, S. W., Lin, W. Z., Magliocco, A., Ruthirakuhan, M. T., Wong, Y. Y., Perfetto, S. E., et al. (2025). Metabolic and vascular contributions to dementia: Soluble epoxide hydrolase‐derived linoleic acid oxylipins and glycemic status are related to cerebral small vessel disease markers, atrophy, and cognitive performance. Alzheimer s & Dementia. https://doi.org/10.1002/alz.70718
Vancouver
Ryoo SW, Lin WZ, Magliocco A, Ruthirakuhan MT, Wong YY, Perfetto SE, et al. Metabolic and vascular contributions to dementia: Soluble epoxide hydrolase‐derived linoleic acid oxylipins and glycemic status are related to cerebral small vessel disease markers, atrophy, and cognitive performance. Alzheimer s & Dementia. 2025. doi:10.1002/alz.70718. PMID: 41059602.
BibTeX
@article{ryoo2025-41059602,
author = {Ryoo, Si Won and Lin, William Z. and Magliocco, Alexandra and Ruthirakuhan, Myuri T. and Wong, Yuen Yan and Perfetto, Sofia E. and Huang, Celine and Anita, Natasha Z. and others},
title = {{Metabolic and vascular contributions to dementia: Soluble epoxide hydrolase‐derived linoleic acid oxylipins and glycemic status are related to cerebral small vessel disease markers, atrophy, and cognitive performance}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz.70718},
pmid = {41059602},
url = {https://doi.org/10.1002/alz.70718}
}
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
- With elevated HbA1c, greater LA-derived diol/epoxide ratios were associated with greater WMH volume (β [95% CI] = 0.565 [0.100, 1.030], p = 0.017), lower global BPF (β [95% CI] = -0.476 [-0.903, -0.048], p = 0.029), and poorer memory performance (β [95% CI] = -0.603 [-1.070, -0.136], p = 0.012), such that detrimental associations were observed only in T2DM.
- Cytochrome P450-sEH metabolites may indicate a novel metabolic-vascular contribution to dementia in individuals with T2DM.
- CLINICAL TRIALS REGISTRATION INFORMATION: ClinicalTrials.gov Identifier NCT04104373.
- HIGHLIGHTS: LA-derived sEH metabolite (diol) to substrate (epoxide) ratio was lower in individuals with diabetes.
- The diol/epoxide ratio with high HbA1c contributed to SVD and brain atrophy.
Why it matters
In people with type 2 diabetes, higher HbA1c combined with greater linoleic acid-derived diol/epoxide ratios was associated with greater white matter hyperintensity volume, lower brain parenchymal fraction, and poorer memory. The authors suggest soluble epoxide hydrolase may be a potential therapeutic target in diabetes, but this is an association study and not a treatment trial.
Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / 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 35 of the 96 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization 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 | 0.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 1 / 6 | Cited 0.6× 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 | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | University of Toronto: institution h-index 1,923 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 16 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41059602) |
| Free to read | 2 / 2 | Free to read |
| Points | 35 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 35 of the 96 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
What each of these 20 components measures, and what this score is not →
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