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Liver–metabolic stress, apolipoprotein E ε4, and cognition and amyloid burden: findings from the dementia platform Korea trial-ready registry
Young Hyeon Ahn, Jin Gu Kang, DaHyeon Choi, 김대진, Chan-Mo Yang, S. H. Lee, Sae Hwan Lee, Young Hyun Jung et al.. Frontiers in Aging Neuroscience, 2026-03-11
Topic: Brain proteins, microglia and lab models
Introduction Liver–metabolic stress and apolipoprotein E (APOE) ε4 are implicated in late-life cognitive vulnerability, yet how hepatic–metabolic indices relate to cognition and amyloid burden and whether these associations vary by APOE ε4 allele dose remains unclear. We examined liver–metabolic indices in relation to cognition and amyloid PET SUVR and tested effect modification by APOE ε4. Methods We analyzed baseline data from the Dementia Platform Korea Trial-Ready Registry (DPK-TRR). Primary multivariable analyses used complete cases for outcomes and covariates ( n = 507); amyloid PET analyses used the PET subset ( n = 496). Exposures included the triglyceride–glucose (TyG) index, AST/ALT ratio, and Fibrosis-4 (FIB-4) stage (low/intermediate/high). APOE ε4 was modeled as allele dose (0/1/2). Multivariable linear regression evaluated associations with global cognition (MMSE), selected domain outcomes, and amyloid PET SUVR, including FIB-4 stage × APOE ε4 dose interaction terms, adjusted for age, sex, education, hypertension, diabetes, and dyslipidemia. Results Higher TyG index and AST/ALT ratio were associated with lower MMSE scores (TyG: β = −1.13, 95% CI − 2.11 to −0.16; p = 0.022; AST/ALT: β = −1.40, 95% CI − 2.10 to −0.39; p = 0.007) and with memory performance on CERAD delayed recall (TyG: β = −0.29, 95% CI − 0.52 to −0.06; p = 0.012), whereas neither marker showed a clear association with amyloid PET SUVR. The association between FIB-4 stage and cognition differed by APOE ε4, showing a cross-over pattern across fibrosis stages: APOE ε4–associated differences were attenuated and reversed at intermediate/high FIB-4 compared with low FIB-4. In the amyloid PET subset, APOE ε4 group differences in SUVR were not prominent at low FIB-4, but tended to diverge at high FIB-4 with higher SUVR in groups with greater ε4 burden. Conclusion Routine liver–metabolic indices were associated with cognitive performance, while FIB-4 stage showed effect modification by APOE ε4 in relation to both cognition and amyloid PET SUVR. These findings support heterogeneity in liver–metabolic and genetic contributions to late-life cognitive vulnerability in a dementia trial-ready registry and motivate longitudinal studies to clarify temporal relationships.
Key findings
- Results Higher TyG index and AST/ALT ratio were associated with lower MMSE scores (TyG: β = −1.13, 95% CI − 2.11 to −0.16; p = 0.022; AST/ALT: β = −1.40, 95% CI − 2.10 to −0.39; p = 0.007) and with memory performance on CERAD delayed recall (TyG: β = −0.29, 95% CI − 0.52 to −0.06; p = 0.012), whereas neither marker showed a clear association with amyloid PET SUVR.
- The association between FIB-4 stage and cognition differed by APOE ε4, showing a cross-over pattern across fibrosis stages: APOE ε4–associated differences were attenuated and reversed at intermediate/high FIB-4 compared with low FIB-4.
- Conclusion Routine liver–metabolic indices were associated with cognitive performance, while FIB-4 stage showed effect modification by APOE ε4 in relation to both cognition and amyloid PET SUVR.
- These findings support heterogeneity in liver–metabolic and genetic contributions to late-life cognitive vulnerability in a dementia trial-ready registry and motivate longitudinal studies to clarify temporal relationships.
Why it matters
In a Korean registry, higher liver–metabolic markers (triglyceride–glucose index and AST/ALT ratio) were associated with lower MMSE scores and worse memory, and the link between fibrosis stage and cognition differed by APOE ε4 dose. These are cross-sectional associations that suggest metabolic factors may matter for risk, but they do not show that treating liver or metabolic problems prevents dementia.
Study details
- Study designlongitudinal study
- Participants507
- Evidence strengthModerate
How this study scored 51/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over 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 49 of the 96 points we could judge it on, which is 51 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in Aging Neuroscience) |
| Journal's citation record | 2 / 4 | Frontiers in Aging Neuroscience: journal h-index 174 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 507 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 4.7× 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 | OpenAlex's profile for last-listed author Sung-Hoon Yoon holds only 5 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 0 / 3 | Soonchunhyang University: institution h-index 265 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41890209) |
| Free to read | 2 / 2 | Free to read |
| Points | 49 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 49 of the 96 points we could judge it on is 51 out of 100. |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fnagi.2026.1773977
- PubMed: 41890209
- Original source →
- Free full text: Frontiers in Aging Neuroscience →
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
Ahn, Y. H., Kang, J. G., Choi, D., 김대진, Yang, C.-M., Lee, S. H., et al. (2026). Liver–metabolic stress, apolipoprotein E ε4, and cognition and amyloid burden: findings from the dementia platform Korea trial-ready registry. Frontiers in Aging Neuroscience. https://doi.org/10.3389/fnagi.2026.1773977
Vancouver
Ahn YH, Kang JG, Choi D, 김대진, Yang C.-M, Lee SH, et al. Liver–metabolic stress, apolipoprotein E ε4, and cognition and amyloid burden: findings from the dementia platform Korea trial-ready registry. Frontiers in Aging Neuroscience. 2026. doi:10.3389/fnagi.2026.1773977. PMID: 41890209.
BibTeX
@article{ahn2026-41890209,
author = {Ahn, Young Hyeon and Kang, Jin Gu and Choi, DaHyeon and 김대진 and Yang, Chan-Mo and Lee, S. H. and Lee, Sae Hwan and Jung, Young Hyun and others},
title = {{Liver–metabolic stress, apolipoprotein E ε4, and cognition and amyloid burden: findings from the dementia platform Korea trial-ready registry}},
journal = {Frontiers in Aging Neuroscience},
year = {2026},
doi = {10.3389/fnagi.2026.1773977},
pmid = {41890209},
url = {https://doi.org/10.3389/fnagi.2026.1773977}
}
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