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Moderating role of triglycerides in the relationship between amyloid-β, hippocampal atrophy, and cognitive decline in mild cognitive impairment and early Alzheimer’s disease
Ji‐Woo Seok, Kahye Kim, Soonjo Hwang, Kun Ho Lee, Jaeuk U. Kim. Frontiers in Aging Neuroscience, 2025-08-22
Topic: Amyloid, tau and blood-test diagnosis
Introduction The role of triglycerides in Alzheimer’s disease dementia (ADD) progression remains unclear. This study aimed to investigate how triglyceride levels influence the relationship between amyloid-beta (Aβ) deposition, hippocampal atrophy, and cognitive decline in individuals with mild cognitive impairment (MCI) and early-stage ADD. Methods A total 188 older adults (170 with MCI, 18 with early ADD) from the Gwangju Alzheimer’s Disease and Related cohort underwent amyloid PET and structural magnetic resonance imaging. Cognitive decline was assessed using the Korean version of the Mini-Mental State Examination (K-MMSE). A moderated mediation model (PROCESS model 7 with 10,000 bootstrap samples) was applied to examine whether hippocampal atrophy mediated the effect of Aβ on cognitive decline and whether this effect varied by triglyceride levels. Results The indirect effect of Aβ deposition on cognitive decline through hippocampal atrophy was significant (bootstrap 95% CI: −0.39 to −0.08), while the direct effect was not. This suggests that hippocampal atrophy plays a substantial mediating role in the pathway from Aβ burden to cognitive decline, although the indirect path accounted for approximately 49% of the total effect, indicating the possibility of other unexplored mechanisms. Furthermore, moderated mediation analysis revealed that triglyceride levels significantly moderated the effect of Aβ deposition on hippocampal volume (p < 0.05), with higher triglyceride levels amplifying the negative impact of Aβ deposition on hippocampal atrophy. Discussion These findings highlight hippocampal atrophy as a key pathway linking Aβ burden to cognitive impairment. Moreover, higher triglyceride levels may exacerbate Aβ-related neurodegeneration in individuals with MCI and early-stage ADD. Metabolic risk factors, such as triglycerides, may play an important role in strategies to prevent or delay cognitive decline in older adults with MCI and early ADD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Seok, J., Kim, K., Hwang, S., Lee, K. H., & Kim, J. U. (2025). Moderating role of triglycerides in the relationship between amyloid-β, hippocampal atrophy, and cognitive decline in mild cognitive impairment and early Alzheimer’s disease. Frontiers in Aging Neuroscience. https://doi.org/10.3389/fnagi.2025.1592341
Vancouver
Seok J, Kim K, Hwang S, Lee KH, Kim JU. Moderating role of triglycerides in the relationship between amyloid-β, hippocampal atrophy, and cognitive decline in mild cognitive impairment and early Alzheimer’s disease. Frontiers in Aging Neuroscience. 2025. doi:10.3389/fnagi.2025.1592341. PMID: 40918735.
BibTeX
@article{seok2025-40918735,
author = {Seok, Ji‐Woo and Kim, Kahye and Hwang, Soonjo and Lee, Kun Ho and Kim, Jaeuk U.},
title = {{Moderating role of triglycerides in the relationship between amyloid-β, hippocampal atrophy, and cognitive decline in mild cognitive impairment and early Alzheimer’s disease}},
journal = {Frontiers in Aging Neuroscience},
year = {2025},
doi = {10.3389/fnagi.2025.1592341},
pmid = {40918735},
url = {https://doi.org/10.3389/fnagi.2025.1592341}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Results The indirect effect of Aβ deposition on cognitive decline through hippocampal atrophy was significant (bootstrap 95% CI: −0.39 to −0.08), while the direct effect was not.
- This suggests that hippocampal atrophy plays a substantial mediating role in the pathway from Aβ burden to cognitive decline, although the indirect path accounted for approximately 49% of the total effect, indicating the possibility of other unexplored mechanisms.
- Furthermore, moderated mediation analysis revealed that triglyceride levels significantly moderated the effect of Aβ deposition on hippocampal volume (p < 0.05), with higher triglyceride levels amplifying the negative impact of Aβ deposition on hippocampal atrophy.
- Discussion These findings highlight hippocampal atrophy as a key pathway linking Aβ burden to cognitive impairment.
Why it matters
In people with mild cognitive impairment and early Alzheimer's disease, hippocampal atrophy mediated the link between amyloid-beta deposition and cognitive decline, and triglyceride levels moderated this relationship. This describes how a blood fat may influence the disease pathway rather than testing a treatment.
Study details
- Evidence strengthModerate
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| 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 | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.9× 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 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jaeuk U. Kim: h-index 23 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | University of Nebraska Medical Center: institution h-index 666 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40918735) |
| Free to read | 2 / 2 | Free to read |
| Total | 39 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fnagi.2025.1592341
- PubMed: 40918735
- 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).
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