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Mediation Analyses Link Cardiometabolic Factors and Liver Fat With White Matter Hyperintensities and Cognitive Performance: A UK Biobank Study
Daniel E. Askeland-Gjerde, Lars Tjelta Westlye, Patrik U. Andersson, Max Korbmacher, Ann‐Marie G. de Lange, Dennis van der Meer, Olav Bjerkehagen Smeland, Sigrun Halvorsen et al.. Biological Psychiatry Global Open Science, 2025-03-20
Topic: Brain proteins, microglia and lab models
Background Liver fat is associated with cardiometabolic disease, cerebrovascular disease , and dementia. Cerebrovascular disease, most often cerebral small vessel disease, identified by magnetic resonance imaging as white matter hyperintensities (WMHs) often contributes to dementia. However, liver fat’s role in the relationship between cardiometabolic risk , WMHs, and cognitive performance is unclear. Methods In the UK Biobank cohort ( N = 32,461, 52.6% female; mean age 64.2 ± 7.7 years; n = 23,354 in the cognitive performance subsample), we used linear regression to investigate associations between cardiometabolic factors measured at baseline and liver fat, WMHs, and cognitive performance measured at follow-up, which was 9.3 ± 2.0 years later on average. We used structural equation modeling to investigate whether liver fat mediated associations between cardiometabolic factors and WMHs and whether WMHs mediated associations between liver fat and cognitive performance. Results Nearly all cardiometabolic factors were significantly associated with liver fat (| r | range = 0.03–0.41, p = 3.4 × 10 −8 to 0) and WMHs (| r | = 0.04–0.15, p = 5.8 × 10 −13 to 7.0 × 10 −159 ) in regression models. Liver fat was associated with WMHs ( r = 0.11, p = 4.3 × 10 −82 ) and cognitive performance ( r = −0.03, p = 1.6 × 10 −7 ). Liver fat mediated the associations between cardiometabolic factors and WMHs (|β mediation | = 0.003–0.027, p mediation = 1.9 × 10 −8 to 0), and WMHs mediated the associations between liver fat and cognitive performance (β mediation = −0.01, p mediation = 0). Conclusions Our findings indicate that liver fat mediates associations between cardiometabolic factors and WMHs and that WMHs mediate the association between liver fat and cognitive performance. This suggests that liver fat may be important for understanding the effects of cardiometabolic factors on cerebrovascular disease and cognitive function. Experimental studies are warranted to determine relevant targets for preventing vascular-driven cognitive impairment .
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APA 7th
Askeland-Gjerde, D. E., Westlye, L. T., Andersson, P. U., Korbmacher, M., de Lange, A. G., van der Meer, D., et al. (2025). Mediation Analyses Link Cardiometabolic Factors and Liver Fat With White Matter Hyperintensities and Cognitive Performance: A UK Biobank Study. Biological Psychiatry Global Open Science. https://doi.org/10.1016/j.bpsgos.2025.100488
Vancouver
Askeland-Gjerde DE, Westlye LT, Andersson PU, Korbmacher M, de Lange AG, van der Meer D, et al. Mediation Analyses Link Cardiometabolic Factors and Liver Fat With White Matter Hyperintensities and Cognitive Performance: A UK Biobank Study. Biological Psychiatry Global Open Science. 2025. doi:10.1016/j.bpsgos.2025.100488. PMID: 40330223.
BibTeX
@article{askelandgjerde2025-40330223,
author = {Askeland-Gjerde, Daniel E. and Westlye, Lars Tjelta and Andersson, Patrik U. and Korbmacher, Max and de Lange, Ann‐Marie G. and van der Meer, Dennis and Smeland, Olav Bjerkehagen and Halvorsen, Sigrun and others},
title = {{Mediation Analyses Link Cardiometabolic Factors and Liver Fat With White Matter Hyperintensities and Cognitive Performance: A UK Biobank Study}},
journal = {Biological Psychiatry Global Open Science},
year = {2025},
doi = {10.1016/j.bpsgos.2025.100488},
pmid = {40330223},
url = {https://doi.org/10.1016/j.bpsgos.2025.100488}
}
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
- Background Liver fat is associated with cardiometabolic disease, cerebrovascular disease , and dementia.
- Results Nearly all cardiometabolic factors were significantly associated with liver fat (| r | range = 0.03–0.41, p = 3.4 × 10 −8 to 0) and WMHs (| r | = 0.04–0.15, p = 5.8 × 10 −13 to 7.0 × 10 −159 ) in regression models.
- Liver fat was associated with WMHs ( r = 0.11, p = 4.3 × 10 −82 ) and cognitive performance ( r = −0.03, p = 1.6 × 10 −7 ).
- Conclusions Our findings indicate that liver fat mediates associations between cardiometabolic factors and WMHs and that WMHs mediate the association between liver fat and cognitive performance.
- This suggests that liver fat may be important for understanding the effects of cardiometabolic factors on cerebrovascular disease and cognitive function.
Why it matters
In this UK Biobank analysis, liver fat was linked to white matter hyperintensities and to cognitive performance, and it mediated the link between cardiometabolic factors and these brain measures. This points to cardiometabolic and liver health as possible targets for reducing small vessel disease that can contribute to dementia, though the study shows associations, not cause and effect.
Study details
- Participants32,461
- Effect size52.6%
- Evidence strengthModerate
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biological Psychiatry Global Open Science) |
| Journal's citation record | 0 / 4 | Biological Psychiatry Global Open Science: journal h-index 32 (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 | 4 / 4 | 32,461 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.3× 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 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Tiril Pedersen Gurholt: h-index 23 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40330223) |
| Free to read | 2 / 2 | Free to read |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.bpsgos.2025.100488
- PubMed: 40330223
- Original source →
- Free full text: Biological Psychiatry Global Open Science →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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