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High Body Mass Index as a Causal Risk Factor for Vascular-Related Dementia: A Mendelian Randomization Study
Liv Tybjærg Nordestgaard, Jiao Luo, Frida Emanuelsson, Genevieve M Leyden, Eleanor C. M. Sanderson, George Davey Smith, Mette Christoffersen, Shoaib Afzal et al.. The Journal of Clinical Endocrinology & Metabolism, 2025-12-16
Topic: Risk, prevention and care in population studies
In a meta-analysis of 2 one-sample MR studies, the odds ratio (OR) for 1-SD higher BMI in predicting vascular-related dementia was 1.63 (95% CI, 1.13-2.35). In a two-sample MR study, the OR for vascular-related dementia per 1-SD higher BMI was 1.54 (1.10-2.16) using the inverse-variance weighted, 1.87 (1.22-2.85) using the weighted median, and 1.98 (1.21-3.22) using the weighted mode methods. Results from MR analyses including extended numbers of genetic variants were directionally consistent. Finally, systolic blood pressure mediated 18% (95% CI, 10%-61%) and diastolic blood pressure mediated 25% (13%-75%) of the genetic effect of BMI on vascular-related dementia. Observationally (U-shaped) and genetically (linearly), high BMI is associated with a higher risk of vascular-related dementia, an association partly mediated through high blood pressure. This suggests that high BMI and high blood pressure are important modifiable risk factors for dementia prevention.
Key findings
- In a meta-analysis of 2 one-sample MR studies, the odds ratio (OR) for 1-SD higher BMI in predicting vascular-related dementia was 1.63 (95% CI, 1.13-2.35).
- In a two-sample MR study, the OR for vascular-related dementia per 1-SD higher BMI was 1.54 (1.10-2.16) using the inverse-variance weighted, 1.87 (1.22-2.85) using the weighted median, and 1.98 (1.21-3.22) using the weighted mode methods.
- Results from MR analyses including extended numbers of genetic variants were directionally consistent.
- Finally, systolic blood pressure mediated 18% (95% CI, 10%-61%) and diastolic blood pressure mediated 25% (13%-75%) of the genetic effect of BMI on vascular-related dementia.
- Observationally (U-shaped) and genetically (linearly), high BMI is associated with a higher risk of vascular-related dementia, an association partly mediated through high blood pressure.
Why it matters
This Mendelian randomization study found that higher body mass index was associated with a higher risk of vascular-related dementia, partly mediated through high blood pressure. The authors conclude that high BMI and high blood pressure are important modifiable risk factors for dementia prevention.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 57/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of Clinical Endocrinology & Metabolism) |
| Journal's citation record | 3 / 4 | The Journal of Clinical Endocrinology & Metabolism: journal h-index 490 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” 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 | A review of other studies — randomisation is not credited here |
| 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 2.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Ruth Frikke‐Schmidt: h-index 65 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Copenhagen: institution h-index 1,378 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41568975) |
| Free to read | 2 / 2 | Free to read |
| Total | 57 / 100 | — |
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Read the original
- DOI: 10.1210/clinem/dgaf662
- PubMed: 41568975
- Original source →
- Free full text: Explore Bristol Research →
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
Nordestgaard, L. T., Luo, J., Emanuelsson, F., Leyden, G. M., Sanderson, E. C. M., Smith, G. D., et al. (2025). High Body Mass Index as a Causal Risk Factor for Vascular-Related Dementia: A Mendelian Randomization Study. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/clinem/dgaf662
Vancouver
Nordestgaard LT, Luo J, Emanuelsson F, Leyden GM, Sanderson ECM, Smith GD, et al. High Body Mass Index as a Causal Risk Factor for Vascular-Related Dementia: A Mendelian Randomization Study. The Journal of Clinical Endocrinology & Metabolism. 2025. doi:10.1210/clinem/dgaf662. PMID: 41568975.
BibTeX
@article{nordestgaard2025-41568975,
author = {Nordestgaard, Liv Tybjærg and Luo, Jiao and Emanuelsson, Frida and Leyden, Genevieve M and Sanderson, Eleanor C. M. and Smith, George Davey and Christoffersen, Mette and Afzal, Shoaib and others},
title = {{High Body Mass Index as a Causal Risk Factor for Vascular-Related Dementia: A Mendelian Randomization Study}},
journal = {The Journal of Clinical Endocrinology \& Metabolism},
year = {2025},
doi = {10.1210/clinem/dgaf662},
pmid = {41568975},
url = {https://doi.org/10.1210/clinem/dgaf662}
}
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