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Bidirectional relationship between epigenetic age and stroke, dementia, and late-life depression
Cyprien A. Rivier, Natalia Szejko, Daniela B. Renedo, Santiago Clocchiatti‐Tuozzo, Shufan Huo, Adam de Havenon, Hongyu Zhao, Thomas M. Gill et al.. Nature Communications, 2025-02-01
Topic: Risk, prevention and care in population studies
Chronological age is an imperfect estimate of molecular aging. Epigenetic age, derived from DNA methylation data, provides a more nuanced representation of aging-related biological processes. We examine the bidirectional relationship between epigenetic age and brain health events (stroke, dementia, late-life depression) using data from 4,018 participants. Participants with a prior brain health event are 4% epigenetically older (β = 0.04, SE = 0.01), indicating these conditions are associated with accelerated aging beyond that captured by chronological age. Additionally, a one standard deviation increase in epigenetic age is associated with 70% higher odds of experiencing a brain health event in the next four years (OR = 1.70, 95% CI = 1.16–2.50), suggesting epigenetic age acceleration is not just a consequence but also a predictor of poor brain health. Mendelian Randomization analyses replicate these findings, supporting their causal nature. Our results support using epigenetic age as a biomarker to evaluate interventions aimed at preventing and promoting recovery after brain health events. Here, the authors examine the bidirectional relationship between epigenetic age and brain health events, suggesting that stroke and dementia accelerate our epigenetic age, while an accelerated epigenetic age increases the risk of these conditions.
Key findings
- Participants with a prior brain health event are 4% epigenetically older (β = 0.04, SE = 0.01), indicating these conditions are associated with accelerated aging beyond that captured by chronological age.
- Additionally, a one standard deviation increase in epigenetic age is associated with 70% higher odds of experiencing a brain health event in the next four years (OR = 1.70, 95% CI = 1.16–2.50), suggesting epigenetic age acceleration is not just a consequence but also a predictor of poor brain health
- Mendelian Randomization analyses replicate these findings, supporting their causal nature.
- Our results support using epigenetic age as a biomarker to evaluate interventions aimed at preventing and promoting recovery after brain health events.
- Here, the authors examine the bidirectional relationship between epigenetic age and brain health events, suggesting that stroke and dementia accelerate our epigenetic age, while an accelerated epigenetic age increases the risk of these conditions.
Why it matters
In 4,018 participants, having a prior stroke, dementia, or late-life depression was linked to being epigenetically older, and greater epigenetic age predicted higher odds of a brain health event in the next four years. The authors suggest epigenetic age could be used as a biomarker to evaluate interventions aimed at preventing these conditions and promoting recovery.
Study details
- Participants4,018
- Effect sizeOR = 1.70
- Evidence strengthLow
How this study scored 55/100
Published in a leading specialty journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature Communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (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 | 3 / 4 | 4,018 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 2 / 7 | Cited 13 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 3.4× 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 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Guido J. Falcone: h-index 55 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Yale University: institution h-index 1,927 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39893209) |
| Free to read | 2 / 2 | Free to read |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41467-024-54721-0
- PubMed: 39893209
- Original source →
- Free full text: Nature Communications →
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
Rivier, C. A., Szejko, N., Renedo, D. B., Clocchiatti‐Tuozzo, S., Huo, S., de Havenon, A., et al. (2025). Bidirectional relationship between epigenetic age and stroke, dementia, and late-life depression. Nature Communications. https://doi.org/10.1038/s41467-024-54721-0
Vancouver
Rivier CA, Szejko N, Renedo DB, Clocchiatti‐Tuozzo S, Huo S, de Havenon A, et al. Bidirectional relationship between epigenetic age and stroke, dementia, and late-life depression. Nature Communications. 2025. doi:10.1038/s41467-024-54721-0. PMID: 39893209.
BibTeX
@article{rivier2025-39893209,
author = {Rivier, Cyprien A. and Szejko, Natalia and Renedo, Daniela B. and Clocchiatti‐Tuozzo, Santiago and Huo, Shufan and de Havenon, Adam and Zhao, Hongyu and Gill, Thomas M. and others},
title = {{Bidirectional relationship between epigenetic age and stroke, dementia, and late-life depression}},
journal = {Nature Communications},
year = {2025},
doi = {10.1038/s41467-024-54721-0},
pmid = {39893209},
url = {https://doi.org/10.1038/s41467-024-54721-0}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.