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DNA methylation age from peripheral blood predicts progression to Alzheimer’s disease, white matter disease burden, and cortical atrophy
Luke W. Bonham, Daniel W. Sirkis, Alina P.S. Pang, Leo P. Sugrue, Hernando A Santamaría‐García, Agustín M. Ibáñez, Bruce Leonard Miller, Jennifer S. Yokoyama et al.. npj Dementia, 2025-05-27
Topic: Brain proteins, microglia and lab models
Cross-sectional studies suggest a limited relationship between accelerated epigenetic aging derived from epigenetic clocks, and Alzheimer's disease (AD) pathophysiology or risk. However, most prior analyses have not utilized longitudinal analyses or whole-brain neuroimaging biomarkers of AD. Herein, we employed longitudinal modeling and structural neuroimaging analyses to test the hypothesis that accelerated epigenetic aging would predict AD progression. Using survival analyses, we found that two second-generation epigenetic clocks, DNAmPhenoAge and DNAmGrimAge, predicted progression from cognitively normal aging to mild cognitive impairment or AD and worse longitudinal cognitive outcomes. Epigenetic age was also strongly associated with cortical thinning in AD-relevant regions and white matter disease burden. Thus, in contrast to earlier work suggesting limited applicability of blood-based epigenetic clocks in AD, our novel analytic framework suggests that second-generation epigenetic clocks have broad utility and may represent promising predictors of AD risk and pathophysiology.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Bonham, L. W., Sirkis, D. W., Pang, A. P., Sugrue, L. P., Santamaría‐García, H. A., Ibáñez, A. M., et al. (2025). DNA methylation age from peripheral blood predicts progression to Alzheimer’s disease, white matter disease burden, and cortical atrophy. npj Dementia. https://doi.org/10.1038/s44400-025-00007-1
Vancouver
Bonham LW, Sirkis DW, Pang AP, Sugrue LP, Santamaría‐García HA, Ibáñez AM, et al. DNA methylation age from peripheral blood predicts progression to Alzheimer’s disease, white matter disease burden, and cortical atrophy. npj Dementia. 2025. doi:10.1038/s44400-025-00007-1. PMID: 40443531.
BibTeX
@article{bonham2025-40443531,
author = {Bonham, Luke W. and Sirkis, Daniel W. and Pang, Alina P.S. and Sugrue, Leo P. and Santamaría‐García, Hernando A and Ibáñez, Agustín M. and Miller, Bruce Leonard and Yokoyama, Jennifer S. and others},
title = {{DNA methylation age from peripheral blood predicts progression to Alzheimer’s disease, white matter disease burden, and cortical atrophy}},
journal = {npj Dementia},
year = {2025},
doi = {10.1038/s44400-025-00007-1},
pmid = {40443531},
url = {https://doi.org/10.1038/s44400-025-00007-1}
}
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
- Using survival analyses, we found that two second-generation epigenetic clocks, DNAmPhenoAge and DNAmGrimAge, predicted progression from cognitively normal aging to mild cognitive impairment or AD and worse longitudinal cognitive outcomes.
- Epigenetic age was also strongly associated with cortical thinning in AD-relevant regions and white matter disease burden.
- Thus, in contrast to earlier work suggesting limited applicability of blood-based epigenetic clocks in AD, our novel analytic framework suggests that second-generation epigenetic clocks have broad utility and may represent promising predictors of AD risk and pathophysiology.
Why it matters
Two blood-based epigenetic clocks, DNAmPhenoAge and DNAmGrimAge, predicted progression from cognitively normal aging to mild cognitive impairment or Alzheimer's disease and were linked to cortical thinning and white matter disease burden. This is not a treatment or cure, but it suggests these blood measures may help predict risk and track disease-related brain changes.
Study details
- Study designcross-sectional
- Evidence strengthModerate
How this study scored 50/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for sample size, effect reported, studied in people 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 48 of the 96 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (npj Dementia) |
| Journal's citation record | 0 / 4 | Npj Dementia: journal h-index 10 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in 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 | 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 | 3 / 7 | Cited 16 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 10.2× 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 | 2 / 4 | Cited 16 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40443531) |
| Free to read | 2 / 2 | Free to read |
| Points | 48 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 48 of the 96 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | — |
What each of these 20 components measures, and what this score is not →
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