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Proteomics-based aging clocks in midlife or late-life and their associated risk of dementia
Sanaz Sedaghat, Saeun Park, Rob F. Walker, Shuo Wang, Jialing Liu, Timothy M. Hughes, Behnam Sabayan, Weihong Tang et al.. Communications Medicine, 2025-08-14
Topic: Risk, prevention and care in population studies
We investigated whether a discrepancy between chronological and biological age in midlife and late-life is associated with cognition and dementia risk. In ARIC, every five years, PAA is associated with lower global cognition: difference: −0.11, 95% confidence interval[CI]: −0.16, −0.06) using midlife PAA and difference: −0.17, CI: −0.23, −0.12 using late-life PAA. Midlife PAA is associated with higher dementia risk (hazard ratio[HR]: 1.20 [CI: 1.04, 1.36]) and more prominently when using late-life PAA (HR: 2.14 [CI:1.67, 2.73]). Similar findings are observed in MESA: PAA is associated with lower global cognitive function (difference: −0.08 [CI: −0.14, −0.03]) and higher dementia risk (HR:1.23 [CI: 1.04, 1.46]). Accelerated biological age is associated with lower cognition and a higher risk of dementia in midlife and more prominently in late life. We studied whether people who age faster biologically than their calendar age have worse cognitive function and a higher risk of dementia. We found that when individuals’ biological age was higher than their calendar age, they tended to have poorer cognitive function and were more likely to develop dementia. They find that the PACs are associated with lower cognition and a higher risk of dementia in midlife and more prominently in late-life.
Key findings
- We investigated whether a discrepancy between chronological and biological age in midlife and late-life is associated with cognition and dementia risk.
- In ARIC, every five years, PAA is associated with lower global cognition: difference: −0.11, 95% confidence interval[CI]: −0.16, −0.06) using midlife PAA and difference: −0.17, CI: −0.23, −0.12 using late-life PAA.
- Midlife PAA is associated with higher dementia risk (hazard ratio[HR]: 1.20 [CI: 1.04, 1.36]) and more prominently when using late-life PAA (HR: 2.14 [CI:1.67, 2.73]).
- Similar findings are observed in MESA: PAA is associated with lower global cognitive function (difference: −0.08 [CI: −0.14, −0.03]) and higher dementia risk (HR:1.23 [CI: 1.04, 1.46]).
- Accelerated biological age is associated with lower cognition and a higher risk of dementia in midlife and more prominently in late life.
Why it matters
In the ARIC and MESA cohorts, accelerated biological age was associated with lower cognition and higher dementia risk in midlife and more prominently in late life. This suggests that proteomics-based aging clocks may help identify people at higher risk, but it is a risk association rather than a treatment or cure.
Study details
- Study designcohort study
- Participants11,758
- Effect sizeHR: 2.14; HR:1.23
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Communications Medicine) |
| Journal's citation record | 0 / 4 | Communications Medicine: journal h-index 55 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over 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 | 4 / 4 | 11,758 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 | 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 Anna E. Prizment: h-index 38 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 15 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40813726) |
| Free to read | 2 / 2 | Free to read |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s43856-025-01096-y
- PubMed: 40813726
- Original source →
- Free full text: Communications Medicine →
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
Sedaghat, S., Park, S., Walker, R. F., Wang, S., Liu, J., Hughes, T. M., et al. (2025). Proteomics-based aging clocks in midlife or late-life and their associated risk of dementia. Communications Medicine. https://doi.org/10.1038/s43856-025-01096-y
Vancouver
Sedaghat S, Park S, Walker RF, Wang S, Liu J, Hughes TM, et al. Proteomics-based aging clocks in midlife or late-life and their associated risk of dementia. Communications Medicine. 2025. doi:10.1038/s43856-025-01096-y. PMID: 40813726.
BibTeX
@article{sedaghat2025-40813726,
author = {Sedaghat, Sanaz and Park, Saeun and Walker, Rob F. and Wang, Shuo and Liu, Jialing and Hughes, Timothy M. and Sabayan, Behnam and Tang, Weihong and others},
title = {{Proteomics-based aging clocks in midlife or late-life and their associated risk of dementia}},
journal = {Communications Medicine},
year = {2025},
doi = {10.1038/s43856-025-01096-y},
pmid = {40813726},
url = {https://doi.org/10.1038/s43856-025-01096-y}
}
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