Multi-trait Polygenic Profiling and Survival Free of Dementia and Disability: Results from the Health and Retirement Study
Tawaldemedhen, Y.; Clocchiatti-Tuozzo, S.; Rivier, C.; Huo, S.; Silberfeld, A.; D'Aoust, T.; Debette, S.; de Havenon et al.. medRxiv (preprint), 2026-09-11
Topic: Risk, prevention and care in population studies
ObjectiveTo determine whether a multi-trait polygenic profile for dementia is associated with dementia- and disability-free survival in middle-aged and older adults. BackgroundClinical trials of brain health and aging increasingly use holistic, patient-centered outcomes that capture overall health status. We hypothesized that adverse polygenic profiles for dementia would be associated with higher risk of dementia, disability, or death. Compared with a favorable polygenic profile, intermediate and poor profiles were associated with higher risk of the composite outcome (HR 1.14, 95% CI 1.07-1.21 and HR 1.43, 95% CI 1.26-1.63, respectively). The relative association was strongest for dementia; for poor versus favorable profiles, HRs were 1.58 (95% CI 1.21-2.05) for dementia, 1.43 (95% CI 1.14-1.79) for disability, and 1.33 (95% CI 1.15-1.54) for death. ConclusionsAdverse polygenic profiles for dementia were associated with higher composite risk of dementia, disability, or death in a large population-based cohort, with the strongest association observed for dementia. These findings support the potential value of polygenic profiling for risk stratification while highlighting limitations related to ancestry, generalizability, and clinical translation.
Key findings
- ObjectiveTo determine whether a multi-trait polygenic profile for dementia is associated with dementia- and disability-free survival in middle-aged and older adults.
- BackgroundClinical trials of brain health and aging increasingly use holistic, patient-centered outcomes that capture overall health status.
- We hypothesized that adverse polygenic profiles for dementia would be associated with higher risk of dementia, disability, or death.
- Compared with a favorable polygenic profile, intermediate and poor profiles were associated with higher risk of the composite outcome (HR 1.14, 95% CI 1.07-1.21 and HR 1.43, 95% CI 1.26-1.63, respectively).
- The relative association was strongest for dementia; for poor versus favorable profiles, HRs were 1.58 (95% CI 1.21-2.05) for dementia, 1.43 (95% CI 1.14-1.79) for disability, and 1.33 (95% CI 1.15-1.54) for death.
Why it matters
This study found that adverse polygenic profiles for dementia were associated with higher risk of dementia, disability, or death in a large population. It supports polygenic profiling for risk stratification but does not test any treatment, cure, or prevention.
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Study details
- Study designlongitudinal study
- Effect sizeHR 1.14; HR 1.43; HR 2.32
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 38 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for sample size, studied in people and randomised / blinded because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 36 of the 94 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv (preprint)) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 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 | 3 / 3 | Centre National de la Recherche Scientifique: institution h-index 2,511 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 2 countries |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 36 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 36 of the 94 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
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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
Tawaldemedhen, Y., Clocchiatti-Tuozzo, S., Rivier, C., Huo, S., Silberfeld, A., D'Aoust, T., et al. (2026). Multi-trait Polygenic Profiling and Survival Free of Dementia and Disability: Results from the Health and Retirement Study. medRxiv (preprint). https://doi.org/10.64898/2026.09.09.26362686
Vancouver
Tawaldemedhen Y, Clocchiatti-Tuozzo S, Rivier C, Huo S, Silberfeld A, D'Aoust T, et al. Multi-trait Polygenic Profiling and Survival Free of Dementia and Disability: Results from the Health and Retirement Study. medRxiv (preprint). 2026. doi:10.64898/2026.09.09.26362686.
BibTeX
@article{tawaldemedhen2026-e05c6a7d,
author = {Tawaldemedhen, Y. and Clocchiatti-Tuozzo, S. and Rivier, C. and Huo, S. and Silberfeld, A. and D'Aoust, T. and Debette, S. and Havenon, de and others},
title = {{Multi-trait Polygenic Profiling and Survival Free of Dementia and Disability: Results from the Health and Retirement Study}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.09.09.26362686},
url = {https://doi.org/10.64898/2026.09.09.26362686}
}
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