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Sustained fish intake and 21-year Alzheimer's disease risk: a target trial emulation
Zhao Y, Jacques PF, Lajous M, Sebastiani P, Ordovás JM. American Journal of Epidemiology, 2026-07-27
Topic: Amyloid, tau and blood-test diagnosis
Increasing oily fish intake has been proposed as a strategy for Alzheimer's disease (AD) prevention, but evidence for long-term benefit remains limited. Using observational data from 2012 cognitively healthy adults in the Framingham Heart Study Offspring cohort, we emulated a target trial of seven isocaloric fish intake strategies to estimate 21-year AD risk. We modeled repeated measures of diet and adjusted for pre-baseline diet, baseline covariates, and time-varying confounding using the parametric g-formula. The estimated 21-year AD risk ranged from 10.33% (95% confidence interval [CI]: 8.41%, 12.92%) under no fish intake to 9.98% (95% CI, 6.64%, 13.31%) under ≥ 3 servings/week. Risk ratios relative to no intervention were close to one and risk differences were close to zero across all strategies. Substituting fish for meat yielded similar results. We observed no clear long-term protective effect of sustained fish intake on AD risk, though exploratory analyses suggested a possible protective effect among older participants during earlier follow-up, warranting further investigation. This study illustrates the use of target trial emulation to estimate long-term dietary effects while accounting for time-varying confounding and competing risks in nutritional epidemiology.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zhao, Y., Jacques, P. F., Lajous, M., Sebastiani, P., & Ordovás, J. M. (2026). Sustained fish intake and 21-year Alzheimer's disease risk: a target trial emulation. American Journal of Epidemiology. https://doi.org/10.1093/aje/kwag140
Vancouver
Zhao Y, Jacques PF, Lajous M, Sebastiani P, Ordovás JM. Sustained fish intake and 21-year Alzheimer's disease risk: a target trial emulation. American Journal of Epidemiology. 2026. doi:10.1093/aje/kwag140. PMID: 42506897.
BibTeX
@article{zhao2026-42506897,
author = {Zhao, Y. and Jacques, P. F. and Lajous, M. and Sebastiani, P. and Ordovás, J. M.},
title = {{Sustained fish intake and 21-year Alzheimer's disease risk: a target trial emulation}},
journal = {American Journal of Epidemiology},
year = {2026},
doi = {10.1093/aje/kwag140},
pmid = {42506897},
url = {https://doi.org/10.1093/aje/kwag140}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Substituting fish for meat yielded similar results.
- We observed no clear long-term protective effect of sustained fish intake on AD risk, though exploratory analyses suggested a possible protective effect among older participants during earlier follow-up, warranting further investigation.
Why it matters
This analysis of long-term fish intake found no clear protective effect on Alzheimer's disease risk over 21 years. It is observational, and the authors say the possible benefit seen in older participants during earlier follow-up needs more study.
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Study details
- Study designcohort
- Participants2,012
- Effect size21-year Alzheimer's risk 10.33% (no fish) vs 9.98% (3+ servings/week); risk ratios near 1
- Evidence strengthNull-result
Limitations
Single, mostly white cohort; wide confidence intervals; exploratory hint of benefit in older participants early in follow-up not confirmed.
How this study scored 52/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for randomized / blinded because the record does not state it. We have no data on senior author's track record and free to read, so those were left out: it earned 49 of the 94 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (American Journal of Epidemiology) |
| Journal's citation record | 3 / 4 | American Journal of Epidemiology: journal h-index 416 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “null-result” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 2,012 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) |
| Randomized / blinded | 0 / 2 | No randomization 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 | 0 / 6 | Cited 0.0× 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 | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Barro Ordovas holds only 5 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 1 / 3 | Tufts University: institution h-index 1,045 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42506897) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 49 / 94 | Scored on 18 of 20 parts. We have no data for the rest, so they are left out: 49 of the 94 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
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