Topic: Risk, prevention and care in population studies
Among 4392 participants (mean [SD] age, 68.2 [7.8] years; 2359 [53.7%] women), 723 (16.5%) were APOE ε4 heterozygotes and 33 (0.8%) were APOE ε4 homozygotes. Over a mean (SD) follow-up of 6.3 (0.9) years, the mean (SD) annual MMSE decline was -0.2 (0.5). APOE ε4 carriage was associated with a significantly steeper quadratic age-associated decline in MMSE scores compared with noncarriers (estimate, -0.005; SE, 0.001; P = .001). This association was strongest among homozygotes (estimate, -0.017; SE, 0.008; P = .03), with MMSE trajectories diverging after approximately age 70 years. In contrast, PRS_ADnapoe scores were not associated with MMSE decline. Sensitivity analyses restricted to participants with 2-wave data and adjusted with inverse probability of censoring weighting confirmed these findings. Conclusions and Relevance: In this cohort study of middle-aged and older adults in Taiwan, APOE ε4 carriage, particularly homozygosity, was associated with accelerated age-related cognitive decline detectable after age 70 years, whereas non-APOE polygenic risk was not associated with cognitive decline over the current follow-up. These results highlight the potential utility of early genetic risk awareness and support consideration of targeted preventive strategies for APOE ε4 carriers.
Key findings
- Among 4392 participants (mean [SD] age, 68.2 [7.8] years; 2359 [53.7%] women), 723 (16.5%) were APOE ε4 heterozygotes and 33 (0.8%) were APOE ε4 homozygotes.
- Over a mean (SD) follow-up of 6.3 (0.9) years, the mean (SD) annual MMSE decline was -0.2 (0.5).
- APOE ε4 carriage was associated with a significantly steeper quadratic age-associated decline in MMSE scores compared with noncarriers (estimate, -0.005; SE, 0.001; P = .001).
- This association was strongest among homozygotes (estimate, -0.017; SE, 0.008; P = .03), with MMSE trajectories diverging after approximately age 70 years.
- In contrast, PRS_ADnapoe scores were not associated with MMSE decline.
Why it matters
In this cohort, carrying APOE ε4, especially having two copies, was linked to faster age-related cognitive decline that became detectable after about age 70. The authors suggest this supports early genetic risk awareness and consideration of targeted preventive strategies for APOE ε4 carriers, though no specific prevention was tested.
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Study details
- Study designcohort study
- Participants4,392
- Effect size53.7%; 16.5%; 0.8%
- Evidence strengthModerate
How this study scored 58/100
Published in a leading specialty 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 | 9 / 10 | Tier 2 — leading specialty journal (JAMA Network Open) |
| Journal's citation record | 2 / 4 | JAMA Network Open: journal h-index 235 (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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 4,392 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 5 / 6 | Cited 23.7× 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 | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 0 / 4 | Last-listed author Wei J. Chen: h-index 3 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | National Health Research Institutes: institution h-index 346 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41790466) |
| Free to read | 2 / 2 | Free to read |
| Total | 58 / 100 | — |
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Read the original
- DOI: 10.1001/jamanetworkopen.2026.0853
- PubMed: 41790466
- Original source →
- Free full text: JAMA Network Open →
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
Chung, Y.-C. E., Chung, R.-H., Hsu, C.-C., Liu, Y.-L., Lai, R.-H., Hung, W.-J., et al. (2026). APOE ε4 and Accelerated Cognitive Decline Among Cognitively Healthy Middle-Aged and Older Adults. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2026.0853
Vancouver
Chung Y.-CE, Chung R.-H, Hsu C.-C, Liu Y.-L, Lai R.-H, Hung W.-J, et al. APOE ε4 and Accelerated Cognitive Decline Among Cognitively Healthy Middle-Aged and Older Adults. JAMA Network Open. 2026. doi:10.1001/jamanetworkopen.2026.0853. PMID: 41790466.
BibTeX
@article{chung2026-41790466,
author = {Chung, Yu-Chu Ella and Chung, Ren-Hua and Hsu, Chih-Cheng and Liu, Yu-Li and Lai, Rai-Hua and Hung, Wen-Jiu and Wu, Ray-Chin and Jiang, Yun‐Jin and others},
title = {{APOE ε4 and Accelerated Cognitive Decline Among Cognitively Healthy Middle-Aged and Older Adults}},
journal = {JAMA Network Open},
year = {2026},
doi = {10.1001/jamanetworkopen.2026.0853},
pmid = {41790466},
url = {https://doi.org/10.1001/jamanetworkopen.2026.0853}
}
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