Impact of learning APOE genotype on cognitively unimpaired adults: a pre-screening cohort study of the Alzheimer's Prevention Initiative Generation Study 1
Langbaum JB, Bradbury AR, Egleston BL, McCarty Wood E, Langlois CM, Largent EA, Harkins K, Erickson CM, Stites SD, Oyen E, et al.. The Lancet Healthy Longevity, 2025-11-27
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Background The apolipoprotein E (APOE) gene is the best established genetic risk factor for Alzheimer's disease in later life, with the ε4 allele conferring higher risk. Disease-specific distress 2-7 days after disclosure increased more in homozygotes (2·25 [6·42]) than in heterozygotes (0·53 [5·08], p Interpretation In cognitively unimpaired, psychologically pre-screened adults, APOE disclosure by a trained health-care provider was generally safe and well tolerated, consistent with results from previous studies. To our knowledge, this is the largest study experience of APOE disclosure to date, especially for homozygotes, and is notable for the older age of participants compared with previous research. These results are timely and important given anticipated increases in APOE disclosure to guide clinical decision making once an Alzheimer's disease prevention treatment is approved for cognitively unimpaired adults or if patients' family members are interested in genetic testing. Results from this study may be useful to bolster clinical translatability of disclosure programmes.
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APA 7th
Langbaum, J. B., Bradbury, A. R., Egleston, B. L., McCarty Wood, E., Langlois, C. M., Largent, E. A., et al. (2025). Impact of learning APOE genotype on cognitively unimpaired adults: a pre-screening cohort study of the Alzheimer's Prevention Initiative Generation Study 1. The Lancet Healthy Longevity. https://doi.org/10.1016/j.lanhl.2025.100778
Vancouver
Langbaum JB, Bradbury AR, Egleston BL, McCarty Wood E, Langlois CM, Largent EA, et al. Impact of learning APOE genotype on cognitively unimpaired adults: a pre-screening cohort study of the Alzheimer's Prevention Initiative Generation Study 1. The Lancet Healthy Longevity. 2025. doi:10.1016/j.lanhl.2025.100778. PMID: 41319675.
BibTeX
@article{langbaum2025-41319675,
author = {Langbaum, J. B. and Bradbury, A. R. and Egleston, B. L. and McCarty Wood, E. and Langlois, C. M. and Largent, E. A. and Harkins, K. and Erickson, C. M. and Stites, S. D. and Oyen, E. and others},
title = {{Impact of learning APOE genotype on cognitively unimpaired adults: a pre-screening cohort study of the Alzheimer's Prevention Initiative Generation Study 1}},
journal = {The Lancet Healthy Longevity},
year = {2025},
doi = {10.1016/j.lanhl.2025.100778},
pmid = {41319675},
url = {https://doi.org/10.1016/j.lanhl.2025.100778}
}
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Key findings
- Background The apolipoprotein E (APOE) gene is the best established genetic risk factor for Alzheimer's disease in later life, with the ε4 allele conferring higher risk.
- Disease-specific distress 2-7 days after disclosure increased more in homozygotes (2·25 [6·42]) than in heterozygotes (0·53 [5·08], p<0·0001) and non-carriers (0·79 [4·95], p<0·0001).
- To our knowledge, this is the largest study experience of APOE disclosure to date, especially for homozygotes, and is notable for the older age of participants compared with previous research.
- These results are timely and important given anticipated increases in APOE disclosure to guide clinical decision making once an Alzheimer's disease prevention treatment is approved for cognitively unimpaired adults or if patients' family members are interested in genetic testing.
- Results from this study may be useful to bolster clinical translatability of disclosure programmes.
Why it matters
This study found that disclosing APOE genotype to cognitively unimpaired, psychologically pre-screened adults by a trained health-care provider was generally safe and well tolerated. Disease-specific distress 2-7 days after disclosure increased more in homozygotes than in heterozygotes, and the authors say the results may be useful for clinical disclosure programmes.
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Study details
- Study designcohort
- Participants9,496
- Effect sizeDisease-specific distress change at 2-7 days: +2.25 (homozygotes) vs +0.53 (heterozygotes) vs +0.79 (non-carriers)
- Evidence strengthModerate
Limitations
Participants were psychologically pre-screened, motivated trial volunteers and overwhelmingly white, so results may not generalise to routine clinical disclosure; self-reported outcomes; effects measured up to 12 months.
How this study scored 63/100
Published in a leading specialty 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 free to read, so that was left out: it earned 62 of the 98 points we could judge it on, which is 63 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (The Lancet Healthy Longevity) |
| Journal's citation record | 1 / 4 | The Lancet Healthy Longevity: journal h-index 78 (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 | 3 / 4 | 9,496 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 8 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 5.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Jason H. Karlawish: h-index 88 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41319675) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 62 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 62 of the 98 points we could judge it on is 63 out of 100. |
| Total | 63 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.lanhl.2025.100778
- PubMed: 41319675
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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