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Polygenicity and APOE ε4 shape response to intervention in mild cognitive impairment
Jiyun Hwang, So Young Moon, Harim Lee, Jaejin Lee, Yoo Kyoung Park, Jee Hyang Jeong, Chang Hyung Hong, Jiwoo Jung et al.. Alzheimer's research & therapy, 2025-12-12
Topic: Genetics and APOE
Both intervention and control groups showed cognitive improvement over 24 weeks, with greater gains in the intervention arm. Relative intervention efficacy (RIE) increased with higher genetic risk, being most pronounced among APOE ε4 carriers and individuals with high PRS. When both factors were considered jointly, APOE ε4 carriers with high PRS exhibited the largest RIE (β = 7.54, SE = 2.59, p = 0.005), driven by markedly greater improvement in the intervention group. The secondary outcomes did not show as consistent results as RBANS total index. These findings suggest that MCI individuals who are APOE ε4 carriers with high PRS may benefit most from multidomain interventions. These results support the complementary use of PRS and APOE status for identifying high-risk subgroups most likely to benefit from multidomain interventions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05023057. Registered on 26 August 2021.
Key findings
- Both intervention and control groups showed cognitive improvement over 24 weeks, with greater gains in the intervention arm.
- Relative intervention efficacy (RIE) increased with higher genetic risk, being most pronounced among APOE ε4 carriers and individuals with high PRS.
- When both factors were considered jointly, APOE ε4 carriers with high PRS exhibited the largest RIE (β = 7.54, SE = 2.59, p = 0.005), driven by markedly greater improvement in the intervention group.
- The secondary outcomes did not show as consistent results as RBANS total index.
- These findings suggest that MCI individuals who are APOE ε4 carriers with high PRS may benefit most from multidomain interventions.
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Study details
- Evidence strengthLow
How this study scored 69/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for sample size and effect reported because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and free to read, so those were left out: it earned 41 of the 59 points we could judge it on, which is 69 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's research & therapy) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 1 / 5 | Rated “low” 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| 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 | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41388319) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 41 / 59 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 41 of the 59 points we could judge it on is 69 out of 100. |
| Total | 69 / 100 | — |
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
Hwang, J., Moon, S. Y., Lee, H., Lee, J., Park, Y. K., Jeong, J. H., et al. (2025). Polygenicity and APOE ε4 shape response to intervention in mild cognitive impairment. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-025-01907-3
Vancouver
Hwang J, Moon SY, Lee H, Lee J, Park YK, Jeong JH, et al. Polygenicity and APOE ε4 shape response to intervention in mild cognitive impairment. Alzheimer's research & therapy. 2025. doi:10.1186/s13195-025-01907-3. PMID: 41388319.
BibTeX
@article{hwang2025-41388319,
author = {Hwang, Jiyun and Moon, So Young and Lee, Harim and Lee, Jaejin and Park, Yoo Kyoung and Jeong, Jee Hyang and Hong, Chang Hyung and Jung, Jiwoo and others},
title = {{Polygenicity and APOE ε4 shape response to intervention in mild cognitive impairment}},
journal = {Alzheimer's research \& therapy},
year = {2025},
doi = {10.1186/s13195-025-01907-3},
pmid = {41388319},
url = {https://doi.org/10.1186/s13195-025-01907-3}
}
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