Topic: Amyloid, tau and blood-test diagnosis
We evaluated known AD-associated loci (Bellenguez et al. 2022) and 27 loci reached nominal significance (p < 0.05) in at least one cognitive domain. Of these, 8 were nominally significant in exactly one domain, 11 in two domains, and 7 (including APOE4, APOE2, ABCA7, USP6NL, WNT3, CD2AP, and EPDR1) in all three domains. Notably, APOE4 displayed the strongest overall effects, with the stronger effect size on memory (BETA_mem = -0.28, p = 1.10×10^-58) and comparatively weaker yet still significant effects on language (BETA_lan = -0.14, p = 2.59×10^-19) and executive function (BETA_exf = -0.12, p = 2.30×10^-17). These results underscore both the broad influence of certain variants across multiple cognitive measures and variation in effect magnitude by domain. These findings enhance our understanding of the biological mechanisms that contribute to domain-specific cognitive decline in AD, underscoring the distinct processes driving deficits in memory, language, and executive function. Such insights pave the way for more precise, syndrome-focused interventions, ultimately guiding a precision medicine approach tailored to the heterogeneous clinical manifestations of AD.
Key findings
- We evaluated known AD-associated loci (Bellenguez et al. 2022) and 27 loci reached nominal significance (p < 0.05) in at least one cognitive domain.
- Of these, 8 were nominally significant in exactly one domain, 11 in two domains, and 7 (including APOE4, APOE2, ABCA7, USP6NL, WNT3, CD2AP, and EPDR1) in all three domains.
- Notably, APOE4 displayed the strongest overall effects, with the stronger effect size on memory (BETA_mem = -0.28, p = 1.10×10^-58) and comparatively weaker yet still significant effects on language (BETA_lan = -0.14, p = 2.59×10^-19) and executive function (BETA_exf = -0.12, p = 2.30×10^-17).
- These results underscore both the broad influence of certain variants across multiple cognitive measures and variation in effect magnitude by domain.
- These findings enhance our understanding of the biological mechanisms that contribute to domain-specific cognitive decline in AD, underscoring the distinct processes driving deficits in memory, language, and executive function.
Why it matters
This study found that some known Alzheimer risk genes affect memory, language, and executive function differently, with APOE4 showing the strongest effect on memory. It suggests that understanding these domain-specific genetic effects could guide more precise, symptom-focused interventions, though no intervention was tested.
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Study details
- Evidence strengthLow
How this study scored 30/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 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 3 year(s) since 2025 |
| 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 | 1 / 4 | Last-listed author Farid Rajabli: h-index 17 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Miami: institution h-index 998 (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 41442684) |
| Free to read | 2 / 2 | Free to read |
| Total | 30 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/alz70855_105459
- PubMed: 41442684
- Original source →
- Free full text: Alzheimer s & Dementia →
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. Check the citation against the original before you use it.
APA 7th
Scott, K. M., Emekci, A., Aguiar‐Pulido, V., & Rajabli, F. (2025). Genome‐Wide Analysis of Memory, Language, and Executive Function Reveals Domain‐Specific Genetic Architecture in Alzheimer Disease. Alzheimer s & Dementia. https://doi.org/10.1002/alz70855_105459
Vancouver
Scott KM, Emekci A, Aguiar‐Pulido V, Rajabli F. Genome‐Wide Analysis of Memory, Language, and Executive Function Reveals Domain‐Specific Genetic Architecture in Alzheimer Disease. Alzheimer s & Dementia. 2025. doi:10.1002/alz70855_105459. PMID: 41442684.
BibTeX
@article{scott2025-41442684,
author = {Scott, Kyle M and Emekci, Azra and Aguiar‐Pulido, Vanessa and Rajabli, Farid},
title = {{Genome‐Wide Analysis of Memory, Language, and Executive Function Reveals Domain‐Specific Genetic Architecture in Alzheimer Disease}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70855_105459},
pmid = {41442684},
url = {https://doi.org/10.1002/alz70855_105459}
}