Home › Research › Brain scans and imaging
Orthogonal Contributions of Genetic, Clinical, and Social Determinants of Health Risk Burdens on Alzheimer’s Disease Pathophysiology
Okorie M, Jiang X, Tolosa-Tort P, Sharma RU, Clark AL, Yaffe K, Yokoyama JS, Andrews S et al.. medRxiv, 2026-07-15
Topic: Genetics and APOE
Results The total analytic sample included 2,276 participants (mean age: 65.3 ± 8.7; non-Hispanic White: 43.0%, non-Hispanic Black: 16.2%, and Latinx/Hispanic adults: 40.8%). APOE ε4 was strongly associated with worse Aβ/tau latent variable (β=0.31; p<0.001), with smaller but significant associations with neurodegeneration (β=0.085; p<0.001) and cognition (β=0.083; p<0.001). Higher AD-PRS was modestly associated with worse Aβ/tau (β=0.075; p<0.01) but was not associated with neurodegeneration or cognition. A higher clinical risk score was significantly associated with worse neurodegeneration (β=0.16; p<0.001) but not with Aβ/tau or cognition. Adverse SDoH was associated with worse neurodegeneration (β=0.071; p<0.05) and strongly associated with worse cognition (β=0.22; p<0.001), with no associations with Aβ/tau. Conclusion and Relevance Genetic risks were primarily associated with Aβ and tau pathology, clinical risks with neurodegeneration, and SDoH risks with cognition, suggesting that risk factors exert differential effects on AD pathophysiology. Findings Genetic and genomic risk burdens demonstrated the strongest associations with amyloid and tau pathology; clinical risk burden with neurodegeneration; and adverse social determinants of health with cognition.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Okorie, M., Jiang, X., Tolosa-Tort, P., Sharma, R. U., Clark, A. L., Yaffe, K., et al. (2026). Orthogonal Contributions of Genetic, Clinical, and Social Determinants of Health Risk Burdens on Alzheimer’s Disease Pathophysiology. medRxiv. https://doi.org/10.64898/2026.07.07.26357509
Vancouver
Okorie M, Jiang X, Tolosa-Tort P, Sharma RU, Clark AL, Yaffe K, et al. Orthogonal Contributions of Genetic, Clinical, and Social Determinants of Health Risk Burdens on Alzheimer’s Disease Pathophysiology. medRxiv. 2026. doi:10.64898/2026.07.07.26357509.
BibTeX
@article{okorie2026-b68cebbb,
author = {Okorie, M. and Jiang, X. and Tolosa-Tort, P. and Sharma, R. U. and Clark, A. L. and Yaffe, K. and Yokoyama, J. S. and Andrews, S. and others},
title = {{Orthogonal Contributions of Genetic, Clinical, and Social Determinants of Health Risk Burdens on Alzheimer’s Disease Pathophysiology}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.07.07.26357509},
url = {https://doi.org/10.64898/2026.07.07.26357509}
}
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.
Key findings
- Results The total analytic sample included 2,276 participants (mean age: 65.3 ± 8.7; non-Hispanic White: 43.0%, non-Hispanic Black: 16.2%, and Latinx/Hispanic adults: 40.8%).
- APOE ε4 was strongly associated with worse Aβ/tau latent variable (β=0.31; p<0.001), with smaller but significant associations with neurodegeneration (β=0.085; p<0.001) and cognition (β=0.083; p<0.001).
- Higher AD-PRS was modestly associated with worse Aβ/tau (β=0.075; p<0.01) but was not associated with neurodegeneration or cognition.
- A higher clinical risk score was significantly associated with worse neurodegeneration (β=0.16; p<0.001) but not with Aβ/tau or cognition.
- Adverse SDoH was associated with worse neurodegeneration (β=0.071; p<0.05) and strongly associated with worse cognition (β=0.22; p<0.001), with no associations with Aβ/tau.
New to this subject? Start with our plain-English guide: Brain scans & tests →
Study details
- Study designcohort study
- Participants2,276
- Effect size43.0%; 16.2%; 40.8%
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 48 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for randomized / blinded because the record does not state it. We have no data on 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 multicenter collaboration, so those were left out: it earned 30 of the 62 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 2,276 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 | — / 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 30 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 30 of the 62 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in Brain scans and imaging
Also tagged “genetics”
346 studies in the library carry the topic tag “genetics”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 346 tagged studies.