Multimorbidity, Cognition, and Alzheimer Disease Biomarkers: A Pathway Analysis
Xiaqing Jiang, Sid E. O’Bryant, Robert A. Rissman, Leigh A Johnson, Meredith N. Braskie, Kristine S. Yaffe. Alzheimer s & Dementia, 2025-12-01
Topic: Amyloid, tau and blood-test diagnosis
After adjusting for age, sex, race/ethnicity, education, APOE ε4, and physical activity, a greater multimorbidity burden (per 3 additional conditions) was associated with worse overall cognition (standardized β = -0.074, 95%CI -0.104 to -0.043) and biomarkers indicative of greater AD pathology, neurodegeneration, and SVD (Figure 1). The direct association between multimorbidity and cognition was attenuated (standardized β = 0.024, 95%CI -0.023 to 0.071) after accounting for the mediating pathways (Figure 2). SEM showed that the association between multimorbidity and worse cognition was primarily mediated by neurodegeneration (74%, standardized β = -0.072, 95%CI -0.109 to -0.035) and partially by AD pathology (22%, standardized β = -0.022, 95%CI -0.038 to -0.005), after multivariable adjustment. Among dementia-free individuals, greater multimorbidity burden was associated with biomarkers indicative of greater AD pathology, neurodegeneration, and cerebral SVD. Multimorbidity may contribute to cognition via both neurodegeneration and AD pathways.
Key findings
- After adjusting for age, sex, race/ethnicity, education, APOE ε4, and physical activity, a greater multimorbidity burden (per 3 additional conditions) was associated with worse overall cognition (standardized β = -0.074, 95%CI -0.104 to -0.043) and biomarkers indicative of greater AD pathology, neurodegeneration, and SVD (Figure 1).
- The direct association between multimorbidity and cognition was attenuated (standardized β = 0.024, 95%CI -0.023 to 0.071) after accounting for the mediating pathways (Figure 2).
- SEM showed that the association between multimorbidity and worse cognition was primarily mediated by neurodegeneration (74%, standardized β = -0.072, 95%CI -0.109 to -0.035) and partially by AD pathology (22%, standardized β = -0.022, 95%CI -0.038 to -0.005), after multivariable adjustment.
- Among dementia-free individuals, greater multimorbidity burden was associated with biomarkers indicative of greater AD pathology, neurodegeneration, and cerebral SVD.
- Multimorbidity may contribute to cognition via both neurodegeneration and AD pathways.
Why it matters
This pathway analysis found that a greater multimorbidity burden was associated with worse overall cognition and with biomarkers of greater Alzheimer disease pathology, neurodegeneration, and small vessel disease. The association between multimorbidity and worse cognition was primarily mediated by neurodegeneration and partially by Alzheimer disease pathology.
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Study details
- Evidence strengthModerate
How this study scored 37/100
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 | 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 | 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 | 4 / 4 | Last-listed author Kristine S. Yaffe: h-index 155 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41434402) |
| Free to read | 2 / 2 | Free to read |
| Total | 37 / 100 | — |
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Read the original
- DOI: 10.1002/alz70862_110144
- PubMed: 41434402
- 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
Jiang, X., O’Bryant, S. E., Rissman, R. A., Johnson, L. A., Braskie, M. N., & Yaffe, K. S. (2025). Multimorbidity, Cognition, and Alzheimer Disease Biomarkers: A Pathway Analysis. Alzheimer s & Dementia. https://doi.org/10.1002/alz70862_110144
Vancouver
Jiang X, O’Bryant SE, Rissman RA, Johnson LA, Braskie MN, Yaffe KS. Multimorbidity, Cognition, and Alzheimer Disease Biomarkers: A Pathway Analysis. Alzheimer s & Dementia. 2025. doi:10.1002/alz70862_110144. PMID: 41434402.
BibTeX
@article{jiang2025-41434402,
author = {Jiang, Xiaqing and O’Bryant, Sid E. and Rissman, Robert A. and Johnson, Leigh A and Braskie, Meredith N. and Yaffe, Kristine S.},
title = {{Multimorbidity, Cognition, and Alzheimer Disease Biomarkers: A Pathway Analysis}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70862_110144},
pmid = {41434402},
url = {https://doi.org/10.1002/alz70862_110144}
}
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