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Amyloid pathology and modifiable risk factors in cognitive decline among cognitively unimpaired older adults
Ying‐Hsin Hsu, Chih‐Kuang Liang, Chou, Jaysón Davidson, Y H Wang, Mike A. Nalls, Luigi Ferrucci, Mark Cookson et al.. The Journal of Prevention of Alzheimer s Disease, 2026-05-01
Topic: Amyloid, tau and blood-test diagnosis
Significant interactions between amyloid status and modifiable risk factors were observed for diabetes (adjusted β = -0.206, p = 0.032), high cholesterol (adjusted β = -0.155, p < 0.001), and physical inactivity (adjusted β = -0.161, p = 0.046), indicating combined effects rather than additive effects on cognitive decline among Aβ+ individuals. In the A4 study (Aβ+), low education, diabetes, high cholesterol, and physical inactivity were independently associated with accelerated cognitive decline, whereas obesity was linked to slower decline. In contrast, in the LEARN study (Aβ-), these associations were not statistically significant. In conclusion, the significant interactions with amyloid status were observed for diabetes, high cholesterol, and physical inactivity, indicating that these risk factors were associated with faster cognitive decline specifically in Aβ+ individuals. The results suggest that consideration of amyloid status may be important when evaluating the potential role of metabolic and lifestyle risk factors in preclinical cognitive decline. In Aβ+ individuals, obesity was associated with slower cognitive decline, while low education was linked to lower baseline cognition or a reduced symptom threshold, without a significant interaction with amyloid status. Future studies should incorporate amyloid status and longitudinal biomarkers to assess whether modifying these factors can slow preclinical cognitive decline.
Key findings
- Significant interactions between amyloid status and modifiable risk factors were observed for diabetes (adjusted β = -0.206, p = 0.032), high cholesterol (adjusted β = -0.155, p < 0.001), and physical inactivity (adjusted β = -0.161, p = 0.046), indicating combined effects rather than additive effects on cognitive decline among Aβ+ individuals.
- In the A4 study (Aβ+), low education, diabetes, high cholesterol, and physical inactivity were independently associated with accelerated cognitive decline, whereas obesity was linked to slower decline.
- In contrast, in the LEARN study (Aβ-), these associations were not statistically significant.
- In conclusion, the significant interactions with amyloid status were observed for diabetes, high cholesterol, and physical inactivity, indicating that these risk factors were associated with faster cognitive decline specifically in Aβ+ individuals.
- The results suggest that consideration of amyloid status may be important when evaluating the potential role of metabolic and lifestyle risk factors in preclinical cognitive decline.
Why it matters
In this cohort study, diabetes, high cholesterol, and physical inactivity were associated with faster cognitive decline specifically in amyloid-positive individuals, suggesting combined rather than additive effects. In amyloid-negative participants these associations were not statistically significant, and the authors say future studies should assess whether modifying these factors changes outcomes.
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Study details
- Study designcohort study
- Participants1,707
- Evidence strengthModerate
How this study scored 53/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of Prevention of Alzheimer s Disease) |
| Journal's citation record | 0 / 4 | The Journal of Prevention of Alzheimer s Disease: journal h-index 63 (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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,707 participants |
| 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 (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.7× 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 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Hirotaka Iwaki: h-index 32 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42060990) |
| Free to read | 2 / 2 | Free to read |
| Total | 53 / 100 | — |
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Read the original
- DOI: 10.1016/j.tjpad.2026.100574
- PubMed: 42060990
- Original source →
- Free full text: The Journal of Prevention of Alzheimer s Disease →
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. 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
Hsu, Y., Liang, C., Chou, Davidson, J., Wang, Y. H., Nalls, M. A., et al. (2026). Amyloid pathology and modifiable risk factors in cognitive decline among cognitively unimpaired older adults. The Journal of Prevention of Alzheimer s Disease. https://doi.org/10.1016/j.tjpad.2026.100574
Vancouver
Hsu Y, Liang C, Chou, Davidson J, Wang YH, Nalls MA, et al. Amyloid pathology and modifiable risk factors in cognitive decline among cognitively unimpaired older adults. The Journal of Prevention of Alzheimer s Disease. 2026. doi:10.1016/j.tjpad.2026.100574. PMID: 42060990.
BibTeX
@article{hsu2026-42060990,
author = {Hsu, Ying‐Hsin and Liang, Chih‐Kuang and Chou and Davidson, Jaysón and Wang, Y H and Nalls, Mike A. and Ferrucci, Luigi and Cookson, Mark and others},
title = {{Amyloid pathology and modifiable risk factors in cognitive decline among cognitively unimpaired older adults}},
journal = {The Journal of Prevention of Alzheimer s Disease},
year = {2026},
doi = {10.1016/j.tjpad.2026.100574},
pmid = {42060990},
url = {https://doi.org/10.1016/j.tjpad.2026.100574}
}
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