Home › Research › Biomarkers
Amyloid and Tau Prediction of Cognitive and Functional Decline in Unimpaired Older Individuals: Longitudinal Data from the A4 and LEARN Studies
Sperling RA, Donohue MC, Rissman RA, Johnson KA, Rentz DM, Grill JD, Heidebrink JL, Jenkins C et al.. The journal of prevention of Alzheimer's disease, 2024-01-01
Topic: Amyloid, tau and blood-test diagnosis
Background Converging evidence suggests that markers of Alzheimer's disease (AD) pathology in cognitively unimpaired older individuals are associated with high risk of cognitive decline and progression to functional impairment. Models were evaluated to explore the impact of baseline tertiles of amyloid PET and tertiles of plasma P-tau217 on cognitive and functional outcomes in the A4 Study compared to LEARN. Results Higher baseline amyloid PET CL and P-tau217 levels were associated with faster rates of PACC decline, and increased likelihood of progression to functional impairment (CDR 0.5 or higher on two consecutive measurements), both across LEARN Aβ- and A4 Aβ+ (solanezumab and placebo arms). Conclusions In a large cohort of cognitively unimpaired individuals enrolled in a Phase 3 clinical trial and companion observational study, these findings confirm that higher baseline levels of amyloid and tau markers are associated with increased rates of cognitive decline and progression to functional impairment. Interestingly, plasma P-tau217 was the best predictor of decline in the overall sample, superior to baseline amyloid PET. Neocortical tau was the strongest predictor of cognitive decline in the subgroup with tau PET, suggesting that tau deposition is most closely linked to clinical decline. These findings indicate that biomarkers of AD pathology are useful to predict decline in an older asymptomatic population and may prove valuable in the selection of individuals for disease-modifying treatments.
Key findings
- Background Converging evidence suggests that markers of Alzheimer's disease (AD) pathology in cognitively unimpaired older individuals are associated with high risk of cognitive decline and progression to functional impairment.
- Models were evaluated to explore the impact of baseline tertiles of amyloid PET and tertiles of plasma P-tau217 on cognitive and functional outcomes in the A4 Study compared to LEARN.
- Results Higher baseline amyloid PET CL and P-tau217 levels were associated with faster rates of PACC decline, and increased likelihood of progression to functional impairment (CDR 0.5 or higher on two consecutive measurements), both across LEARN Aβ- and A4 Aβ+ (solanezumab and placebo arms).
- Conclusions In a large cohort of cognitively unimpaired individuals enrolled in a Phase 3 clinical trial and companion observational study, these findings confirm that higher baseline levels of amyloid and tau markers are associated with increased rates of cognitive decline and progression to functional impairment.
- Interestingly, plasma P-tau217 was the best predictor of decline in the overall sample, superior to baseline amyloid PET.
Why it matters
In cognitively unimpaired older adults, higher baseline amyloid PET and plasma P-tau217 were linked to faster cognitive decline and progression to functional impairment, with P-tau217 the best predictor overall. These markers may help predict decline, but the study does not show that any treatment, cure, or prevention works.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designlongitudinal study
- Participants583
- Evidence strengthHigh
How this study scored 74/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for effect reported 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 | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 583 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 | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 5 / 7 | Cited 115 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 28.8 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 5 / 6 | Cited 31.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 20 other studies in this library |
| Still being cited | 3 / 4 | Cited 115 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Paul S. S Aisen: h-index 87 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39044488) |
| Free to read | 2 / 2 | Free to read |
| Total | 74 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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
Sperling, R. A., Donohue, M. C., Rissman, R. A., Johnson, K. A., Rentz, D. M., Grill, J. D., et al. (2024). Amyloid and Tau Prediction of Cognitive and Functional Decline in Unimpaired Older Individuals: Longitudinal Data from the A4 and LEARN Studies. The journal of prevention of Alzheimer's disease. https://doi.org/10.14283/jpad.2024.122
Vancouver
Sperling RA, Donohue MC, Rissman RA, Johnson KA, Rentz DM, Grill JD, et al. Amyloid and Tau Prediction of Cognitive and Functional Decline in Unimpaired Older Individuals: Longitudinal Data from the A4 and LEARN Studies. The journal of prevention of Alzheimer's disease. 2024. doi:10.14283/jpad.2024.122. PMID: 39044488.
BibTeX
@article{sperling2024-39044488,
author = {Sperling, R. A. and Donohue, M. C. and Rissman, R. A. and Johnson, K. A. and Rentz, D. M. and Grill, J. D. and Heidebrink, J. L. and Jenkins, C. and others},
title = {{Amyloid and Tau Prediction of Cognitive and Functional Decline in Unimpaired Older Individuals: Longitudinal Data from the A4 and LEARN Studies}},
journal = {The journal of prevention of Alzheimer's disease},
year = {2024},
doi = {10.14283/jpad.2024.122},
pmid = {39044488},
url = {https://doi.org/10.14283/jpad.2024.122}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 25.
Later studies that cite this one
20 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.