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Defining the Lowest Threshold for Amyloid-PET to Predict Future Cognitive Decline and Amyloid Accumulation
Farrell ME, Jiang S, Schultz AP, Properzi MJ, Price JC, Becker JA, Jacobs HIL, Hanseeuw BJ et al.. Neurology, 2020-11-16
Topic: Amyloid, tau and blood-test diagnosis
Introduction As clinical trials move toward earlier intervention, we sought to redefine the β-amyloid (Aβ)-PET threshold based on the lowest point in a baseline distribution that robustly predicts future Aβ accumulation and cognitive decline in 3 independent samples of clinically normal individuals. Methods Sequential Aβ cutoffs were tested to identify the lowest cutoff associated with future change in cognition (Preclinical Alzheimer Cognitive Composite [PACC]) and Aβ-PET in clinically normal participants from the Harvard Aging Brain Study (n = 342), Australian Imaging, Biomarker and Lifestyle study of aging (n = 157), and Alzheimer's Disease Neuroimaging Initiative (n = 356). Results Within samples, cutoffs derived from future Aβ-PET accumulation and PACC decline converged on the same inflection point, beyond which trajectories diverged from normal. Across samples, optimal cutoffs fell within a short range (Centiloid 15-18.5). Discussion These optimized thresholds can help to inform future research and clinical trials targeting early Aβ. Threshold convergence raises the possibility of contemporaneous early changes in Aβ and cognition. Classification of evidence This study provides Class II evidence that among clinically normal individuals a specific Aβ-PET threshold is predictive of cognitive decline.
Key findings
- Methods Sequential Aβ cutoffs were tested to identify the lowest cutoff associated with future change in cognition (Preclinical Alzheimer Cognitive Composite [PACC]) and Aβ-PET in clinically normal participants from the Harvard Aging Brain Study (n = 342), Australian Imaging, Biomarker and Lifestyle study of aging (n = 157), and Alzheimer's Disease Neuroimaging Initiative (n = 356).
- Results Within samples, cutoffs derived from future Aβ-PET accumulation and PACC decline converged on the same inflection point, beyond which trajectories diverged from normal.
Why it matters
In three independent samples of clinically normal individuals, the lowest amyloid-PET thresholds that predicted future amyloid accumulation and cognitive decline converged within a short range. This is about defining an imaging threshold for early research and trials, not about treating, curing or preventing Alzheimer disease.
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Study details
- Participants342
- Evidence strengthLow
Limitations
All three cohorts studied only cognitively normal older adults, so this lower threshold's relevance to people who already have symptoms isn't addressed here.
How this study scored 59/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 342 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 | 5 / 7 | Cited 128 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.3 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 7.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 3 / 4 | Cited 83 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Rachel F. Buckley: h-index 52 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33199430) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 59 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0000000000011214
- PubMed: 33199430
- Original source →
- Free full text: PubMed Central →
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
Farrell, M. E., Jiang, S., Schultz, A. P., Properzi, M. J., Price, J. C., Becker, J. A., et al. (2021). Defining the Lowest Threshold for Amyloid-PET to Predict Future Cognitive Decline and Amyloid Accumulation. Neurology. https://doi.org/10.1212/wnl.0000000000011214
Vancouver
Farrell ME, Jiang S, Schultz AP, Properzi MJ, Price JC, Becker JA, et al. Defining the Lowest Threshold for Amyloid-PET to Predict Future Cognitive Decline and Amyloid Accumulation. Neurology. 2021. doi:10.1212/wnl.0000000000011214. PMID: 33199430.
BibTeX
@article{farrell2021-33199430,
author = {Farrell, M. E. and Jiang, S. and Schultz, A. P. and Properzi, M. J. and Price, J. C. and Becker, J. A. and Jacobs, H. I. L. and Hanseeuw, B. J. and others},
title = {{Defining the Lowest Threshold for Amyloid-PET to Predict Future Cognitive Decline and Amyloid Accumulation}},
journal = {Neurology},
year = {2021},
doi = {10.1212/wnl.0000000000011214},
pmid = {33199430},
url = {https://doi.org/10.1212/wnl.0000000000011214}
}
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