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A data-driven regional amyloid PET score predicts cognitive decline beyond Centiloid
Hirose, T.; Akamatsu, W.; Kato, T.. medRxiv (preprint), 2026-08-31
Topic: Amyloid, tau and blood-test diagnosis
BackgroundThe Centiloid (CL) scale standardizes global amyloid PET quantification and is widely used to define amyloid positivity. As a global summary measure, however, CL may not fully reflect the regional distribution of amyloid deposition, which can carry additional prognostic information about the rate of cognitive decline. ObjectiveTo develop and externally validate a fixed, regional amyloid PET composite score that complements CL for predicting cognitive decline in Alzheimers disease. MethodsThe Regional Amyloid PET Score (RAPS) was derived from 82 FreeSurfer regions using machine learning with bootstrap stability selection to predict the rate of change in CDR-Sum of Boxes (CDR-SB) in 433 amyloid-positive ADNI [18F]florbetapir participants. The fixed nine-region weights were applied without retraining in a cross-tracer ADNI [18F]florbetaben subset (N = 71; largely overlapping the discovery participants) and two external validation cohorts, NACC SCAN (N = 1531; four tracers) and OASIS-3 (N = 428). ResultsRAPS comprised nine regions. In ADNI, RAPS correlated more strongly with CDR-SB slope than CL and showed higher discrimination of rapid decliners (AUC 0.813 vs 0.713). Performance was directionally consistent across validation cohorts; in NACC SCAN, RAPS and CL independently predicted clinical progression. Cross-cohort meta-analysis of the three independent cohorts supported incremental discrimination beyond CL (pooled {Delta}AUC +0.066; I2 = 0%). ConclusionsRAPS, a fixed regional amyloid PET-derived score, may complement CL for prognostic stratification in Alzheimers disease research.
Key findings
- The fixed nine-region weights were applied without retraining in a cross-tracer ADNI [18F]florbetaben subset (N = 71; largely overlapping the discovery participants) and two external validation cohorts, NACC SCAN (N = 1531; four tracers) and OASIS-3 (N = 428).
- In ADNI, RAPS correlated more strongly with CDR-SB slope than CL and showed higher discrimination of rapid decliners (AUC 0.813 vs 0.713).
- Performance was directionally consistent across validation cohorts; in NACC SCAN, RAPS and CL independently predicted clinical progression.
- Cross-cohort meta-analysis of the three independent cohorts supported incremental discrimination beyond CL (pooled {Delta}AUC +0.066; I2 = 0%).
- ConclusionsRAPS, a fixed regional amyloid PET-derived score, may complement CL for prognostic stratification in Alzheimers disease research.
Why it matters
This study developed a nine-region amyloid PET score that predicted cognitive decline more strongly than the Centiloid scale in ADNI and performed consistently in external validation cohorts. It is a prognostic imaging tool, not a treatment or cure.
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Study details
- Study designmeta-analysis
- Participants71
- Effect sizeAUC 0.813
- Evidence strengthHigh
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 40 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. We have no data on impact for its field and year, so that was left out: it earned 38 of the 94 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv (preprint)) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” 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 | 1 / 4 | 71 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| 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 | 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 | 0 / 4 | Last-listed author Alzheimer’s Disease Neuroimaging Initiative: h-index 3 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Juntendo University: institution h-index 530 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 38 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 38 of the 94 points we could judge it on is 40 out of 100. |
| Total | 40 / 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
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
Hirose, T., Akamatsu, W., & Kato, T. (2026). A data-driven regional amyloid PET score predicts cognitive decline beyond Centiloid. medRxiv (preprint). https://doi.org/10.64898/2026.08.26.26360248
Vancouver
Hirose T, Akamatsu W, Kato T. A data-driven regional amyloid PET score predicts cognitive decline beyond Centiloid. medRxiv (preprint). 2026. doi:10.64898/2026.08.26.26360248.
BibTeX
@article{hirose2026-b90b0bb3,
author = {Hirose, T. and Akamatsu, W. and Kato, T.},
title = {{A data-driven regional amyloid PET score predicts cognitive decline beyond Centiloid}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.08.26.26360248},
url = {https://doi.org/10.64898/2026.08.26.26360248}
}
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