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Existing Pittsburgh Compound-B positron emission tomography thresholds are too high: statistical and pathological evaluation
Villeneuve S, Rabinovici GD, Cohn-Sheehy BI, Madison C, Ayakta N, Ghosh PM, La Joie R, Arthur-Bentil SK et al.. Brain : a journal of neurology, 2015-05-06
Topic: Brain proteins, microglia and lab models
When compared to post-mortem amyloid burden, low proposed thresholds were more sensitive than high thresholds (sensitivities: distribution volume ratiolow 81.0%, standard uptake value ratiolow 83.3%; distribution volume ratiohigh 61.9%, standard uptake value ratiohigh 62.5%) for CERAD moderate-to-frequent neuritic plaques, with similar specificity (distribution volume ratiolow 95.8%; standard uptake value ratiolow, distribution volume ratiohigh and standard uptake value ratiohigh 100.0%). In summary, we found that frequently applied thresholds for Pittsburgh compound-B positivity (typically at or above distribution volume ratiohigh and standard uptake value ratiohigh) are overly stringent in defining amyloid positivity.
Key findings
- When compared to post-mortem amyloid burden, low proposed thresholds were more sensitive than high thresholds (sensitivities: distribution volume ratiolow 81.0%, standard uptake value ratiolow 83.3%; distribution volume ratiohigh 61.9%, standard uptake value ratiohigh 62.5%) for CERAD moderate-to-frequent neuritic plaques, with similar specificity (distribution volume ratiolow 95.8%; standard uptake value ratiolow, distribution volume ratiohigh and standard uptake value ratiohigh 100.0%).
- In summary, we found that frequently applied thresholds for Pittsburgh compound-B positivity (typically at or above distribution volume ratiohigh and standard uptake value ratiohigh) are overly stringent in defining amyloid positivity.
Why it matters
When PiB amyloid PET scans were checked against plaques counted in the brain after death, the commonly used "high" cut-offs caught only about 62% of brains with moderate-to-frequent plaques, while lower cut-offs caught 81–83%. The lower cut-offs gave up almost no specificity (95.8–100%), so the authors conclude that frequently applied PiB thresholds are "overly stringent in defining amyloid positivity." The record gives no threshold values, sample sizes or confidence intervals, applies only to the PiB tracer, and does not test any treatment.
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Study details
- Participants50
- Effect size81.0%; 83.3%; 61.9%
- Evidence strengthLow
How this study scored 63/100
Published in a leading specialty journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 50 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 6 / 7 | Cited 411 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 31.6 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 5 / 6 | Cited 23.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 43 other studies in this library |
| Still being cited | 3 / 4 | Cited 99 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author William J. Jagust: h-index 152 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, Berkeley: institution h-index 2,012 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25953778) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 63 / 100 | — |
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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. 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
Villeneuve, S., Rabinovici, G. D., Cohn-Sheehy, B. I., Madison, C., Ayakta, N., Ghosh, P. M., et al. (2015). Existing Pittsburgh Compound-B positron emission tomography thresholds are too high: statistical and pathological evaluation. Brain : a journal of neurology. https://doi.org/10.1093/brain/awv112
Vancouver
Villeneuve S, Rabinovici GD, Cohn-Sheehy BI, Madison C, Ayakta N, Ghosh PM, et al. Existing Pittsburgh Compound-B positron emission tomography thresholds are too high: statistical and pathological evaluation. Brain : a journal of neurology. 2015. doi:10.1093/brain/awv112. PMID: 25953778.
BibTeX
@article{villeneuve2015-25953778,
author = {Villeneuve, S. and Rabinovici, G. D. and Cohn-Sheehy, B. I. and Madison, C. and Ayakta, N. and Ghosh, P. M. and La Joie, R. and Arthur-Bentil, S. K. and others},
title = {{Existing Pittsburgh Compound-B positron emission tomography thresholds are too high: statistical and pathological evaluation}},
journal = {Brain : a journal of neurology},
year = {2015},
doi = {10.1093/brain/awv112},
pmid = {25953778},
url = {https://doi.org/10.1093/brain/awv112}
}
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