Journal Article

DZNE-2026-01027

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Amyloid PET Quantitation and Centiloid Thresholds in the Diagnosis of Alzheimer Disease: An Individual Participant Data Meta-Analysis.

Blazhenets, G. ; Soleimani-Meigooni, D. N. ; Chiotis, K. ; Allen, I. E. ; Rabinovici, G. D. ; La Joie, R. ; Group, M. S. (Collaboration Author) ; Apostolova, L. G. ; Asken, B. M. ; Bejanin, A. ; Benzinger, T. L. S. ; Betthauser, T. J. ; Bluma, M. ; Bombois, S. ; Bourgeat, P. ; Bouteloup, V. ; Braskie, M. N. ; Brendel, M.DZNE* ; Brickman, A. M. ; Bryant, N. ; Bullich, S. ; Carrillo, M. C. ; Casaletto, K. ; Cash, D. M. ; Chang, C.-C. ; Chang, H.-I. ; Chao, Y. ; Chêne, G. ; Chételat, G. ; Coath, W. ; Collij, L. E. ; Colmant, L. ; Corrada, M. M. ; Craft, S. ; Dickerson, B. C. ; Dubois, B. ; Dufouil, C. ; Fajardo, A. ; Farrar, G. ; Fortea, J. ; Frings, L. ; Frisoni, G. B. ; Gardner, R. C. ; Garibotto, V. ; Gnoerich, J.Extern* ; Gordon, B. A. ; Gu, Y. ; Guan, Y. ; Guo, T. ; Hanseeuw, B. J. ; Hansson, O. ; Harrison, T. M. ; Huang, Q. ; Huang, S.-H. ; Iaccarino, L. ; Ishii, K. ; Ishi, K. ; Jagust, W. J. ; Johnson, S. C. ; Kato, T. ; Katsumi, Y. ; Kaye, J. ; Koeppe, R. A. ; Kolinger, G. D. ; Kramer, J. H. ; Landau, S. M. ; Landeau, B. ; Lao, P. J. ; Lee, S. ; Lleó, A. ; Lopresti, B. J. ; Lowe, V. J. ; Luchsinger, J. A. ; Malpetti, M. ; Mao, X. ; March, A. ; Masters, C. L. ; Meyer, P. T. ; Mezenge, F. ; Mormino, E. C. ; Franquesa-Mullerat, M. ; Nakamura, A. ; Nordberg, A. ; O'Brien, J. T. ; O'Bryant, S. E. ; Pappas, I. ; Peretti, D. E. ; Quenon, L. ; Rowe, C. C. ; Rowe, J. B. ; Rudolph, M. D. ; Salvadó, G. ; Schott, J. M. ; Schwartz, D. L. ; Schwarz, C. G. ; Seo, S. W. ; Shekari, M. ; Silbert, L. C. ; Smith, R. ; Snyder, H. M. ; Sokolowski, A. ; Sperling, R. A. ; Sun, P. ; Taggett, J. Z. ; Toga, A. W. ; Touroutoglou, A. ; Vaillancourt, D. E. ; van de Giessen, E. ; Vijverberg, J. ; Vemuri, P. ; Villain, N. ; Villemagne, V. L. ; Villeneuve, S. ; Wang, W.-E. ; Weiner, M. ; Woodworth, D. ; Xiao, C. ; Xie, F. ; Yoon, Y. ; Young, C. B. ; Yun, M. ; A, A. (Collaboration Author)

2026
American Medical Association Chicago, Ill.

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Please use a persistent id in citations: doi:10.1001/jama.2026.13116

Abstract: Amyloid positron emission tomography (PET) is increasingly used in research and clinical settings to determine the etiology of cognitive decline and eligibility for amyloid-targeting therapies. To assist with amyloid PET evaluation and to guide clinical decision-making, images can be quantified in a standardized unit called Centiloid, the interpretation of which can vary according to the method and threshold used.To collect Centiloid values from available studies and determine robust positivity cutoffs using data-driven methods and correspondence with visual reads.PubMed search (October 2024) identified studies with Centiloid values. Corresponding authors were invited to share individual participant data. Additional data were obtained through access-controlled repositories and conference outreach (July 2024-July 2025).Studies were included if they provided Centiloids, radiotracer, age, and sex.Each study was analyzed using a unified statistical pipeline; study estimates were pooled using random-effects meta-analysis.Gaussian mixture models (GMMs) were fitted to Centiloid values for each study. In studies with a bimodal distribution (per integrated completed likelihood), single cutoffs for positivity were set as mean plus 2 SDs of the lower gaussian component. Using GMMs, a double-cutoff approach defined a lower certainty range using a 90% posterior probability cutoff for assignment to the low (amyloid-negative) vs high (amyloid-positive) component. An alternative Centiloid cutoff was derived from maximizing the correspondence (Cohen κ) with the binary visual reads when available.This meta-analysis included cross-sectional amyloid PET scans acquired with 5 radiotracers from 49 227 participants across 53 studies from 15 countries (mean age, 71 years; 54% female, 62% cognitively impaired). The data-driven GMM approach identified a bimodal distribution in 51 studies (n = 48 786), resulting in a single cutoff for positivity of 18 Centiloids (95% CI,16-19; I2 = 97%). The double-cutoff approach revealed high confidence for interpreting scans as negative when Centiloid values were lower than 11 (95% CI, 9-13; I2 = 95%) and interpreting scans as positive if Centiloid values were higher than 26 (95% CI, 24-28; I2 = 95%). In analyses of correspondence with binary (positive or negative) visual reads of amyloid PET scans (n = 35 045; 36 studies), Centiloids were highly predictive of visual positivity (Cohen κ, 0.86; 95% CI, 0.83-0.89; I2 = 96%) with a cutoff of 27 Centiloids (95% CI, 24-30; I2 = 80%).In this individual participant data meta-analysis, positivity cutoffs converged around 18 Centiloids (data-driven) and 27 Centiloids (visual reads). Findings from a double-cutoff analysis suggest that scans in the 11 to 26 Centiloid range should be interpreted with caution depending on the context of use.

Keyword(s): Humans (MeSH) ; Positron-Emission Tomography: methods (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Amyloid (MeSH) ; Female (MeSH) ; Radiopharmaceuticals (MeSH) ; Male (MeSH) ; Amyloid ; Radiopharmaceuticals

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Contributing Institute(s):

1. Molecular Neurodegeneration (AG Haass)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 90 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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