{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T22:28:36Z","timestamp":1793744916604,"version":"4.6.1"},"reference-count":47,"publisher":"American Medical Association (AMA)","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"\n Importance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To collect Centiloid values from available studies and determine robust positivity cutoffs using data-driven methods and correspondence with visual reads.<\/jats:p>\n <\/jats:sec>\n \n Data Sources<\/jats:title>\n 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).<\/jats:p>\n <\/jats:sec>\n \n Study Selection<\/jats:title>\n Studies were included if they provided Centiloids, radiotracer, age, and sex.<\/jats:p>\n <\/jats:sec>\n \n Data Extraction and Synthesis<\/jats:title>\n Each study was analyzed using a unified statistical pipeline; study estimates were pooled using random-effects meta-analysis.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n 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 \u03ba) with the binary visual reads when available.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n This meta-analysis included cross-sectional amyloid PET scans acquired with 5 radiotracers from 49\u202f227 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\u2009=\u200948\u202f786), resulting in a single cutoff for positivity of 18 Centiloids (95% CI,16-19;\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200997%). The double-cutoff approach revealed high confidence for interpreting scans as negative when Centiloid values were lower than 11 (95% CI, 9-13;\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200995%) and interpreting scans as positive if Centiloid values were higher than 26 (95% CI, 24-28;\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200995%). In analyses of correspondence with binary (positive or negative) visual reads of amyloid PET scans (n\u2009=\u200935\u202f045; 36 studies), Centiloids were highly predictive of visual positivity (Cohen \u03ba, 0.86; 95% CI, 0.83-0.89;\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200996%) with a cutoff of 27 Centiloids (95% CI, 24-30;\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200980%).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jama.2026.13116","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:30:17Z","timestamp":1783960217000},"page":"1135","source":"Crossref","is-referenced-by-count":11,"title":["Amyloid PET Quantitation and Centiloid Thresholds in the Diagnosis of Alzheimer Disease"],"prefix":"10.1001","volume":"336","author":[{"given":"Ganna","family":"Blazhenets","sequence":"first","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Soleimani-Meigooni","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco"},{"name":"Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Chiotis","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco"},{"name":"Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel E.","family":"Allen","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil D.","family":"Rabinovici","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco"},{"name":"Department of Radiology and Biomedical Imaging, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"La Joie","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Meta-Centiloid Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liana G.","family":"Apostolova","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine, Indianapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breton M.","family":"Asken","sequence":"additional","affiliation":[{"name":"Department of Clinical and Health Psychology, 1Florida Alzheimer\u2019s Disease Research Center, University of Florida, Gainesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Bejanin","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), Facultad de Medicina - Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain"},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammie L. 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