{"doi":"10.1001/jama.2025.7817","title":"Frequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity","abstract":"Importance: Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective: To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants: Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures: Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration- and European Medicines Agency-approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures: Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results: Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET-positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET-positive/tau PET-negative (17% [95% CI, 13%-22%]) and Aβ PET-negative/tau PET-negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET-positive/tau PET-positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance: In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.","journal":"JAMA","year":2025,"id":509079,"datarank":0.8460409321847298,"base_score":3.970291913552122,"endowment":3.970291913552122,"self_citation_contribution":0.5955437870328184,"citation_network_contribution":0.25049714515191135,"self_endowment_contribution":0.5955437870328184,"citer_contribution":0.25049714515191135,"corpus_percentile":null,"corpus_rank":null,"citation_count":52,"citer_count":40,"citers_with_citation_signal":13,"citers_with_endowment":13,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":503525,"name":"Fiona Heeman","orcid":"0000-0001-7769-8329","position":1,"is_corresponding":false},{"id":318669,"name":"Sheelakumari Raghavan","orcid":"0000-0001-8652-7011","position":2,"is_corresponding":false},{"id":754789,"name":"Alejandro Costoya‐Sánchez","orcid":"0000-0002-5072-1282","position":3,"is_corresponding":false},{"id":1361795,"name":"Martijn van Essen","orcid":"0000-0002-2257-1651","position":4,"is_corresponding":false},{"id":1361796,"name":"Ismini Mainta","orcid":"0000-0001-5296-0116","position":5,"is_corresponding":false},{"id":232606,"name":"Valle Camacho","orcid":"0000-0003-0748-0847","position":6,"is_corresponding":false},{"id":1362849,"name":"Omar Darío Rodríguez-Fonseca","orcid":null,"position":7,"is_corresponding":false},{"id":348237,"name":"Jesús Silva‐Rodríguez","orcid":"0000-0002-5196-0103","position":8,"is_corresponding":false},{"id":872714,"name":"Andrés Perissinotti","orcid":"0000-0003-4190-2425","position":9,"is_corresponding":false},{"id":1361797,"name":"Yuna Gu","orcid":"0009-0007-3200-3977","position":10,"is_corresponding":false},{"id":1362850,"name":"Jihwan Yun","orcid":"0000-0002-2436-4947","position":11,"is_corresponding":false},{"id":1361798,"name":"Débora Elisa Peretti","orcid":"0000-0002-3033-8817","position":12,"is_corresponding":false},{"id":635110,"name":"Federica Ribaldi","orcid":"0000-0001-9208-4472","position":13,"is_corresponding":false},{"id":297174,"name":"Emma M. 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