{"doi":"10.1002/ana.26071","title":"<scp>NIA‐AA</scp> Alzheimer's Disease Framework: Clinical Characterization of Stages","abstract":"BACKGROUND: To operationalize the National Institute on Aging - Alzheimer's Association (NIA-AA) Research Framework for Alzheimer's Disease 6-stage continuum of clinical progression for persons with abnormal amyloid. METHODS: The Mayo Clinic Study of Aging is a population-based longitudinal study of aging and cognitive impairment in Olmsted County, Minnesota. We evaluated persons without dementia having 3 consecutive clinical visits. Measures for cross-sectional categories included objective cognitive impairment (OBJ) and function (FXN). Measures for change included subjective cognitive impairment (SCD), objective cognitive change (ΔOBJ), and new onset of neurobehavioral symptoms (ΔNBS). We calculated frequencies of the stages using different cutoff points and assessed stability of the stages over 15 months. RESULTS: Among 243 abnormal amyloid participants, the frequencies of the stages varied with age: 66 to 90% were classified as stage 1 at age 50 but at age 80, 24 to 36% were stage 1, 32 to 47% were stage 2, 18 to 27% were stage 3, 1 to 3% were stage 4 to 6, and 3 to 9% were indeterminate. Most stage 2 participants were classified as stage 2 because of abnormal ΔOBJ only (44-59%), whereas 11 to 21% had SCD only, and 9 to 13% had ΔNBS only. Short-term stability varied by stage and OBJ cutoff points but the most notable changes were seen in stage 2 with 38 to 63% remaining stable, 4 to 13% worsening, and 24 to 41% improving (moving to stage 1). INTERPRETATION: The frequency of the stages varied by age and the precise membership fluctuated by the parameters used to define the stages. The staging framework may require revisions before it can be adopted for clinical trials. 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Wiste","orcid":null,"position":1,"is_corresponding":false},{"id":270815,"name":"Stephen D. Weigand","orcid":"0000-0002-4541-9011","position":2,"is_corresponding":false},{"id":253904,"name":"Julie A. Fields","orcid":"0000-0002-1282-9866","position":3,"is_corresponding":false},{"id":461080,"name":"Yonas E. Geda","orcid":"0000-0003-1187-7230","position":4,"is_corresponding":false},{"id":253918,"name":"Jonathan Graff‐Radford","orcid":"0000-0003-2770-0691","position":5,"is_corresponding":false},{"id":49955,"name":"David S. Knopman","orcid":"0000-0002-6544-066X","position":6,"is_corresponding":false},{"id":253903,"name":"Walter K. Kremers","orcid":"0000-0001-5714-3473","position":7,"is_corresponding":false},{"id":259159,"name":"Val J. Lowe","orcid":"0000-0002-5612-1667","position":8,"is_corresponding":false},{"id":259156,"name":"Mary M. Machulda","orcid":"0000-0003-4834-5967","position":9,"is_corresponding":false},{"id":228538,"name":"Michelle M. Mielke","orcid":"0000-0001-7177-1185","position":10,"is_corresponding":false},{"id":651188,"name":"Nikki H. Stricker","orcid":"0000-0001-9034-1252","position":11,"is_corresponding":false},{"id":270817,"name":"Terry M. Therneau","orcid":"0000-0003-1490-6711","position":12,"is_corresponding":false},{"id":226058,"name":"Prashanthi Vemuri","orcid":"0000-0003-4286-0589","position":13,"is_corresponding":false},{"id":49956,"name":"Clifford R. Jack","orcid":"0000-0001-7916-622X","position":14,"is_corresponding":false},{"id":27599,"name":"Ronald C. Petersen","orcid":"0000-0002-8178-6601","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T23:43:44.759273Z","pmid":"33772866","pmcid":"PMC8131266","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":22.2222,"fair_a":18.75,"fair_i":0.0,"fair_r":16.6667,"fair_zscore":-1.1986,"fair_rationale":{"fair_score":4.17,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":22.22,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"The text does not provide a persistent identifier or any URI for the dataset; the only mention is 'available upon request'.","anchors":["RDA-F1-01D — FAIR Data Maturity Model: 'Data is identified by a persistent identifier' (priorit","RDA-F1-02D — FAIR Data Maturity Model: 'Data is identified by a globally unique identifier'","FsF-F1-02D — F-UJI/FAIRsFAIR: 'Data is assigned a persistent identifier'"],"scored":true,"signal":null},{"key":"f_repository_named","label":"Named repository","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No repository is named as the holder of the data; the only statement is 'available upon request'. 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For clinical / human-subjects data, deposit in dbGaP or the European Genome-phenome Archive (EGA).","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"The text does not provide a persistent identifier or any URI for the dataset; the only mention is 'available upon request'.","gain":16.67,"priority":"essential","scored":true},{"key":"f_repository_named","dimension":"F","label":"Named repository","action":"Deposit the data in a repository registered in re3data/FAIRsharing (a domain repository such as GEO, SRA, dbGaP, PRIDE, or a generalist such as Zenodo, Dryad, Dataverse) and name it explicitly in the paper. A lab website is not an archive: it has no retention commitment and no accession. 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For clinical / human-subjects data, deposit in dbGaP or the European Genome-phenome Archive (EGA).","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"Data from the MCSA, including data from this study, are available upon request.","why":"The only route is a discretionary request to a person, which is not a followable access process.","gain":16.67,"priority":"essential","scored":true},{"key":"r_reuse_license","dimension":"R","label":"Reuse licence","action":"Attach a standard, machine-readable open licence to the deposit — CC0 or CC BY, which is what Horizon Europe and most funders expect — and print the licence identifier in the paper. 'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No licence or reuse terms are stated for the data; the CC-BY-NC-ND licence applies to the article only.","gain":16.67,"priority":"essential","scored":true},{"key":"f_dataset_cited","dimension":"F","label":"Dataset formally cited","action":"Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. 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For sensitive/human clinical / human-subjects data, use a controlled-access repository such as dbGaP or EGA.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Data from the MCSA, including data from this study, are available upon request.","why":"The data are human-subject and the only gatekeeper is the corresponding author, a natural person, with no institutional committee named. [majority verdict 'partial' (4/5 passes agreed)]","gain":0.0,"priority":"useful","scored":false},{"key":"i_qualified_references","dimension":"I","label":"Identifiers for the resources the data depend on","action":"Cite by identifier every resource the data depend on — the source datasets' accessions, the reference build (GRCh38 / GCA_000001405.28), the cohort application number, the code DOI — and register those relations on the dataset record (IsDerivedFrom, IsSupplementTo). A name is not a link: it cannot be resolved, versioned, or followed by a machine.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No identifier (DOI, accession, RRID, or database version) is given for any external resource used; references are to articles only.","gain":0.0,"priority":"useful","scored":false},{"key":"a_timeline_retention","dimension":"A","label":"Availability timing & retention","action":"State when the data become available AND how long they will be retained — cite the repository's preservation policy. NIH DMS Element 4 asks for both; most papers give neither.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No sentence addresses the timing or persistence of the data's availability.","gain":0.0,"priority":"useful","scored":false}],"suggestions":["Mint or cite a persistent identifier for the dataset — a repository DOI or an accession from a registered repository — and print it in the paper. A bare URL is not persistent: it is the single most common cause of a dead data link five years after publication. For clinical / human-subjects data, deposit in dbGaP or the European Genome-phenome Archive (EGA).","Deposit the data in a repository registered in re3data/FAIRsharing (a domain repository such as GEO, SRA, dbGaP, PRIDE, or a generalist such as Zenodo, Dryad, Dataverse) and name it explicitly in the paper. A lab website is not an archive: it has no retention commitment and no accession. For clinical / human-subjects data, deposit in dbGaP or the European Genome-phenome Archive (EGA).","Remove the precondition or justify it. Release the data at publication with no embargo, no registration wall, and no approval step — NIH's zero-embargo public- access rule (NOT-OD-25-101) has already made 'available at publication' the federal baseline for the article; the data should not lag behind it. For clinical / human-subjects data, deposit in dbGaP or the European Genome-phenome Archive (EGA).","Attach a standard, machine-readable open licence to the deposit — CC0 or CC BY, which is what Horizon Europe and most funders expect — and print the licence identifier in the paper. 'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the clinical / human-subjects repository accession (e.g. from dbGaP or the European Genome-phenome Archive (EGA)) in the reference list."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v8","fulltext_source":"epmc_xml"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v8","fair_fulltext_source":"epmc_xml","fair_has_llm":true,"fair_computed_at":"2026-07-20T11:12:43.200173Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}