{"doi":"10.1002/alz.14492","title":"A multi‐cohort study of longitudinal and cross‐sectional Alzheimer's disease biomarkers in cognitively unimpaired older adults","abstract":"INTRODUCTION: The generalizability of neuroimaging and cognitive biomarkers in their sensitivity to detect preclinical Alzheimer's disease (AD) and power to predict progression in large, multisite cohorts remains unclear. METHOD: Longitudinal demographics, T1-weighted magnetic resonance imaging (MRI), and cognitive scores of 3036 cognitively unimpaired (CU) older adults (amyloid beta [Aβ]-negative/positive [A-/A+]: 1270/1558) were included. Cross-sectional and longitudinal cognition and medial temporal lobe (MTL) structural measures were extracted. Cross-sectional MTL tau burden (T) was computed from tau positron emission tomography (N = 1095). RESULTS: We found cross-sectional tau and longitudinal structural biomarkers best separated A+ CU from A- CU. A-T+ CU had significantly faster neurodegeneration rate compared to A-T- CU. MTL tau was significantly correlated with MRI and cognitive biomarkers regardless of Aβ status. MTL tau, MRI, and cognition provided complementary information about disease progression. DISCUSSION: This large multisite study replicates prior findings in CU older adults, supporting the utility of neuroimaging and cognitive biomarkers in preclinical AD clinical trials and normal aging studies. HIGHLIGHTS: We investigated neuroimaging and cognitive biomarkers in 3036 cognitively unimpaired (CU) participants. Medial temporal lobe (MTL) tau and longitudinal MTL atrophy best separate amyloid beta positive (A+) CU from amyloid beta negative (A-) CU. A- tau positive (T+) CU had a significantly faster neurodegeneration rate compared to A-T- CU. MTL tau correlated with structural magnetic resonance imaging (MRI) and cognition regardless of amyloid beta status. Combined baseline MTL tau, MRI, and cognition best predict Alzheimer's disease progression.","journal":"Alzheimer s & Dementia","year":2025,"id":515670,"datarank":0.48945100268534103,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.10470859906611044,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.10470859906611044,"corpus_percentile":60.91900673009979,"corpus_rank":5053,"citation_count":12,"citer_count":8,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.8768,"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":265855,"name":"Sandhitsu R. 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