TY - JOUR TI - Biological brain age prediction using machine learning on structural neuroimaging data: Multi-cohort validation against biomarkers of Alzheimer’s disease and neurodegeneration stratified by sex AU - Cumplido-Mayoral, Irene AU - García-Prat, Marina AU - Operto, Grégory AU - Falcon, Carles AU - Shekari, Mahnaz AU - Cacciaglia, Raffaele AU - Milà-Alomà, Marta AU - Lorenzini, Luigi AU - Ingala, Silvia AU - Meije Wink, Alle AU - Mutsaerts, Henk JMM AU - Minguillón, Carolina AU - Fauria, Karine AU - Molinuevo, José Luis AU - Haller, Sven AU - Chetelat, Gael AU - Waldman, Adam AU - Schwarz, Adam J AU - Barkhof, Frederik AU - Suridjan, Ivonne AU - Kollmorgen, Gwendlyn AU - Bayfield, Anna AU - Zetterberg, Henrik AU - Blennow, Kaj AU - Suárez-Calvet, Marc AU - Vilaplana, Verónica AU - Gispert, Juan Domingo AU - ALFA study AU - EPAD study AU - ADNI study AU - OASIS study A2 - Miller, Karla L A2 - Wong, Ma-Li A2 - Boyle, Rory A2 - Cole, James VL - 12 PY - 2023 DA - 2023/04/17 SP - e81067 C1 - eLife 2023;12:e81067 DO - 10.7554/eLife.81067 UR - https://doi.org/10.7554/eLife.81067 AB - Brain-age can be inferred from structural neuroimaging and compared to chronological age (brain-age delta) as a marker of biological brain aging. Accelerated aging has been found in neurodegenerative disorders like Alzheimer’s disease (AD), but its validation against markers of neurodegeneration and AD is lacking. Here, imaging-derived measures from the UK Biobank dataset (N=22,661) were used to predict brain-age in 2,314 cognitively unimpaired (CU) individuals at higher risk of AD and mild cognitive impaired (MCI) patients from four independent cohorts with available biomarker data: ALFA+, ADNI, EPAD, and OASIS. Brain-age delta was associated with abnormal amyloid-β, more advanced stages (AT) of AD pathology and APOE-ε4 status. Brain-age delta was positively associated with plasma neurofilament light, a marker of neurodegeneration, and sex differences in the brain effects of this marker were found. These results validate brain-age delta as a non-invasive marker of biological brain aging in non-demented individuals with abnormal levels of biomarkers of AD and axonal injury. KW - brain age prediction KW - neuroimaging KW - alzheimer's disease JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -