eLife (Apr 2023)
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
- Irene Cumplido-Mayoral,
- Marina García-Prat,
- Grégory Operto,
- Carles Falcon,
- Mahnaz Shekari,
- Raffaele Cacciaglia,
- Marta Milà-Alomà,
- Luigi Lorenzini,
- Silvia Ingala,
- Alle Meije Wink,
- Henk JMM Mutsaerts,
- Carolina Minguillón,
- Karine Fauria,
- José Luis Molinuevo,
- Sven Haller,
- Gael Chetelat,
- Adam Waldman,
- Adam J Schwarz,
- Frederik Barkhof,
- Ivonne Suridjan,
- Gwendlyn Kollmorgen,
- Anna Bayfield,
- Henrik Zetterberg,
- Kaj Blennow,
- Marc Suárez-Calvet,
- Verónica Vilaplana,
- Juan Domingo Gispert,
- ALFA study,
- EPAD study,
- ADNI study,
- OASIS study
Affiliations
- Irene Cumplido-Mayoral
- ORCiD
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain
- Marina García-Prat
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain
- Grégory Operto
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, France
- Carles Falcon
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain
- Mahnaz Shekari
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
- Raffaele Cacciaglia
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, France
- Marta Milà-Alomà
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, France
- Luigi Lorenzini
- Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Silvia Ingala
- Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Alle Meije Wink
- Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Henk JMM Mutsaerts
- ORCiD
- Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Carolina Minguillón
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, France
- Karine Fauria
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, France
- José Luis Molinuevo
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain
- Sven Haller
- ORCiD
- CIRD Centre d'Imagerie Rive Droite, Geneva, Switzerland
- Gael Chetelat
- Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of Neurological Disorders", Institut Blood and Brain, Cyceron, France
- Adam Waldman
- Centre for Dementia Prevention, Edinburgh Imaging, and UK Dementia Research Institute at The University of Edinburgh, Edinburgh, United Kingdom
- Adam J Schwarz
- ORCiD
- Takeda Pharmaceutical Company Ltd, Cambridge, United States
- Frederik Barkhof
- Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Institutes of Neurology and Healthcare Engineering, University College London, London, United Kingdom
- Ivonne Suridjan
- Roche Diagnostics International Ltd, Rotkreuz, Switzerland
- Gwendlyn Kollmorgen
- Roche Diagnostics GmbH, Penzberg, Germany
- Anna Bayfield
- Roche Diagnostics GmbH, Penzberg, Germany
- Henrik Zetterberg
- Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, United Kingdom; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China; UK Dementia Research Institute at UCL, London, United Kingdom
- Kaj Blennow
- Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
- Marc Suárez-Calvet
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, France; Servei de Neurologia, Hospital del Mar, Barcelona, Spain
- Verónica Vilaplana
- ORCiD
- Department of Signal Theory and Communications, Universitat Politècnica de Catalunya, Barcelona, Spain
- Juan Domingo Gispert
- ORCiD
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain
- ALFA study
- EPAD study
- ADNI study
- OASIS study
- DOI
- https://doi.org/10.7554/eLife.81067
- Journal volume & issue
-
Vol. 12
Abstract
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.
Keywords
