title: Predicting brain-age from multimodal imaging data captures cognitive impairment.
abstract: The disparity between the chronological age of an individual and their brain-age measured based on biological information has the potential to offer clinically relevant biomarkers of neurological syndromes that emerge late in the lifespan. While prior brain-age prediction studies have relied exclusively on either structural or functional brain data, here we investigate how multimodal brain-imaging data improves age prediction. Using cortical anatomy and whole-brain functional connectivity on a large adult lifespan sample (N=2354, age 19-82), we found that multimodal data improves brain-based age prediction, resulting in a mean absolute prediction error of 4.29 years. Furthermore, we found that the discrepancy between predicted age and chronological age captures cognitive impairment. Importantly, the brain-age measure was robust to confounding effects: head motion did not drive brain-based age prediction and our models generalized reasonably to an independent dataset acquired at a different site (N=475). Generalization performance was increased by training models on a larger and more heterogeneous dataset. The robustness of multimodal brain-age prediction to confounds, generalizability across sites, and sensitivity to clinically-relevant impairments, suggests promising future application to the early prediction of neurocognitive disorders.
authors.affiliation: Max Planck Research Group for Neuroanatomy & Connectivity, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany. Electronic address: liem@cbs.mpg.de.
authors.forename: Franziskus
authors.initials: F
authors.lastname: Liem
authors.affiliation: Parietal project team - INRIA, Saclay, France; CEA, DSV, I2BM, Neurospin, Gif-Sur-Yvette, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Varoquaux
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Kynast
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Subproject A1, Faculty of Medicine, Collaborative Research Centre 1052 "Obesity Mechanisms", University of Leipzig, Leipzig, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Beyer
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Kharabian Masouleh
authors.affiliation: Max Planck Research Group for Neuroanatomy & Connectivity, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Neurocomputation and Neuroimaging Unit, Department of Education and Psychology, Free University of Berlin, Berlin, Germany.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Huntenburg
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Leipzig Research Center for Civilization Diseases (LIFE), University of Leipzig, Leipzig, Germany.
authors.forename: Leonie
authors.initials: L
authors.lastname: Lampe
authors.affiliation: Parietal project team - INRIA, Saclay, France; CEA, DSV, I2BM, Neurospin, Gif-Sur-Yvette, France.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rahim
authors.affiliation: Parietal project team - INRIA, Saclay, France; CEA, DSV, I2BM, Neurospin, Gif-Sur-Yvette, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Abraham
authors.affiliation: Computational Neuroimaging Lab, Center for Biomedical Imaging and Neuromodulation, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA; Center for the Developing Brain, Child Mind Institute, New York, NY, USA.
authors.forename: R Cameron
authors.initials: RC
authors.lastname: Craddock
authors.affiliation: Leipzig Research Center for Civilization Diseases (LIFE), University of Leipzig, Leipzig, Germany; Medical Faculty, Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, Germany.
authors.forename: Steffi
authors.initials: S
authors.lastname: Riedel-Heller
authors.affiliation: Leipzig Research Center for Civilization Diseases (LIFE), University of Leipzig, Leipzig, Germany; Medical Faculty, Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Luck
authors.affiliation: Leipzig Research Center for Civilization Diseases (LIFE), University of Leipzig, Leipzig, Germany; Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany; Leipzig Research Center for Civilization Diseases (LIFE), University of Leipzig, Leipzig, Germany.
authors.forename: Matthias L
authors.initials: ML
authors.lastname: Schroeter
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Subproject A1, Faculty of Medicine, Collaborative Research Centre 1052 "Obesity Mechanisms", University of Leipzig, Leipzig, Germany; Leipzig Research Center for Civilization Diseases (LIFE), University of Leipzig, Leipzig, Germany.
authors.forename: Anja Veronica
authors.initials: AV
authors.lastname: Witte
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Subproject A1, Faculty of Medicine, Collaborative Research Centre 1052 "Obesity Mechanisms", University of Leipzig, Leipzig, Germany; Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany; Leipzig Research Center for Civilization Diseases (LIFE), University of Leipzig, Leipzig, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Villringer
authors.affiliation: Max Planck Research Group for Neuroanatomy & Connectivity, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Margulies
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging* / Q000254:growth & development*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000254:growth & development; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000523:psychology; D005260:Female; D019416:Head Movements; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D064847:Multimodal Imaging / Q000379:methods*; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D055815:Young Adult
keywords: Biomarker; Cognition; Head motion; Machine learning