[en] Parkinson's disease (PD) is associated with extensive structural brain changes. Recent work has proposed that the spatial pattern of disease pathology is shaped by both network spread and local vulnerability. However, only few studies assessed these biological frameworks in large patient samples across disease stages. Analyzing the largest imaging cohort in PD to date (N = 3,096 patients), we investigated the roles of network architecture and local brain features by relating regional abnormality maps to normative profiles of connectivity, intrinsic networks, cytoarchitectonics, neurotransmitter receptor densities, and gene expression. We found widespread cortical and subcortical atrophy in PD to be associated with advancing disease stage, longer time since diagnosis, and poorer global cognition. Structural brain connectivity best explained cortical atrophy patterns in PD and across disease stages. These patterns were robust among individual patients. The precuneus, lateral temporal cortex, and amygdala were identified as likely network-based epicentres, with high convergence across disease stages. Individual epicentres varied significantly among patients, yet they consistently localized to the default mode and limbic networks. Furthermore, we showed that regional overexpression of genes implicated in synaptic structure and signalling conferred increased susceptibility to brain atrophy in PD. In summary, this study demonstrates in a well-powered sample that structural brain abnormalities in PD across disease stages and within individual patients are influenced by both network spread and local vulnerability.
Disciplines :
Neurology
Author, co-author :
Vo, Andrew; Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada
Tremblay, Christina; Department of Medicine, Centre for Advanced Research in Sleep Medicine, University of Montreal, Montreal, Canada
Rahayel, Shady; Department of Medicine, Centre for Advanced Research in Sleep Medicine, University of Montreal, Montreal, Canada
Al-Bachari, Sarah; Faculty of Health and Medicine, Lancaster University, Lancaster, UK ; Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
Berendse, Henk W; Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands
Bright, Joanna K; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
Cendes, Fernando ; Department of Neurology, University of Campinas-UNICAMP, Campinas, Brazil
d'Angremont, Emile; Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands
Dalrymple-Alford, John C; Te Kura Mahi ā-Hirikapo | School of Psychology, Speech and Hearing, University of Canterbury, Christchurch, New Zealand ; New Zealand Brain Research Institute, Christchurch, New Zealand
Debove, Ines; Department of Neurology, Inselspital, University of Bern, Bern, Switzerland
Dirkx, Michiel F; Department of Neurology and Center of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands ; Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands
Druzgal, Jason; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA
Garraux, Gaëtan ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie du système nerveux
Helmich, Rick C ; Department of Neurology and Center of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands ; Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands
Hu, Michele; Division of Clinical Neurology, Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, Nuffield, University of Oxford, Oxford, UK
Jahanshad, Neda; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
Johansson, Martin E; Department of Neurology and Center of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands ; Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands
Klein, Johannes C ; Division of Clinical Neurology, Department of Clinical Neurosciences, Oxford Centre for Integrative Neuroimaging, Oxford Parkinson's Disease Centre, Nuffield, University of Oxford, Oxford, UK
Laansma, Max A; Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands
McMillan, Corey T ; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
Melzer, Tracy R; Te Kura Mahi ā-Hirikapo | School of Psychology, Speech and Hearing, University of Canterbury, Christchurch, New Zealand ; New Zealand Brain Research Institute, Christchurch, New Zealand ; Department of Medicine, University of Otago, Christchurch, New Zealand ; Pacific Radiology Canterbury, Christchurch, New Zealand
Misic, Bratislav; Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada
Mosley, Philip; QIMR Berghofer Medical Research Institute, Queensland, Australia
Owens-Walton, Conor ; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
Parkes, Laura M ; Division of Psychology, Communication and Human Neuroscience, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK ; Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance & University of Manchester, Manchester, UK
Pellicano, Clelia; Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy
Piras, Fabrizio; Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy
Poston, Kathleen L ; Department of Neurology & Neurological Sciences, Movement Disorders, Stanford University, Palo Alto, CA, USA
Rango, Mario; Excellence Interdepartmental Center for Advanced MR Techniques and Department of Neurosciences, Neurology Unit, Parkinson's Disease Center, Fondazione Cà Granda, IRCCS, Ospedale Policlinico, University of Milan, Milan, Italy
Rummel, Christian; Support Center for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern, Switzerland
Schwingenschuh, Petra; Department of Neurology, Medical University of Graz, Graz, Austria
Suette, Melanie; Department of Neurology, Medical University of Graz, Graz, Austria
Thompson, Paul M ; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
Tosun, Duygu; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA
Tsai, Chih-Chien; Healthy Ageing Research Center, Chang Gung University, Taoyuan City
van Balkom, Tim D ; Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands ; Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands
van den Heuvel, Odile A; Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands ; Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
van der Werf, Ysbrand D; Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands
van Heese, Eva M ; Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands
Vriend, Chris ; Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands ; Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands ; Amsterdam Neuroscience, Brain Imaging, Amsterdam, The Netherlands
Wang, Jiun-Jie; Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan City, Taiwan
Wiest, Roland; Support Center for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern, Switzerland
Yasuda, Clarissa; Department of Neurology, University of Campinas-UNICAMP, Campinas, Brazil ; Brazilian Institute of Neuroscience and Neurotechnology, Campinas, Brazil
Dagher, Alain; Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada
