Global network and local vulnerabilities underlie brain atrophy across Parkinson's disease stages.
Global network and local vulnerabilities underlie brain atrophy across Parkinson's disease stages.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Montréal, CA · Author affiliation
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada H3A 2B4.Location evidence
Lancaster, GB · Author affiliation
Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4AT, UK.Location evidence
Manchester, GB · Author affiliation
Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK.Location evidence
Amsterdam, NL · Author affiliation
Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, The Netherlands.Location evidence
London, GB · Author affiliation
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.Location evidence
BR · Author affiliation · country only
Department of Neurology, University of Campinas-UNICAMP, Campinas 13083-888, Brazil.Location evidence
Christchurch, NZ · Author affiliation
Te Kura Mahi ā-Hirikapo, School of Psychology, Speech and Hearing, University of Canterbury, Christchurch 8041, New Zealand.Location evidence
Bern, CH · Author affiliation
Department of Neurology, Inselspital, University Hospital Bern, University of Bern, Bern CH-3010, Switzerland.Location evidence
Nijmegen, NL · Author affiliation
Department of Neurology and Center of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6525 GC, The Netherlands.Location evidence
Charlottesville, US · Author affiliation
Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22903, USA.Location evidence
Liège, BE · Author affiliation
MoVeRe Group, GIGA-CRC In Vivo Imaging, University of Liège, Liège 4000, Belgium.Location evidence
Oxford, GB · Author affiliation
Division of Clinical Neurology, Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, Nuffield, University of Oxford, Oxford OX3 9DU, UK.Location evidence
Marina, US · Author affiliation
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90033, USA.Location evidence
Philadelphia, US · Author affiliation
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.Location evidence
AU · Author affiliation · country only
QIMR Berghofer Medical Research Institute, Queensland 4006, Australia.Location evidence
Rome, IT · Author affiliation
Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome 00179, Italy.Location evidence
Palo Alto, US · Author affiliation
Department of Neurology & Neurological Sciences, Movement Disorders, Stanford University, Palo Alto, CA 94304, USA.Location evidence
Milan, IT · Author affiliation
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 20122, Italy.Location evidence
Graz, AT · Author affiliation
Department of Neurology, Medical University of Graz, Graz 8036, Austria.Location evidence
San Francisco, US · Author affiliation
Department of Radiology and Biomedical Imaging, University of California SanFrancisco, San Francisco, CA 94143, USA.Location evidence
Taoyuan, TW · Author affiliation
Healthy Ageing Research Center, Chang Gung University, Taoyuan City 33302, Taiwan.Location evidence
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Original abstract
Parkinson's disease 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, few studies have assessed these biological frameworks in large patient samples across disease stages. Analysing the largest imaging cohort in Parkinson's disease to date (n = 3096 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 Parkinson's disease to be associated with advancing disease stage, longer time since diagnosis and poorer global cognition. Structural brain connectivity best explained cortical atrophy patterns in Parkinson's disease 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 Parkinson's disease. In summary, this study demonstrates in a well-powered sample that structural brain abnormalities in Parkinson's disease across disease stages and within individual patients are influenced by both network spread and local vulnerability.