Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia.

Autor: Bussy A; Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Quebec, Canada.; Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.; Integrated Program in Neuroscience, McGill University, Montreal, Canada., Levy JP; Integrated Program in Neuroscience, McGill University, Montreal, Canada.; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada., Best T; Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Quebec, Canada.; Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.; Integrated Program in Neuroscience, McGill University, Montreal, Canada., Patel R; Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Quebec, Canada.; Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.; Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada., Cupo L; Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Quebec, Canada.; Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.; Integrated Program in Neuroscience, McGill University, Montreal, Canada., Van Langenhove T; Department of Neurology, Ghent University Hospital, Ghent, Belgium., Nielsen JE; Neurogenetics Clinic & Research Lab, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Pijnenburg Y; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Waldö ML; Division of Clinical Sciences Helsingborg, Department of Clinical Sciences Lund, Lund University, Lund, Sweden., Remes AM; Research Unit of Clinical Medicine, Neurology, University of Oulu, Finland.; Medical Research Center, Oulu University Hospital, Oulu, Finland., Schroeter ML; Clinic for Cognitive Neurology, University Clinic Leipzig, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.; Clinic for Cognitive Neurology, University Clinic Leipzig, Leipzig, Germany., Santana I; University Hospital of Coimbra (HUC), Neurology Service, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.; Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal., Pasquier F; Universite de Lille, Lille, France.; Inserm 1172, Lille, France.; CHU, CNR-MAJ, Labex Distalz, Lille, France., Otto M; Department of Neurology, University of Ulm, Ulm, Germany., Danek A; Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, Munich, Germany., Levin J; Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, Munich, Germany.; Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany., Le Ber I; Sorbonne Université, Paris Brain Institute-Institut du Cerveau-ICM, Inserm U1127, Paris, France.; Centre de référence des démences rares ou précoces, IM2A, Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France.; Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France., Vandenberghe R; Department of Neurosciences, Laboratory for Cognitive Neurology, Leuven, Belgium.; Neurology Service, University Hospitals Leuven, Leuven, Belgium.; Leuven Brain Institute, KU Leuven, Leuven, Belgium., Synofzik M; Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany., Moreno F; Neuroscience Area, Biodonostia Health Research Institute, San Sebastian, Spain.; Cognitive Disorders Unit, Department of Neurology, Donostia University Hospital, San Sebastian, Gipuzkoa, Spain., de Mendonça A; Faculty of Medicine, University of Lisbon, Lisbon, Portugal., Sanchez-Valle R; Alzheimer's disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacións Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain., Laforce R; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, and Faculté de Médecine, Université Laval, Quebec, Canada., Langheinrich T; Division of Neuroscience, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK.; Cerebral Function Unit, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK., Gerhard A; Division of Neuroscience, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK.; Departments of Geriatric Medicine and Nuclear Medicine, University of Duisburg, Essen, Germany., Graff C; Center for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Bioclinicum, Karolinska Institutet, Solna, Sweden.; Unit for Hereditary Dementias, Theme Inflammation and Aging, Karolinska University Hospital, Solna, Sweden., Butler CR; Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK.; Department of Brain Sciences, Imperial College London, London, UK., Sorbi S; Department of Neurofarba, University of Florence, Florence, Italy.; IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy., Jiskoot L; Department of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands., Seelaar H; Department of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands., van Swieten JC; Department of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands., Finger E; Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada., Tartaglia MC; Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada., Masellis M; Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Canada., Tiraboschi P; Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Galimberti D; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.; Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy., Borroni B; Centre for Neurodegenerative Disorders, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy., Rowe JB; Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust and Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK., Bocchetta M; Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.; Centre for Cognitive and Clinical Neuroscience, Division of Psychology, Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London, London, UK., Rohrer JD; Munich Cluster of Systems Neurology, Munich, Germany., Devenyi GA; Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Quebec, Canada.; Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada., Chakravarty MM; Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Quebec, Canada.; Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.; Integrated Program in Neuroscience, McGill University, Montreal, Canada.; Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada.; Department of Psychiatry, McGill University, Montreal, Quebec, Canada., Ducharme S; Integrated Program in Neuroscience, McGill University, Montreal, Canada.; Department of Psychiatry, McGill University, Montreal, Quebec, Canada.; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Jazyk: angličtina
Zdroj: Human brain mapping [Hum Brain Mapp] 2023 May; Vol. 44 (7), pp. 2684-2700. Date of Electronic Publication: 2023 Mar 09.
DOI: 10.1002/hbm.26220
Abstrakt: Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.
(© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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