Kamen A Tsvetanov1,2, Stefano Gazzina1,3, P Simon Jones1, John van Swieten3, Barbara Borroni4, Raquel Sanchez-Valle5, Fermin Moreno6,7, Robert Laforce8, Caroline Graff9,10, Matthis Synofzik11,12, Daniela Galimberti13,14, Mario Masellis15, Maria Carmela Tartaglia16, Elizabeth Finger17, Rik Vandenberghe18,19, Alexandre de Mendonça20, Fabrizio Tagliavini21, Isabel Santana22,23,24, Simon Ducharme25,26, Chris Butler27, Alexander Gerhard28,29, Adrian Danek30, Johannes Levin31, Markus Otto32, Giovanni Frisoni33,34, Roberta Ghidoni35, Sandro Sorbi36,37, Jonathan D Rohrer38, James B Rowe1,2. 1. Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. 2. Cambridge Centre for Ageing and Neuroscience (Cam-CAN), University of Cambridge and MRC Cognition and Brain Sciences Unit, Cambridge, UK. 3. Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands. 4. Centre for Neurodegenerative Disorders, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. 5. 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. 6. Cognitive Disorders Unit, Department of Neurology, Hospital Universitario Donostia, San Sebastian, Gipuzkoa, Spain. 7. Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain. 8. Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, and Faculté de Médecine, Université Laval, Québec, Canada. 9. Department NVS, Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Stockholm, Sweden. 10. Unit for Hereditary Dementias, Theme Aging, Karolinska University Hospital-Solna, Stockholm, Sweden. 11. Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research & Center of Neurology, University of Tübingen, Germany. 12. German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. 13. Centro Dino Ferrari, University of Milan, Milan, Italy. 14. Fondazione IRCSS Ca' Granda, Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy. 15. LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Department of Medicine (Neurology), University of Toronto, Toronto, Ontario, Canada. 16. Tanz Centre for Research in Neurodegenerative Disease, Toronto Western Hospital, Toronto, Ontario, Canada. 17. Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada. 18. Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium. 19. Neurology Service, University Hospitals Leuven, Leuven, Belgium. 20. Laboratory of Neurosciences, Faculty of Medicine, Institute of Molecular Medicine, University of Lisbon, Lisbon, Portugal. 21. Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta, Milan, Italy. 22. Neurology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. 23. Faculty of Medicine, University of Coimbra, Coimbra, Portugal. 24. Centre of Neurosciences and Cell biology, Universidade de Coimbra, Coimbra, Portugal. 25. Department of Psychiatry, McGill University Health Centre, McGill University, Montreal, Canada. 26. McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada. 27. Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK. 28. Division of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK. 29. Departments of Geriatric Medicine and Nuclear Medicine, University of Duisburg-Essen, Germany. 30. Neurologische Klinik und Poliklinik, German Center for Neurodegenerative Diseases (DZNE), Ludwig-Maximilians-Universität, Munich, Munich, Germany. 31. German Center for Neurodegenerative Diseases, Munich Cluster for Systems Neurology (Synergy), Munich, Germany. 32. Department of Neurology, University Hospital Ulm, Ulm, Germany. 33. Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. 34. Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland. 35. Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. 36. Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy. 37. Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) "Fondazione Don Carlo Gnocchi", Florence, Italy. 38. Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
Abstract
INTRODUCTION: The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial frontotemporal dementia (FTD). METHODS: We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset. RESULTS: There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviorally relevant structural and functional network differences. Structure-function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non-carriers, and increased with proximity to the expected onset of disease. DISCUSSION: Our findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance.
INTRODUCTION: The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial frontotemporal dementia (FTD). METHODS: We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset. RESULTS: There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviorally relevant structural and functional network differences. Structure-function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non-carriers, and increased with proximity to the expected onset of disease. DISCUSSION: Our findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance.
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Authors: Phoebe H Foster; Lucy L Russell; Georgia Peakman; Rhian S Convery; Arabella Bouzigues; Caroline V Greaves; Martina Bocchetta; David M Cash; John C van Swieten; Lize C Jiskoot; Fermin Moreno; Raquel Sanchez-Valle; Robert Laforce; Caroline Graff; Mario Masellis; Carmela Tartaglia; James B Rowe; Barbara Borroni; Elizabeth Finger; Matthis Synofzik; Daniela Galimberti; Rik Vandenberghe; Alexandre de Mendonça; Chris R Butler; Alex Gerhard; Simon Ducharme; Isabelle Le Ber; Fabrizio Tagliavini; Isabel Santana; Florence Pasquier; Johannes Levin; Adrian Danek; Markus Otto; Sandro Sorbi; Jonathan D Rohrer Journal: Cortex Date: 2022-02-09 Impact factor: 4.644