Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia


Timothy Rittman, University of Cambridge
Robin Borchert, University of Cambridge
Simon Jones, University of Cambridge
John van Swieten, Erasmus MC
Barbara Borroni, Università degli Studi di Brescia
Daniela Galimberti, Università degli Studi di Milano
Mario Masellis, Sunnybrook Health Sciences Centre
Maria Carmela Tartaglia, Tanz Centre for Research in Neurodegenerative Diseases
Caroline Graff, Karolinska Institutet
Fabrizio Tagliavini, Foundation IRCCS Neurological Institute "C. Besta"
Giovanni B. Frisoni, Université de Genève
Robert Laforce, Université Laval
Elizabeth Finger, The University of Western Ontario
Alexandre Mendonça, Faculdade de Medicina, Universidade de Lisboa
Sandro Sorbi, Università degli Studi di Firenze
Jonathan D. Rohrer, UCL Queen Square Institute of Neurology
James B. Rowe, University of Cambridge
Sónia Afonso, Universidade de Coimbra, Instituto de Ciências Nucleares Aplicadas à Saude
Maria Rosario Almeida, Universidade de Coimbra, Faculdade de Medicina
Sarah Anderl-Straub, Universität Ulm
Christin Andersson, Karolinska Institutet
Anna Antonell, Hospital Clinic Barcelona
Silvana Archetti, Spedali Civili Di Brescia
Andrea Arighi, Ospedale Maggiore Policlinico Milano
Mircea Balasa, Hospital Clinic Barcelona
Myriam Barandiaran, Osakidetza, Donostia University Hospital
Nuria Bargalló, Hospital Clinic Barcelona
Robart Bartha, The University of Western Ontario
Benjamin Bender, Universität Tübingen
Luisa Benussi, IRCCS Centro San Giovanni di Dio Fatebenefratelli
Valentina Bessi, Università degli Studi di Firenze
Giuliano Binetti, IRCCS Centro San Giovanni di Dio Fatebenefratelli

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Neurobiology of Aging



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© 2019 The Authors The presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied 172 people from families carrying genetic abnormalities in C9orf72, MAPT, or PGRN. Networks were extracted from functional MRI data and assessed using graph theoretical analysis. We found that despite loss of both brain volume and functional connections, there is maintenance of an efficient topological organization of the brain's functional network in the years leading up to the estimated age of frontotemporal dementia symptom onset. After this point, functional network efficiency declines markedly. Reduction in connectedness was most marked in highly connected hub regions. Measures of topological efficiency of the brain's functional network and organization predicted cognitive dysfunction in domains related to symptomatic frontotemporal dementia and connectivity correlated with brain volume loss in frontotemporal dementia. We propose that maintaining the efficient organization of the brain's functional network supports cognitive health even as atrophy and connectivity decline presymptomatically.

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