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Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia.
Journal article

Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia.

  • Rittman T Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. Electronic address: tr332@medschl.cam.ac.uk.
  • Borchert R Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • Jones S Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • van Swieten J Alzheimercentrum, Erasmus Medical Center, Rotterdam, the Netherlands.
  • Borroni B Department of Clinical and Experimental Sciences, University of Brescia, Italy.
  • Galimberti D Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
  • Masellis M Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Canada.
  • Tartaglia MC Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.
  • Graff C Department NVS, Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
  • Tagliavini F Istituto Neurologico Carlo Besta, Milan, Italy.
  • Frisoni GB Department of Psychiatry, University Hospitals and University of Geneva, Geneva, Switzerland; Neuroimaging and Epidemiology Unit, IRCCS San Giovanni di Dio Fatebenefratelli Brescia, Brescia, Italy.
  • Laforce R Faculty of Medicine, Université Laval, Quebec, Canada.
  • Finger E Department of Clinical Neurological Sciences, University of Western Ontario, Ontario, Canada.
  • Mendonça A Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
  • Sorbi S Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy; IRCCS Don Gnocchi, Florence, Italy.
  • Rohrer JD Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
  • Rowe JB Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
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  • 2019-03-05
Published in:
  • Neurobiology of aging. - 2019
Cognition
Connectivity
Frontotemporal dementia
Functional imaging
Genetics
Adult
Aged
Atrophy
Brain
C9orf72 Protein
Cognition
Female
Frontotemporal Dementia
Heterozygote
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Nerve Net
Neuroimaging
Organ Size
tau Proteins
English 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.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://sonar.ch/global/documents/138054
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