Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia

Timothy Rittman, Robin Borchert, Simon Jones, John van Swieten, Barbara Borroni, Daniela Galimberti, Mario Masellis, Maria Carmela Tartaglia, Caroline Graff, Fabrizio Tagliavini, Giovanni B. Frisoni, Robert Laforce, Elizabeth Finger, Alexandre Mendonça, Sandro Sorbi, Jonathan D. Rohrer, James B. Rowe, S. nia Afonso, Maria Rosario Almeida, Sarah Anderl-StraubChristin Andersson, Anna Antonell, Silvana Archetti, Andrea Arighi, Mircea Balasa, Myriam Barandiaran, Nuria Bargalló, Robart Bartha, Benjamin Bender, Luisa Benussi, Valentina Bessi, Giuliano Binetti, Sandra Black, Martina Bocchetta, Sergi Borrego-Ecija, Jose Bras, Rose Bruffaerts, Paola Caroppo, David Cash, Miguel Castelo-Branco, Rhian Convery, Thomas Cope, Maura Cosseddu, Nick Fox, Lize Jiskoot, Jessica Panman, Yolande Pijnenburg, Lize Jiskoot, Jessica Panman, Sara Prioni, Beatriz Santiago, David Tang-Wai, Michele Veldsman, Ana Verdelho, Jorge Villanua, Jason Warren, Carlo Wilke, Ione Woollacott, Elisabeth Wlasich, Henrik Zetterberg, Miren Zulaica, the Genetic Frontotemporal dementia Initiative (GENFI)

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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.
Original languageEnglish
Pages (from-to)169-177
Number of pages9
JournalNeurobiology of Aging
Publication statusPublished - 1 May 2019

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