Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia

the Genetic FTD Initiative, GENFI, Kamen A. Tsvetanov*, Stefano Gazzina, P. Simon Jones, John van Swieten, Barbara Borroni, Raquel Sanchez-Valle, Fermin Moreno, Robert Laforce, Caroline Graff, Matthis Synofzik, Daniela Galimberti, Mario Masellis, Maria Carmela Tartaglia, Elizabeth Finger, Rik Vandenberghe, Alexandre de Mendonça, Fabrizio Tagliavini, Isabel Santana, Simon DucharmeChris Butler, Alexander Gerhard, Adrian Danek, Johannes Levin, Markus Otto, Giovanni Frisoni, Roberta Ghidoni, Sandro Sorbi, Jonathan D. Rohrer, James B. Rowe, Sónia Afonso, Maria Rosario Almeida, Sarah Anderl-Straub, Christin 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, Carlos Ferreira, Carolina Maruta

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)500-514
Number of pages15
JournalAlzheimer's and Dementia
Issue number3
Publication statusPublished - Mar 2021
Externally publishedYes


  • Frontotemporal dementia (FTD)
  • Functional magnetic resonance imaging (fMRI)
  • Network connectivity
  • Presymptomatic


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