Neurodevelopmental effects of genetic frontotemporal dementia in young adult mutation carriers

• Author(s): Finger, Elizabeth ; Malik, Rubina ; Bocchetta, Martina ; Coleman, Kristy ; Graff, Caroline ; Borroni, Barbara ; Masellis, Mario ; Laforce, Robert ; Greaves, Caroline V. ; Russell, Lucy L. ; Convery, Rhian S. ; Bouzigues, Arabella ; Cash, David M. ; Otto, Markus ; Synofzik, Matthis ; Rowe, James B. ; Galimberti, Daniela ; Tiraboschi, Pietro ; Bartha, Robert ; Shoesmith, Christen ; Tartaglia, Maria Carmela ; van Swieten, John C. ; Seelaar, Harro ; Jiskoot, Lize C. ; Sorbi, Sandro ; Butler, Chris R. ; Gerhard, Alexander ; Sanchez-Valle, Raquel ; De Mendonça, Alexandre ; Moreno, Fermin ; Vandenberghe, Rik ; Le Ber, Isabelle ; Levin, Johannes ; Pasquier, Florence ; Santana, Isabel ; Rohrer, Jonathan D. ; Ducharme, Simon ; Esteve, Aitana Sogorb ; Heller, Carolin ; Thomas, David L. ; Todd, Emily G. ; Nicholas, Jennifer ; Benotmane, Hanya ; Zetterberg, Henrik ; Swift, Imogen J. ; Samra, Kiran ; Shafei, Rachelle ; Timberlake, Carolyn ; Cope, Thomas ; Rittman, Timothy ; Benussi, Alberto ; Premi, Enrico ; Gasparotti, Roberto ; Archetti, Silvana ; Gazzina, Stefano ; Cantoni, Valentina ; Arighi, Andrea ; Fenoglio, Chiara ; Scarpini, Elio ; Fumagalli, Giorgio ; Borracci, Vittoria ; Rossi, Giacomina ; Giaccone, Giorgio ; Di Fede, Giuseppe ; Caroppo, Paola ; Tiraboschi, Pietro ; Prioni, Sara ; Redaelli, Veronica ; Tang-Wai, David ; Rogaeva, Ekaterina ; Castelo-Branco, Miguel ; Freedman, Morris ; Keren, Ron ; Black, Sandra ; Mitchell, Sara ; Rademakers, Rosa ; Poos, Jackie ; Papma, Janne M. ; Giannini, Lucia ; van Minkelen, Rick ; Pijnenburg, Yolande ; Nacmias, Benedetta ; Ferrari, Camilla ; Polito, Cristina ; Lombardi, Gemma ; Bessi, Valentina ; Veldsman, Michele ; Andersson, Christin ; Thonberg, Hakan ; Öijerstedt, Linn ; Jelic, Vesna ; Thompson, Paul ; Langheinrich, Tobias ; Lladó, Albert ; Antonell, Anna ; Olives, Jaume ; Balasa, Mircea ; Bargalló, Nuria ; Borrego-Ecija, Sergi ; Verdelho, Ana ; Maruta, Carolina ; Ferreira, Catarina B. ; Miltenberger-Miltenyi, Gabriel ; Simões Do Couto, Frederico ; Gabilondo, Alazne ; Gorostidi, Ana ; Villanua, Jorge ; Cañada, Marta ; Tainta, Mikel ; Zulaica, Miren ; Barandiaran, Myriam ; Alves, Patricia ; Bender, Benjamin ; Wilke, Carlo ; Graf, Lisa ; Vogels, Annick ; Vandenbulcke, Mathieu ; Van Damme, Philip ; Bruffaerts, Rose ; Poesen, Koen ; Rosa Neto, Pedro ; Gauthier, Serge ; Camuzat, Agnès ; Brice, Alexis ; Bertrand, Anne ; Funkiewiez, Aurélie ; Rinaldi, Daisy ; Saracino, Dario ; Colliot, Olivier ; Sayah, Sabrina ; Prix, Catharina ; Wlasich, Elisabeth ; Wagemann, Olivia ; Loosli, Sandra ; Schönecker, Sonja ; Hoegen, Tobias ; Lombardi, Jolina ; Anderl-Straub, Sarah ; Rollin, Adeline ; Kuchcinski, Gregory ; Bertoux, Maxime ; Lebouvier, Thibaud ; Deramecourt, Vincent ; Santiago, Beatriz ; Duro, Diana ; Leitão, Maria João ; Almeida, Maria Rosario ; Tábuas-Pereira, Miguel ; Afonso, Sónia
• Date: 2023
• Persistent ID: http://hdl.handle.net/10451/57759
• Origin: Repositório da Universidade de Lisboa
• Subject(s): Amyotrophic lateral sclerosis; Nocturnal pulsed oximetry; Phrenic nerve; Respiratory function; Respiratory tests
• Document Type: Journal article
• Language: English
• Contributor(s): Repositório Científico de Acesso Aberto da ULisboa

Description

While frontotemporal dementia has been considered a neurodegenerative disease that starts in mid-life or later, it is now clearly established that cortical and subcortical volume loss is observed more than a decade prior to symptom onset and progresses with ageing. To test the hypothesis that genetic mutations causing frontotemporal dementia have neurodevelopmental consequences, we examined the youngest adults in the GENFI cohort of pre-symptomatic frontotemporal dementia mutation carriers who are between 19 and 30 years of age. Structural brain differences and improved performance on some cognitive tests were found for MAPT and GRN mutation carriers relative to familial non-carriers, while smaller volumes were observed in C9orf72 repeat expansion carriers at a mean age of 26 years. The detection of such early differences supports potential advantageous neurodevelopmental consequences of some frontotemporal dementia-causing genetic mutations. These results have implications for the design of therapeutic interventions for frontotemporal dementia. Future studies at younger ages are needed to identify specific early pathophysiologic or compensatory processes that occur during the neurodevelopmental period.