Neurodevelopmental effects of genetic frontotemporal dementia in young adult mutation carriers
Authors: 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 ,   the Genetic FTD Initiative, GENFI, 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 Gabriel , do Couto Frederico Simões , 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 
Published: November 2022

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.