Impairment of episodic memory in genetic frontotemporal dementia: A genfi study

Jackie M. Poos*, Lucy L. Russell, Georgia Peakman, Martina Bocchetta, Caroline V. Greaves, Lize C. Jiskoot, Emma L. van der Ende, Harro Seelaar, Janne M. Papma, Esther van den Berg, Yolande A.L. Pijnenburg, Barbara Borroni, Raquel Sanchez-Valle, Fermin Moreno, Robert Laforce, Caroline Graff, Matthias Synofzik, Daniela Galimberti, James B. Rowe, Mario MasellisCarmela Tartaglia, Elizabeth Finger, Rik Vandenberghe, Alexandre de Medonça, Fabrizio Tagliavini, Chris R. Butler, Isabel Santana, Isabelle Le Ber, Alex Gerhard, Simon Ducharme, Johannes Levin, Adrian Danek, Markus Otto, Sandro Sorbi, Florence Pasquier, John C. van Swieten, Jonathan D. Rohrer*, Martin N. Rossor, Nick C. Fox, Jason D. Warren, Katrina Moore, Rhian Convery, Imogen J. Swift, Rachelle Shafei, Carolin Heller, Emily Todd, Arabella Bouzigues, David Cash, Ione Woollacott, Henrik Zetterberg, Annabel Nelson, Jennifer Nicholas, Rita Guerreiro, Jose Bras, David L. Thomas, Simon Mead, Lieke Meeter, Jessica Pan-Man, Rick van Minkelen, Myriam Barandiaran, Begoña Indakoetxea, Alazne Gabilondo, Mikel Tainta, Ana Gorostidi, Miren Zulaica, Alina Díez, Jorge Vil-Lanua, Sergi Borrego-Ecija, Jaume Olives, Albert Lladó, Mircea Balasa, Anna Antonell, Nuria Bargalló, Enrico Premi, Stefano Gazzina, Roberto Gasparotti, Silvana Archetti, Sandra Black, Sara Mitchell, Ekaterina Rogaeva, Morris Freedman, Ron Keren, David Tang-Wai, Hakan Thon-Berg, Linn Öijerstedt, Christin Andersson, Vesna Jelic, Andrea Arighi, Chiara Fenoglio, Elio Scarpini, Giorgio Fumagalli, Thomas Cope, Carolyn Timberlake, Timothy Rittman, Christen Shoe-Smith, Robart Bartha, Rosa Rademakers, Carlo Wilke, Hans Otto Karnarth, Benjamin Bender, Rose Bruffaerts, Philip Vandamme, Math Ieu Vandenbulcke, Catarina B. Ferreira, Gabriel Miltenberger, Carolina Maruta Mpsych, Ana Verdelho, Sónia Afonso, Ricardo Taipa, Paola Caroppo, Giuseppe Di Fede, Giorgio Giac-Cone, Sara Prioni, Veronica Redaelli, Giacomina Rossi, Pietro Tiraboschi, Diana Duro, Maria Rosario Almeida, Miguel Castelo-Branco, Maria João Leitão, Miguel Tabuas-Pereira, Beatriz Santiago, Serge Gauthier, Pedro Rosa-Neto, Michele Velds-Man, Paul Thompson, Tobias Langheinrich, Catharina Prix, Tobias Hoegen, Elisabeth Wlasich, Sandra Loosli, Sonja Schonecker, Sarah Anderl-Straub, Jolina Lombardi, Nuria Bargalló, Alberto Benussi, Valentina Cantoni, Maxime Bertoux, Anne Bertrand, Alexis Brice, Agnès Camuzat, Olivier Colliot, Sabrina Sayah, Aurélie Funkiewiez, Daisy Rinaldi, Gemma Lombardi, Benedetta Nacmias, Dario Saracino, Valentina Bessi, Camilla Ferrari, Marta Cañada, Vincent Deramecourt, Gregory Kuchcinski, Thibaud Lebouvier, Sebastien Ourselin, Cristina Polito, Adeline Rollin

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Introduction: We aimed to assess episodic memory in genetic frontotemporal dementia (FTD) with the Free and Cued Selective Reminding Test (FCSRT). Methods: The FCSRT was administered in 417 presymptomatic and symptomatic mutation carriers (181 chromosome 9 open reading frame 72 [C9orf72], 163 progran-ulin [GRN], and 73 microtubule-associated protein tau [MAPT]) and 290 controls. Group differences and correlations with other neuropsychological tests were examined. We performed voxel-based morphometry to investigate the underlying neural substrates of the FCSRT. Results: All symptomatic mutation carrier groups and presymptomatic MAPT mutation carriers performed significantly worse on all FCSRT scores compared to controls. In the presymptomatic C9orf72 group, deficits were found on all scores except for the delayed total recall task, while no deficits were found in presymptomatic GRN mutation carriers. Performance on the FCSRT correlated with executive function, particularly in C9orf72 mutation carriers, but also with memory and naming tasks in the MAPT group. FCSRT performance also correlated with gray matter volumes of frontal, temporal, and subcortical regions in C9orf72 and GRN, but mainly temporal areas in MAPT mutation carriers. Discussion: The FCSRT detects presymptomatic deficits in C9orf72-and MAPT-associated FTD and provides important insight into the underlying cause of memory impairment in different forms of FTD.

Original languageEnglish
Article numbere12185
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume13
Issue number1
Early online date13 May 2021
DOIs
Publication statusPublished - 2021

Bibliographical note

Funding Information:
The Dementia Research Centre is supported by Alzheimer’s Research UK, Alzheimer’s Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society, and Alzheimer’s Research UK. J. D. Rohrer is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1); the Bluefield Project; the JPND GENFI-PROX grant (2019-02248); the Dioraphte Foundation (grant numbers 09-02-00); the Association for Frontotemporal Dementias Research Grant 2009; The Netherlands Organization for Scientific Research (NWO; grant HCMI 056-13-018); ZonMw Memorabel (Deltaplan Dementie, project numbers 733 050 103 and 733 050 813); JPND PreFrontAls consortium (project number 733051042). J. M. Poos is supported by a Fellowship award from Alzheimer Nederland (WE.15-2019.02). This work was conducted using the MRC Dementias Platform UK (MR/L023784/1 and MR/009076/1). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510.

Publisher Copyright:
© 2021 The Authors.

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