Introduction: Apathy adversely affects prognosis and survival of patients with frontotemporal dementia (FTD). We test whether apathy develops in presymptomatic genetic FTD, and is associated with cognitive decline and brain atrophy. Methods: Presymptomatic carriers of MAPT, GRN or C9orf72 mutations (N = 304), and relatives without mutations (N = 296) underwent clinical assessments and MRI at baseline, and annually for 2 years. Longitudinal changes in apathy, cognition, gray matter volumes, and their relationships were analyzed with latent growth curve modeling. Results: Apathy severity increased over time in presymptomatic carriers, but not in non-carriers. In presymptomatic carriers, baseline apathy predicted cognitive decline over two years, but not vice versa. Apathy progression was associated with baseline low gray matter volume in frontal and cingulate regions. Discussion: Apathy is an early marker of FTD-related changes and predicts a subsequent subclinical deterioration of cognition before dementia onset. Apathy may be a modifiable factor in those at risk of FTD.
Apathy in presymptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes / Maura Malpetti; P. Simon Jones; Kamen A. Tsvetanov; Timothy Rittman; John C. 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 Mendon??a; Fabrizio Tagliavini; Isabel Santana; Simon Ducharme; Chris R. Butler; Alexander Gerhard; Johannes Levin; Adrian Danek; Markus Otto; Giovanni B. Frisoni; Roberta Ghidoni; Sandro Sorbi; Carolin Heller; Emily G. Todd; Martina Bocchetta; David M. Cash; Rhian S. Convery; Georgia Peakman; Katrina M. Moore; Jonathan D. Rohrer; Rogier A. Kievit; James B. Rowe; Genetic FTD Initiative (GENFI): 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, Alberto Benussi, Luisa Benussi, Valentina Bessi, Giuliano Binetti, Sandra Black, Sergi Borrego-Ecija, Jose Bras, Rose Bruffaerts, Marta Cañada, Paola Caroppo, Miguel Castelo-Branco, Thomas Cope, Maura Cosseddu, Giuseppe Di Fede, Alina Díez, Diana Duro, Chiara Fenoglio, Camilla Ferrari, Catarina B Ferreira, Nick Fox, Morris Freedman, Giorgio Fumagalli, Alazne Gabilondo, Roberto Gasparotti, Serge Gauthier, Stefano Gazzina, Giorgio Giaccone, Ana Gorostidi, Caroline Greaves, Rita Guerreiro, Tobias Hoegen, Begoña Indakoetxea, Vesna Jelic, Lize Jiskoot, Hans-Otto Karnath, Ron Keren, Tobias Langheinrich, Maria João Leitão, Albert Lladó, Gemma Lombardi, Sandra Loosli, Carolina Maruta, Simon Mead, Lieke Meeter, Gabriel Miltenberger, Rick van Minkelen, Sara Mitchell, Benedetta Nacmias, Jennifer Nicholas, Linn Öijerstedt, Jaume Olives, Sebastien Ourselin, Alessandro Padovani, Jessica Panman, Janne Papma, Michela Pievani, Yolande Pijnenburg, Cristina Polito, Enrico Premi, Sara Prioni, Catharina Prix, Rosa Rademakers, Veronica Redaelli, Ekaterina Rogaeva, Pedro Rosa-Neto, Giacomina Rossi, Martin Rosser, Beatriz Santiago, Elio Scarpini, Sonja Schönecker, Elisa Semler, Rachelle Shafei, Christen Shoesmith, Miguel Tábuas-Pereira, Mikel Tainta, Ricardo Taipa, David Tang-Wai, David L Thomas, Paul Thompson, Hakan Thonberg, Carolyn Timberlake, Pietro Tiraboschi, Philip Van Damme, Mathieu Vandenbulcke, Michele Veldsman, Ana Verdelho, Jorge Villanua, Jason Warren, Carlo Wilke, Ione Woollacott, Elisabeth Wlasich, Henrik Zetterberg, Miren Zulaica. - In: ALZHEIMER'S & DEMENTIA. - ISSN 1552-5279. - ELETTRONICO. - 17:(2020), pp. 969-983. [10.1002/alz.12252]
Apathy in presymptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes
Sandro Sorbi;Valentina Bessi;Camilla Ferrari;Gemma Lombardi;Benedetta Nacmias;
2020
Abstract
Introduction: Apathy adversely affects prognosis and survival of patients with frontotemporal dementia (FTD). We test whether apathy develops in presymptomatic genetic FTD, and is associated with cognitive decline and brain atrophy. Methods: Presymptomatic carriers of MAPT, GRN or C9orf72 mutations (N = 304), and relatives without mutations (N = 296) underwent clinical assessments and MRI at baseline, and annually for 2 years. Longitudinal changes in apathy, cognition, gray matter volumes, and their relationships were analyzed with latent growth curve modeling. Results: Apathy severity increased over time in presymptomatic carriers, but not in non-carriers. In presymptomatic carriers, baseline apathy predicted cognitive decline over two years, but not vice versa. Apathy progression was associated with baseline low gray matter volume in frontal and cingulate regions. Discussion: Apathy is an early marker of FTD-related changes and predicts a subsequent subclinical deterioration of cognition before dementia onset. Apathy may be a modifiable factor in those at risk of FTD.
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