Apathy in presymptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes

Malpetti, Maura; Jones, P Simon; Tsvetanov, Kamen A; Rittman, Timothy; van Swieten, John C; Borroni, Barbara; Sanchez-Valle, Raquel; Moreno, Fermin; Laforce, Robert; Graff, Caroline; Synofzik, Matthis; Galimberti, Daniela; Masellis, Mario; Tartaglia, Maria Carmela; Finger, Elizabeth; Vandenberghe, Rik; de Mendonça, Alexandre; Tagliavini, Fabrizio; Santana, Isabel; Ducharme, Simon; Butler, Chris R; Gerhard, Alexander; Levin, Johannes; Danek, Adrian; Otto, Markus; Frisoni, Giovanni B; Ghidoni, Roberta; Sorbi, Sandro; Heller, Carolin; Todd, Emily G; Bocchetta, Martina; Cash, David M; Convery, Rhian S; Peakman, Georgia; Moore, Katrina M; Rohrer, Jonathan D; Kievit, Rogier A; Rowe, James B; Afonso, Sónia; Maria Rosario Almeida,; Anderl-Straub, Sarah; Andersson, Christin; Antonell, Anna; Archetti, Silvana; Arighi, Andrea; Balasa, Mircea; Barandiaran, Myriam; Bargalló, Nuria; Bartha, Robart; Bender, Benjamin; Benussi, Alberto; Benussi, Luisa; Bessi, Valentina; Binetti, Giuliano; Black, Sandra; Borrego-Ecija, Sergi; Bras, Jose; Bruffaerts, Rose; Cañada, Marta; Caroppo, Paola; Castelo-Branco, Miguel; Cope, Thomas; Cosseddu, Maura; Giuseppe Di Fede,; Díez, Alina; Duro, Diana; Fenoglio, Chiara; Ferrari, Camilla; Catarina, B Ferreira; Fox, Nick; Freedman, Morris; Fumagalli, Giorgio; Gabilondo, Alazne; Gasparotti, Roberto; Gauthier, Serge; Gazzina, Stefano; Giaccone, Giorgio; Gorostidi, Ana; Greaves, Caroline; Guerreiro, Rita; Hoegen, Tobias; Indakoetxea, Begoña; Jelic, Vesna; Jiskoot, Lize; Karnath, Hans-Otto; Keren, Ron; Langheinrich, Tobias; Maria João Leitão,; Lladó, Albert; Lombardi, Gemma; Loosli, Sandra; Maruta, Carolina; Mead, Simon; Meeter, Lieke; Miltenberger, Gabriel; Rick van Minkelen,; Mitchell, Sara; Nacmias, Benedetta; Nicholas, Jennifer; Öijerstedt, Linn; Olives, Jaume; Ourselin, Sebastien; Padovani, Alessandro; Panman, Jessica; Papma, Janne; Pievani, Michela; Pijnenburg, Yolande; Polito, Cristina; Premi, Enrico; Prioni, Sara; Prix, Catharina; Rademakers, Rosa; Redaelli, Veronica; Rogaeva, Ekaterina; Rosa-Neto, Pedro; Rossi, Giacomina; Rosser, Martin; Santiago, Beatriz; Scarpini, Elio; Schönecker, Sonja; Semler, Elisa; Shafei, Rachelle; Shoesmith, Christen; Tábuas-Pereira, Miguel; Tainta, Mikel; Taipa, Ricardo; Tang-Wai, David; David, L Thomas; Thompson, Paul; Thonberg, Hakan; Timberlake, Carolyn; Tiraboschi, Pietro; Philip Van Damme,; Vandenbulcke, Mathieu; Veldsman, Michele; Verdelho, Ana; Villanua, Jorge; Warren, Jason; Wilke, Carlo; Woollacott, Ione; Wlasich, Elisabeth; Zetterberg, Henrik; Zulaica, Miren

doi:10.1002/alz.12252

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, 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, 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; Afonso, Sónia; Rosario Almeida, Maria; Anderl-Straub, Sarah; Andersson, Christin; Antonell, Anna; Archetti, Silvana; Arighi, Andrea; Balasa, Mircea; Barandiaran, Myriam; Bargalló, Nuria; Bartha, Robart; Bender, Benjamin; Benussi, Alberto; Benussi, Luisa; Bessi, Valentina; Binetti, Giuliano; Black, Sandra; Borrego-Ecija, Sergi; Bras, Jose; Bruffaerts, Rose; Cañada, Marta; Caroppo, Paola; Castelo-Branco, Miguel; Cope, Thomas; Cosseddu, Maura; Di Fede, Giuseppe; Díez, Alina; Duro, Diana; Fenoglio, Chiara; Ferrari, Camilla; B Ferreira, Catarina; Fox, Nick; Freedman, Morris; Fumagalli, Giorgio; Gabilondo, Alazne; Gasparotti, Roberto; Gauthier, Serge; Gazzina, Stefano; Giaccone, Giorgio; Gorostidi, Ana; Greaves, Caroline; Guerreiro, Rita; Hoegen, Tobias; Indakoetxea, Begoña; Jelic, Vesna; Jiskoot, Lize; Karnath, Hans-Otto; Keren, Ron; Langheinrich, Tobias; João Leitão, Maria; Lladó, Albert; Lombardi, Gemma; Loosli, Sandra; Maruta, Carolina; Mead, Simon; Meeter, Lieke; Miltenberger, Gabriel; van Minkelen, Rick; Mitchell, Sara; Nacmias, Benedetta; Nicholas, Jennifer; Öijerstedt, Linn; Olives, Jaume; Ourselin, Sebastien; Padovani, Alessandro; Panman, Jessica; Papma, Janne; Pievani, Michela; Pijnenburg, Yolande; Polito, Cristina; Premi, Enrico; Prioni, Sara; Prix, Catharina; Rademakers, Rosa; Redaelli, Veronica; Rogaeva, Ekaterina; Rosa-Neto, Pedro; Rossi, Giacomina; Rosser, Martin; Santiago, Beatriz; Scarpini, Elio; Schönecker, Sonja; Semler, Elisa; Shafei, Rachelle; Shoesmith, Christen; Tábuas-Pereira, Miguel; Tainta, Mikel; Taipa, Ricardo; Tang-Wai, David; L Thomas, David; Thompson, Paul; Thonberg, Hakan; Timberlake, Carolyn; Tiraboschi, Pietro; Van Damme, Philip; Vandenbulcke, Mathieu; Veldsman, Michele; Verdelho, Ana; Villanua, Jorge; Warren, Jason; Wilke, Carlo; Woollacott, Ione; Wlasich, Elisabeth; Zetterberg, Henrik; Zulaica, Miren. - In: ALZHEIMER'S & DEMENTIA. - ISSN 1552-5260. - 17:6(2021), pp. 969-983. [10.1002/alz.12252]