Malpetti, MauraJones, P. SimonTsvetanov, Kamen A.Rittman, TimothySwieten, John C.Borroni, BarbaraSanchez‐Valle, RaquelMoreno, FerminLaforce, RobertGraff, CarolineSynofzik, MatthisGalimberti, DanielaMasellis, MarioTartaglia, Maria CarmelaFinger, ElizabethVandenberghe, RikMendonça, Alexandre deTagliavini, FabrizioSantana, IsabelDucharme, SimonButler, Chris R.Gerhard, AlexanderLevin, JohannesDanek, AdrianOtto, MarkusFrisoni, Giovanni B.Ghidoni, RobertaSorbi, SandroHeller, CarolinTodd, Emily G.Bocchetta, MartinaCash, David M.Convery, Rhian S.Peakman, GeorgiaMoore, Katrina M.Rohrer, Jonathan D.Kievit, Rogier A.Rowe, James B.GENFI - Genetic Frontotemporal dementia Initiative2020-12-172020-12-172020Alzheimer’s Dement. 2020;00-00.1552-5260http://hdl.handle.net/10451/45431© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.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.engApathyCognitive declineGenetic frontotemporal dementiaLongitudinal designMRIPresymptomatic carriersjournal article10.1002/alz.122522352-8729