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

on behalf of the Genetic FTD Initiative (GENFI), 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 SantanaSimon 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, Rogier A. Kievit

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalAlzheimer's and Dementia
Publication statusAccepted/In press - 2020


  • apathy
  • cognitive decline
  • genetic frontotemporal dementia
  • longitudinal design
  • MRI
  • presymptomatic carriers

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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