en
Scientific article
Open access
English

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

Published inAlzheimer's & dementia, vol. 17, no. 6, p. 969-983
Publication date2021-06
First online date2020-12-14
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.

eng
Keywords
  • MRI
  • Apathy
  • Cognitive decline
  • Genetic frontotemporal dementia
  • Longitudinal design
  • Presymptomatic carriers
  • Atrophy / pathology
  • Brain / pathology
  • Cognitive Dysfunction / pathology
  • Female
  • Frontotemporal Dementia / genetics
  • Gray Matter / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation / genetics
  • Prodromal Symptoms
Funding
  • Medical Research Council - [MC_UU_00005/12]
  • Medical Research Council - [MR/M008525/1]
  • Medical Research Council - [MR/M023664/1]
  • Medical Research Council - [MR/T046015/1]
  • Medical Research Council - [MR/M009041/1]
  • Medical Research Council - [MR/J009482/1]
  • Medical Research Council - [MR/K010395/1]
  • Medical Research Council - [MC_U105597119]
  • Wellcome Trust - Restoring brain function: from cortical microcircuits to complex behaviours in neurodegenerative disease. [103838]
Citation (ISO format)
MALPETTI, Maura et al. Apathy in presymptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes. In: Alzheimer’s & dementia, 2021, vol. 17, n° 6, p. 969–983. doi: 10.1002/alz.12252
Main files (1)
Article (Published version)
Secondary files (1)
Identifiers
ISSN of the journal1552-5260
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