en
Scientific article
Open access
English

Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia

Published inAlzheimer's & dementia, vol. 17, no. 3, p. 500-514
Publication date2021-03
First online date2020-11-20
Abstract

Introduction: The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial frontotemporal dementia (FTD).

Methods: We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset.

Results: There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviorally relevant structural and functional network differences. Structure-function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non-carriers, and increased with proximity to the expected onset of disease.

Discussion: Our findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance.

eng
Keywords
  • Frontotemporal dementia (FTD)
  • Functional magnetic resonance imaging (fMRI)
  • Network connectivity
  • Presymptomatic
  • Atrophy / pathology
  • Brain / pathology
  • C9orf72 Protein / genetics
  • Cognition / physiology
  • Frontotemporal Dementia / genetics
  • Humans
  • Internationality
  • Magnetic Resonance Imaging
  • Middle Aged
  • Mutation / genetics
  • Prodromal Symptoms
  • Tau Proteins / genetics
Funding
  • Medical Research Council - [MC_UU_00005/12]
  • Medical Research Council - [MC_UU_00024/1]
  • Medical Research Council - [MR/M008525/1]
  • Medical Research Council - [MR/M023664/1]
  • Medical Research Council - [MR/T046015/1]
  • Wellcome Trust - [103838]
  • Medical Research Council - [MR/J009482/1]
  • Medical Research Council - [MC_U105597119]
  • National Institute for Health Research (NIHR) - [CL-2018-14-007]
  • ZonMw - [733050103]
  • Wellcome Trust - Restoring brain function: from cortical microcircuits to complex behaviours in neurodegenerative disease. [103838]
Citation (ISO format)
TSVETANOV, Kamen A et al. Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia. In: Alzheimer’s & dementia, 2021, vol. 17, n° 3, p. 500–514. doi: 10.1002/alz.12209
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal1552-5260
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