Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia

J Neurol. 2020 Jun;267(6):1603-1612. doi: 10.1007/s00415-020-09738-y. Epub 2020 Feb 12.

Abstract

Introduction: Trials to test disease-modifying treatments for frontotemporal dementia are eagerly awaited and sensitive instruments to assess potential treatment effects are increasingly urgent, yet lacking thus far. We aimed to identify gene-specific instruments assessing clinical onset and disease progression by comparing cognitive functioning between bvFTD patients across genetic mutations.

Methods: We examined differences in 7 cognitive domains between bvFTD patients with GRN (n = 20), MAPT (n = 29) or C9orf72 (n = 31) mutations, and non-carriers (n = 24), and described longitudinal (M = 22.6 months, SD = 16.6) data in a subsample (n = 27).

Results: Patients showed overall cognitive impairment, except memory recall, working memory and visuoconstruction. GRN patients performed lower on executive function (mean difference - 2.1; 95%CI - 4.1 to - 0.5) compared to MAPT and lower on attention compared to MAPT (mean difference - 2.5; 95%CI - 4.7 to - 0.3) and C9orf72 (mean difference - 2.4; 95%CI - 4.5 to - 0.3). Only MAPT patients were impaired on delayed recall (mean difference - 1.4; 95%CI - 2.1 to - 0.7). GRN patients declined rapidly on attention and memory, MAPT declined in confrontation naming, whereas C9orf72 patients were globally impaired but remained relatively stable over time on all cognitive domains.

Discussion: This study shows gene-specific cognitive profiles in bvFTD, which underlines the value of neuropsychological tests as outcome measures in upcoming trials for genetic bvFTD.

Keywords: Cognition; FTD; Frontotemporal dementia; Genetic; Neuropsychology.

MeSH terms

  • Aged
  • Attention / physiology*
  • C9orf72 Protein / genetics
  • Executive Function / physiology*
  • Female
  • Frontotemporal Dementia / classification
  • Frontotemporal Dementia / genetics*
  • Frontotemporal Dementia / physiopathology*
  • Humans
  • Longitudinal Studies
  • Male
  • Memory, Short-Term / physiology
  • Mental Recall / physiology*
  • Middle Aged
  • Neuropsychological Tests
  • Psychomotor Performance / physiology*
  • tau Proteins / genetics

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • MAPT protein, human
  • tau Proteins