Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia

J.M. Poos*, L.C. Jiskoot, S.M.J. Leijdesdorff, H. Seelaar, J.L. Panman, E.L. van der Ende, M.O. Mol, L.H.H. Meeter, Y.A.L. Pijnenburg, L.D. Kaat, F.J. de Jong, J.C. van Swieten, J.M. Papma, E. van den Berg

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)1603-1612
Number of pages10
JournalJournal of Neurology
Issue number6
Publication statusPublished - 1 Jun 2020


  • AGE
  • Cognition
  • FTD
  • Frontotemporal dementia
  • GRN
  • Genetic
  • MAPT
  • Neuropsychology
  • age
  • clinical characteristics
  • cognition
  • frontotemporal dementia
  • ftd
  • genetic
  • grn
  • lobar degeneration
  • mapt
  • memory
  • neuropsychology
  • phenotype
  • progranulin mutation carriers

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