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Research paper
Cognitive impairment in the preclinical stage of dementia in FTD-3 CHMP2B mutation carriers: a longitudinal prospective study
  1. Jette Stokholm1,
  2. Thomas W Teasdale2,
  3. Peter Johannsen1,
  4. Jorgen E Nielsen1,3,
  5. Troels Tolstrup Nielsen1,3,
  6. Adrian Isaacs4,
  7. Jerry M Brown5,
  8. Anders Gade2,
  9. and the Frontotemporal dementia Research in Jutland Association (FReJA) consortium
  1. 1Memory Disorders Research Group, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  2. 2Department of Psychology, University of Copenhagen, Copenhagen, Denmark
  3. 3Section of Neurogenetics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
  4. 4Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
  5. 5Department of Neurology, Addenbrooke's Hospital, Cambridge, UK
  1. Correspondence to Jette Stokholm, Memory Disorders Research Group, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, N6702, 9 Blegdamsvej, Copenhagen 2100, Denmark; jette.stokholm{at}


Objective and methods A longitudinal study spanning over 8 years and including 17 asymptomatic individuals with CHMP2B mutations was conducted to assess the earliest neuropsychological changes in autosomal dominant neurodegenerative disease frontotemporal dementia (FTD) linked to chromosome 3 (FTD-3). Subjects were assessed with neuropsychological tests in 2002, 2005 and 2010.

Results Cross-sectional analyses showed that the mutation carriers scored lower on tests of psychomotor speed, working memory, executive functions and verbal memory than a control group consisting of not-at-risk family members and spouses. Longitudinal analyses showed a gradual decline in psychomotor speed, working memory capacity and global executive measures in the group of non-demented mutation carriers that was not found in the control group. In contrast, there were no significant group differences in domain scores on memory or visuospatial functions. On an individual level the cognitive changes over time varied considerably.

Conclusion Subjects with CHMP2B mutation show cognitive changes dominated by executive dysfunctions, years before they fulfil diagnostic criteria of FTD. However, there is great heterogeneity in the individual cognitive trajectories.

  • Neuropsychology
  • Dementia
  • Genetics

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