Cognitive decline in Huntington's disease expansion gene carriers

Verena Baake, Robert H.A.M. Reijntjes, Eve M. Dumas, Jennifer C. Thompson, Raymund A.C. Roos, Anna Rita Bentivoglio, Ida Biunno, Juliana Bronzova, Stephen Dunnett, Jan Frich, Joe Giuliano, Sergey Illarioshkin, Torsten Illmann, Jirí Klempír, G. Bernhard Landwehrmeyer, Jamie Levey, Tim McLean, Jørgen E. Nielsen, Markku Päivärinta, Sven PålhagenMaria Ramos-Arroyo, Sarah Tabrizi, Wim Vandenberghe, Tereza Uhrova, Tomáš Bernard, Sabrina Betz, Adrien Come, Selene Capodarca, Sébastien Charpentier Wildson, Vieira Da Silva, Martina Di Renzo, Ana Maria Finisterra, Ruth Fullam, Camille Genoves, Mette Gilling, Olivia J. Handley, Carina Hvalstedt, Kerstin Koppers, Claudia Lamanna, Matilde Laurà, Asunción Martínez Descals, Kristina Münkel, Lisanne Mütze, Martin Oehmen, Helene Padieu, Giovanna Calandra-Buonaura, Sabina Capellari, Pietro Cortelli, Roberto Poda, Cesa Scaglione, REGISTRY Investigators of the European Huntington's Disease Network6

Research output: Contribution to journalArticlepeer-review


Background: In Huntington's Disease (HD) cognitive decline can occur before unequivocal motor signs become apparent. As cognitive decline often starts early in the course of the disease and has a progressive nature over time, cognition can be regarded as a key target for symptomatic treatment. The specific progressive profile of cognitive decline over time is unknown. Objective: The aim of this study is to quantify the progression of cognitive decline across all HD stages, from pre-motormanifest to advanced HD, and to investigate if CAG length mediates cognitive decline. Methods: In the European REGISTRY study 2669 HD expansion gene carriers underwent annual cognitive assessment. General linear mixed models were used to model the cognitive decline for each cognitive task across all disease stages. Additionally, a model was developed to evaluate the cognitive decline based on CAG length and age rather than disease stage. Results: There was significant cognitive decline on all administered tasks throughout premotormanifest (close to estimated disease onset) participants and the subsequent motormanifest participants from stage 1 to stage 4. Performance on the Stroop Word and Stroop Color tests additionally declined significantly across the two pre-motormanifest groups: far and close to estimated disease onset. The evaluation of cognition performance in relation to CAG length and age revealed a more rapid cognitive decline in participants with longer CAG length than participants with shorter CAG length over time. Conclusion: Cognitive performance already shows decline in pre-motormanifest HD gene expansion carriers and gradually worsens to late stage HD. HD gene expansion carriers with certain CAG length have their own cognitive profile, i.e., longer CAG length is associated with more rapid decline.

Original languageEnglish
Pages (from-to)51-62
Number of pages12
Publication statusPublished - Oct 1 2017


  • Cognition
  • Huntington's disease
  • Longitudinal

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience


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