Cognitive decline in Huntington's disease expansion gene carriers

Verena Baake, Robert H.A.M. Reijntjes, Eve M. Dumas, Jennifer C. Thompson, REGISTRY Investigators of the European Huntington's Disease Network, Raymund A C Roos

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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
JournalCortex
Volume95
DOIs
Publication statusPublished - 1 Oct 2017
Externally publishedYes

Keywords

  • Cognition
  • Huntington's disease
  • Longitudinal
  • REGISTRY

Cite this

Baake, V., Reijntjes, R. H. A. M., Dumas, E. M., Thompson, J. C., REGISTRY Investigators of the European Huntington's Disease Network, & Roos, R. A. C. (2017). Cognitive decline in Huntington's disease expansion gene carriers. Cortex, 95, 51-62. https://doi.org/10.1016/j.cortex.2017.07.017
Baake, Verena ; Reijntjes, Robert H.A.M. ; Dumas, Eve M. ; Thompson, Jennifer C. ; REGISTRY Investigators of the European Huntington's Disease Network ; Roos, Raymund A C. / Cognitive decline in Huntington's disease expansion gene carriers. In: Cortex. 2017 ; Vol. 95. pp. 51-62.
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Baake, V, Reijntjes, RHAM, Dumas, EM, Thompson, JC, REGISTRY Investigators of the European Huntington's Disease Network & Roos, RAC 2017, 'Cognitive decline in Huntington's disease expansion gene carriers' Cortex, vol. 95, pp. 51-62. https://doi.org/10.1016/j.cortex.2017.07.017

Cognitive decline in Huntington's disease expansion gene carriers. / Baake, Verena; Reijntjes, Robert H.A.M.; Dumas, Eve M.; Thompson, Jennifer C.; REGISTRY Investigators of the European Huntington's Disease Network; Roos, Raymund A C.

In: Cortex, Vol. 95, 01.10.2017, p. 51-62.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Cognitive decline in Huntington's disease expansion gene carriers

AU - Baake, Verena

AU - Reijntjes, Robert H.A.M.

AU - Dumas, Eve M.

AU - Thompson, Jennifer C.

AU - Bentivoglio, Anna Rita

AU - Biunno, Ida

AU - Bronzova, Juliana

AU - Dunnett, Stephen B.

AU - Frich, Jan

AU - Giuliano, Joe

AU - Illarioshkin, Sergey

AU - Illmann, Torsten

AU - Klempír, Jirí

AU - Landwehrmeyer, G. Bernhard

AU - Levey, Jamie

AU - McLean, Tim

AU - Nielsen, Jørgen E.

AU - Päivärinta, Markku

AU - Pålhagen, Sven

AU - Ramos-Arroyo, Maria

AU - Tabrizi, Sarah J.

AU - Vandenberghe, Wim

AU - Uhrova, Tereza

AU - Bernard, Tomáš

AU - Betz, Sabrina

AU - Come, Adrien

AU - Capodarca, Selene

AU - Wildson, Sébastien Charpentier

AU - Da Silva, Vieira

AU - Di Renzo, Martina

AU - Finisterra, Ana Maria

AU - Fullam, Ruth

AU - Genoves, Camille

AU - Gilling, Mette

AU - Handley, Olivia J.

AU - Hvalstedt, Carina

AU - Koppers, Kerstin

AU - Lamanna, Claudia

AU - Laurà, Matilde

AU - Descals, Asunción Martínez

AU - Münkel, Kristina

AU - Mütze, Lisanne

AU - Oehmen, Martin

AU - Padieu, Helene

AU - Paterski, Laurent

AU - Koivisto, Susana Pro

AU - Rindal, Beate

AU - Røren, Niini

AU - Salgueiro, Ana

AU - Šašinková, Pavla

AU - Timewell, Erika

AU - Van Walsem, Marleen R.

AU - Witjes-Ané, Marie Noelle

AU - Zielonka, Eugeniusz

AU - Bonelli, Raphael M.

AU - Hecht, Karen

AU - Herranhof, Brigitte

AU - Holl, Anna

AU - Kapfhammer, Hans Peter

AU - Koppitz, Michael

AU - Lilek, Sabine

AU - Magnet, Markus

AU - Müller, Nicole

AU - Otti, Daniela

AU - Painold, Annamaria

AU - Reisinger, Karin

AU - Scheibl, Monika

AU - Schöggl, Helmut

AU - Ullah, Jasmin

AU - Braunwarth, Eva Maria

AU - Brugger, Florian

AU - Buratti, Lisa

AU - Hametner, Eva Maria

AU - Hepperger, Caroline

AU - Holas, Christiane

AU - Hotter, Anna

AU - Hussl, Anna

AU - Larcher, Barbara

AU - Mahlknecht, Philipp

AU - Müller, Christoph

AU - Pinter, Bernadette

AU - Poewe, Werner

AU - Reiter, Eva Magdalena

AU - Seppi, Klaus

AU - Sprenger, Fabienne

AU - Wenning, Gregor

AU - Ladurner, Gunther

AU - Lilek, Stefan

AU - Sinadinosa, Daniela

AU - Staffen, Wolfgang

AU - Walleczek, Anna Maria

AU - Dupuis, Michel

AU - Minet, Cécile

AU - Ribaï, Pascale

AU - Van Paemel, Dominique

AU - Verellen-Dumoulin, Christine

AU - Majerová, Veronika

AU - Roth, Jan

AU - Hartikainen, Paivi

AU - Ollokainen, Mari

AU - Santala, Maire

AU - Eklund, Pia

AU - Hiivola, Heli

AU - Hyppönen, Hannele

AU - Martikainen, Kirsti

AU - Tuuha, Katri

AU - Allain, Philippe

AU - Bonneau, Dominique

AU - Bost, Marie

AU - Gohier, Bénédicte

AU - Guérid, Marie Anne

AU - Olivier, Audrey

AU - Prouzet, Julie

AU - Prundean, Adriana

AU - Scherer-Gagou, Clarisse

AU - Verny, Christophe

AU - Babiloni, Blandine

AU - Debruxelles, Sabrina

AU - Duché, Charlotte

AU - Goizet, Cyril

AU - Jameau, Laetitia

AU - Lafoucrière, Danielle

AU - Spampinato, Umberto

AU - Couttier, Julien

AU - Debilly, Bérengère

AU - Delaigue, Christine

AU - Durif, Franck

AU - Legendre, Perrine

AU - Loiseau, Sylvie

AU - Ulla, Miguel

AU - Vidal, Tiphaine

AU - Bachoud-Lévi, Anne Catherine

AU - Badei, Farideh

AU - Boissé, Marie Françoise

AU - Boudali, Lotfi

AU - De Langavant, Laurent Cleret

AU - Lemoine, Laurie

AU - Morgado, Graca

AU - Youssov, Katia

AU - Annic, Agnès

AU - Barthélémy, Recka

AU - Bruycker, Christelle De

AU - Cabaret, Maryline

AU - Carette, Anne Sophie

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AU - Depelchin, Alizé

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AU - Godefroy, Olivier

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AU - Chabot, Christelle

AU - Delfini, Marie

AU - Eusebio, Alexandre

AU - Fluchere, Frédérique

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AU - Grosjean, Hélène

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AU - Mundler, Laura

AU - Nowak, Marielle

AU - Raseta, Rolland

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AU - Brice, Alexis

AU - Boster, Sarah

AU - Charles, Perrine

AU - Durr, Alexandra

AU - Ewenczyk, Claire

AU - Francisque, Hélène

AU - Jauffret, Céline

AU - Justo, Damian

AU - Kassar, Abdulrahman

AU - Klebe, Stephan

AU - Lesne, Fabien

AU - Milani, Paolo

AU - Monin, Marie Lorraine

AU - Roze, Emmanuel

AU - Tataru, Alina

AU - Tchikviladzé, Maya

AU - Bioux, Sandrine

AU - Bliaux, Evangeline

AU - Girard, Carole

AU - Guyant-Maréchal, Lucie

AU - Hannequin, Didier

AU - Hannier, Véronique

AU - Jourdain, Séverine

AU - Maltête, David

AU - Pouliquen, Dorothée

AU - Anheim, Mathieu

AU - Barun, Nadia

AU - Lagha-Boukbiza, Ouhaid

AU - Longato, Nadine

AU - Marcel, Christophe

AU - Phillipps, Clélie

AU - Rudolf, Gabrielle

AU - Steinmetz, Gisèle

AU - Tranchant, Christine

AU - Wagner, Caroline

AU - Zimmermann, Marie Agathe

AU - Blondeau, Leily

AU - Calvas, Fabienne

AU - Cheriet, Samia

AU - Delabaere, Helène

AU - Demonet, Jean François

AU - Pariente, Jérémie

AU - Pierre, Michèle

AU - Rolland, Sandrine

AU - Kosinski, Christoph Michael

AU - Milkereit, Eva

AU - Probst, Daniela

AU - Reetz, Kathrin

AU - Sass, Christian

AU - Schiefer, Johannes

AU - Schlangen, Christiane

AU - Werner, Cornelius J.

AU - Beuth, Markus

AU - Gelderblom, Harald

AU - Ure, Alexandra

AU - REGISTRY Investigators of the European Huntington's Disease Network

AU - Roos, Raymund A C

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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.

AB - 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.

KW - Cognition

KW - Huntington's disease

KW - Longitudinal

KW - REGISTRY

UR - http://www.scopus.com/inward/record.url?scp=85027997207&partnerID=8YFLogxK

U2 - 10.1016/j.cortex.2017.07.017

DO - 10.1016/j.cortex.2017.07.017

M3 - Article

VL - 95

SP - 51

EP - 62

JO - Cortex

JF - Cortex

SN - 0010-9452

ER -

Baake V, Reijntjes RHAM, Dumas EM, Thompson JC, REGISTRY Investigators of the European Huntington's Disease Network, Roos RAC. Cognitive decline in Huntington's disease expansion gene carriers. Cortex. 2017 Oct 1;95:51-62. https://doi.org/10.1016/j.cortex.2017.07.017