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Cortex. 2017 Oct;95:51-62. doi: 10.1016/j.cortex.2017.07.017. Epub 2017 Aug 3.

Cognitive decline in Huntington's disease expansion gene carriers.

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Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands; Topaz, Leiden, The Netherlands. Electronic address:
Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands.
Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands; Tjongerschans Hospital, Heerenveen, The Netherlands.
Manchester Academic Health Sciences Centre, Cerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom; Faculty of Biology, Medicine and Health, Division of Neuroscience and Experimental Psychology, University of Manchester, Manchester, United Kingdom.



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.


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.


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.


There was significant cognitive decline on all administered tasks throughout pre-motormanifest (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.


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.


Cognition; Huntington's disease; Longitudinal; REGISTRY

[Indexed for MEDLINE]

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