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Apathy predicts rate of cognitive decline over 24 months in premanifest Huntington's disease

Published online by Cambridge University Press:  17 February 2020

S. C. Andrews
School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, Victoria, Australia Neuroscience Research Australia, Sydney, NSW, Australia School of Psychology, University of New South Wales, Sydney, NSW, Australia
D. R. Langbehn
Department of Psychiatry, University of Iowa, Iowa City, USA
D. Craufurd
Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
A. Durr
Sorbonne Université, Institut du Cerveau et de la Moelle épinière (ICM), University Hospital Pitié-Salpêtrière, AP-HP, Inserm U 1127, CNRS UMR 7225, Paris, France
B. R. Leavitt
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada
R. A. Roos
Department Neurology LUMC, Universiteit Leiden, Leiden, The Netherlands
S. J. Tabrizi
Department of Neurodegenerative Diseases, University College London, Queen Square Institute of Neurology, and National Hospital for Neurology and Neurosurgery, London, UK
J. C. Stout*
School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, Victoria, Australia
Author for correspondence: J. C. Stout, E-mail:



Cognitive impairment is a core feature of Huntington's disease (HD), however, the onset and rate of cognitive decline is highly variable. Apathy is the most common neuropsychiatric symptom of HD, and is associated with cognitive impairment. The aim of this study was to investigate apathy as a predictor of subsequent cognitive decline over 2 years in premanifest and early HD, using a prospective, longitudinal design.


A total of 118 premanifest HD gene carriers, 111 early HD and 118 healthy control participants from the multi-centre TRACK-HD study were included. Apathy symptoms were assessed at baseline using the apathy severity rating from the Short Problem Behaviours Assessment. A composite of 12 outcome measures from nine cognitive tasks was used to assess cognitive function at baseline and after 24 months.


In the premanifest group, after controlling for age, depression and motor signs, more apathy symptoms predicted faster cognitive decline over 2 years. In contrast, in the early HD group, more motor signs, but not apathy, predicted faster subsequent cognitive decline. In the control group, only older age predicted cognitive decline.


Our findings indicate that in premanifest HD, apathy is a harbinger for cognitive decline. In contrast, after motor onset, in early diagnosed HD, motor symptom severity more strongly predicts the rate of cognitive decline.

Original Articles
Copyright © The Author(s) 2020. Published by Cambridge University Press

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TRACK-HD Investigators:

Canada – A Coleman, R Dar Santos, J Decolongon, A Sturrock (University of British Columbia, Vancouver).

France – E Bardinet, C Jauff ret, D Justo, S Lehericy, C Marelli, K Nigaud, R Valabrègue (APHP, Hôpital Salpêtriere, Paris).

Germany – N Bechtel, R Reilmann (University of Münster, Münster); A Hoff man, P Kraus (University of Bochum, Bochum); B Landwehrmeyer (University of Ulm)

Netherlands – SJA van den Bogaard, E M Dumas, J van der Grond, EP t'Hart, C Jurgens, M-N Witjes-Ane (Leiden University Medical Centre, Leiden).

UK – N Arran, J Callaghan (St Mary's Hospital, Manchester); C Frost, R Jones (London School of Hygiene and Tropical Medicine, London); N Fox, N Hobbs, N Lahiri, R Ordidge, G Owen, T Pepple, J Read, M Say, R Scahill, E Wild (University College London, London); S Keenan (Imperial College London, London); D M Cash (IXICO, London); S Hicks, C Kennard (Oxford)

USA – E Axelson, H Johnson, D Langbehn, C Wang (University of Iowa, Iowa City, IA); S Lee, W Monaco, H Rosas (Massachusetts General Hospital, Harvard, MA); C Campbell, S Queller, K Whitlock (Indiana University, IN).

Australia – C Campbell, M Campbell, E Frajman, C Milchman, A O'Regan (Monash University, Victoria).


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