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Neuroimage Clin. 2018 Mar 27;19:66-70. doi: 10.1016/j.nicl.2018.03.033. eCollection 2018.

Apathy and atrophy of subcortical brain structures in Huntington's disease: A two-year follow-up study.

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Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands; Huntington Center Topaz Overduin, Katwijk, The Netherlands. Electronic address:
Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands.
Leiden University Medical Center, Department of Psychiatry, Leiden, The Netherlands; Mental Health Care of Center Delfland, Delft, The Netherlands.
Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands; Tongerschans General Hospital, Heerenveen, The Netherlands.
Huntington's Disease Centre, UCL Institute of Neurology, University College London, UK.
Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
ICM - Institut du Cerveau et de la Moelle Epinière, INSERM U1127, CNRS UMR7225, Sorbonne Universités - UPMC Université Paris VI UMR_S1127and APHP, Genetic Department, Pitié-Salpêtrière University Hospital, Paris, France.
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 M13 9PL, UK; Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Oxford Road, Manchester M13 9WL, UK.



Huntington's disease (HD) is characterized by motor and behavioral symptoms, and cognitive decline. HD gene carriers and their caregivers report the behavioral and cognitive symptoms as the most burdensome. Apathy is the most common behavioral symptom of HD and is related to clinical measures of disease progression, like functional capacity. However, it is unknown whether apathy is directly related to the neurodegenerative processes in HD.


The aim is to investigate whether an association between atrophy of subcortical structures and apathy is present in HD, at baseline and after 2 years follow-up.


Volumes of 7 subcortical structures were measured using structural T1 MRI in 171 HD gene carriers of the TRACK-HD study and apathy was assessed with the Problem Behaviors Assessment-Short, at baseline and follow-up visit. At baseline, logistic regression was used to evaluate whether volumes of subcortical brain structures were associated with the presence of apathy. Linear regression was used to assess whether subcortical atrophy was associated with the degree of apathy at baseline and with an increase in severity of apathy over time.


At baseline, smaller volume of the thalamus showed a higher probability of the presence of apathy in HD gene carriers, but none of the subcortical structures was associated with the degree of apathy. Over time, no association between atrophy of any subcortical structures and change in degree of apathy was found.


The presence of apathy is associated with atrophy of the thalamus in HD, suggesting that apathy has an underlying neural cause and might explain the high incidence of apathy in HD. However, no association was found between atrophy of these subcortical structures and increase in severity of apathy over a 2-year time period.


Apathy; Huntington's disease; Subcortical structures; Thalamus

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