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F44 Disentangling apathy subtypes in huntington’s disease: a white matter biomarker of disease profile and progression
  1. Audrey E De Paepe1,
  2. Joanna Sierpowska2,3,
  3. Clara García-Gorro2,4,
  4. Saül Martinez-Horta5,6,
  5. Jesus Perez-Perez5,6,
  6. Jaime Kulisevsky5,6,7,
  7. Nadia Rodriguez-Dechicha8,
  8. Irene Vaquer8,
  9. Susana Subira8,9,
  10. Matilde Calopa10,
  11. Esteban Muñoz11,12,13,
  12. Pilar Santacruz11,
  13. Jesus Ruiz-Idiago14,
  14. Celia Mareca14,
  15. Ruth de Diego-Balaguer2,4,15,16,
  16. Estela Camara2
  1. 1Pomona College, Claremont,USA
  2. 2Cognition and Brain Plasticity Unit, IDIBELL (Institut d’Investigació Biomèdica de Bellvitge), L’Hospitalet de Llobregat (Barcelona), Spain
  3. 3Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
  4. 4Department of Cognition, Development and Educational Psychology, University of Barcelona, Barcelona, Spain
  5. 5Movement Disorders Unit, Department of Neurology, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  6. 6CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases), Carlos III Institute, Madrid, Spain
  7. 7Universidad Autónoma de Barcelona, Barcelona, Spain
  8. 8Hestia Duran i Reynals. Hospital Duran i Reynals, Hospitalet de Llobregat (Barcelona), Spain
  9. 9Department of Clinical and Health Psychology, Universitat Autònoma de Barcelona, Barcelona, Spain
  10. 10Movement Disorders Unit, Neurology Service, Hospital Universitari de Bellvitge, Barcelona, Spain
  11. 11Movement Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain
  12. 12IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
  13. 13Facultat de Medicina, University of Barcelona, Barcelona, Spain
  14. 14Hospital Mare de Deu de la Mercè, Barcelona, Spain
  15. 15The Institute of Neurosciences, University of Barcelona, Barcelona, Spain
  16. 16ICREA (Catalan Institute for Research and Advanced Studies), Barcelona, Spain


Along with motor and cognitive deterioration, neuropsychiatric symptoms form a common feature of Huntington’s disease. Of these, apathy has been shown to most highly correlate with disease progression, often emerging prior to clinical diagnosis. However, due to the multidimensional nature of apathy, its elusive etiology, and the lack of operative diagnostic criteria, treatment options are limited. The present study combine diffusion tensor imaging (DTI) with precise apathy scales to investigate the relationship between white matter microstructural change and apathy in premanifest (n=22) and early manifest Huntington’s disease (n=24) compared with controls (n=35).Global apathy was measured using both the short Problem Behavior Assessment and the Lille Apathy Rating Scale, short-form. Principle component analysis of the LARS-s produced three apathy subtypes: emotional, cognitive, and auto-activation deficit. We found that premanifest participant’s portrayed significantly higher auto-activation deficit apathy, with early manifest patients additionally showing significantly increased apathy in cognitive apathy as well as global apathy. Analysis by DTI showed a significant rightward disturbance in the uncinate fasciculus (UF), the frontostriatal tract (FST), and the dorsolateral prefrontal cortex to caudate nucleus tract (dlPFC-cn). Importantly, specific apathy subtypes were found to be associated with discrete tracts. Specifically, higher levels of subtype-specific apathy correlated with a lateralized decrease in structural connectivity in the dlPFC-cn and FST for the cognitive domain of apathy and in the UF for auto-activation deficit, predominantly on the right side. That apathy subtypes are associated with distinct white matter substrates supports the importance of an individualized approach to its diagnosis and treatment.

  • apathy
  • Huntington’s disease
  • neurodegeneration
  • tractography.

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