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Research paper
Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease
  1. Julie C Stout1,
  2. Rebecca Jones2,
  3. Izelle Labuschagne1,
  4. Alison M O'Regan1,
  5. Miranda J Say3,
  6. Eve M Dumas4,
  7. Sarah Queller1,5,
  8. Damian Justo6,
  9. Rachelle Dar Santos7,
  10. Allison Coleman7,
  11. Ellen P Hart4,
  12. Alexandra Dürr6,
  13. Blair R Leavitt7,
  14. Raymund A Roos4,
  15. Doug R Langbehn8,
  16. Sarah J Tabrizi3,
  17. Chris Frost2
  1. 1School of Psychology and Psychiatry, Monash University, Melbourne, Victoria, Australia
  2. 2Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
  3. 3UCL Institute of Neurology, University College London, London, UK
  4. 4Department of Neurology, Leiden University Medical Centre, The Netherlands
  5. 5Queller Consulting, Dunedin, Florida, USA
  6. 6Department of Genetics and Cytogenetics, and INSERM UMR S679, APHP Hôpital de la Salpêtrière, Paris, France
  7. 7Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
  8. 8Departments of Psychiatry and Biostatistics (Secondary), University of Iowa, Iowa City, Iowa, USA
  1. Correspondence to Professor J C Stout, School of Psychology and Psychiatry, Monash University, Wellington Road, Melbourne, Victoria 3800, Australia; julie.stout{at}


Background Deterioration of cognitive functioning is a debilitating symptom in many neurodegenerative diseases, such as Huntington's disease (HD). To date, there are no effective treatments for the cognitive problems associated with HD. Cognitive assessment outcomes will have a central role in the efforts to develop treatments to delay onset or slow the progression of the disease. The TRACK-HD study was designed to build a rational basis for the selection of cognitive outcomes for HD clinical trials.

Methods There were a total of 349 participants, including controls (n=116), premanifest HD (n=117) and early HD (n=116). A standardised cognitive assessment battery (including nine cognitive tests comprising 12 outcome measures) was administered at baseline, and at 12 and 24 months, and consisted of a combination of paper and pencil and computerised tasks selected to be sensitive to cortical-striatal damage or HD. Each cognitive outcome was analysed separately using a generalised least squares regression model. Results are expressed as effect sizes to permit comparisons between tasks.

Results 10 of the 12 cognitive outcomes showed evidence of deterioration in the early HD group, relative to controls, over 24 months, with greatest sensitivity in Symbol Digit, Circle Tracing direct and indirect, and Stroop word reading. In contrast, there was very little evidence of deterioration in the premanifest HD group relative to controls.

Conclusions The findings describe tests that are sensitive to longitudinal cognitive change in HD and elucidate important considerations for selecting cognitive outcomes for clinical trials of compounds aimed at ameliorating cognitive decline in HD.

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  • Funding TRACK-HD is supported by the CHDI/High Q Foundation Inc, a not for profit organisation dedicated to finding treatments for Huntington's disease.

  • Competing interests None.

  • Ethics approval Ethics approval was provided by University College London, Monash University, University of British Columbia, Leiden University Medical Centre and Hôpital de la Pitié-Salpêtrière.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement TRACK-HD is not an open access study, but CHDI and the study investigators are committed to ensuring that TRACK-HD data are used to define and validate the most promising endpoints for clinical trials in Huntington's disease using the best analytical, state of the art approaches available. The study includes 36 month longitudinal 3T MRI, clinical, cognitive, quantitative motor, oculomotor and neuropsychiatric measures, and a standardised plasma collection protocol. Requests for access to unpublished data should be sent to the study coordinators (coordination{at} and will be considered by the Study Steering Committee on a case by case basis.