title: Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease.
abstract: 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.
authors.affiliation: School of Psychology and Psychiatry, Monash University, Melbourne, Victoria, Australia. julie.stout@monash.edu
authors.forename: Julie C
authors.initials: JC
authors.lastname: Stout
authors.forename: Rebecca
authors.initials: R
authors.lastname: Jones
authors.forename: Izelle
authors.initials: I
authors.lastname: Labuschagne
authors.forename: Alison M
authors.initials: AM
authors.lastname: O'Regan
authors.forename: Miranda J
authors.initials: MJ
authors.lastname: Say
authors.forename: Eve M
authors.initials: EM
authors.lastname: Dumas
authors.forename: Sarah
authors.initials: S
authors.lastname: Queller
authors.forename: Damian
authors.initials: D
authors.lastname: Justo
authors.forename: Rachelle Dar
authors.initials: RD
authors.lastname: Santos
authors.forename: Allison
authors.initials: A
authors.lastname: Coleman
authors.forename: Ellen P
authors.initials: EP
authors.lastname: Hart
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dürr
authors.forename: Blair R
authors.initials: BR
authors.lastname: Leavitt
authors.forename: Raymund A
authors.initials: RA
authors.lastname: Roos
authors.forename: Doug R
authors.initials: DR
authors.lastname: Langbehn
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
authors.forename: Chris
authors.initials: C
authors.lastname: Frost
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D003072:Cognition Disorders / Q000209:etiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D012737:Sex Factors; D013997:Time Factors; D055815:Young Adult