Neurocognitive Signs in Prodromal Huntington Disease

Academic Article


  • Objective: PREDICT-HD is a large-scale international study of people with the Huntington disease (HD) CAG-repeat expansion who are not yet diagnosed with HD. The objective of this study was to determine the stage in the HD prodrome at which cognitive differences from CAG-normal controls can be reliably detected. Method: For each of 738 HD CAG-expanded participants, we computed estimated years to clinical diagnosis and probability of diagnosis in 5 years based on age and CAG-repeat expansion number (Langbehn, Brinkman, Falush, Paulsen, & Hayden, 2004). We then stratified the sample into groups: NEAR, estimated to be ≤9 years; MID, between 9 and 15 years; and FAR, ≥15 years. The control sample included 168 CAG-normal participants. Nineteen cognitive tasks were used to assess attention, working memory, psychomotor functions, episodic memory, language, recognition of facial emotion, sensory-perceptual functions, and executive functions. Results: Compared with the controls, the NEAR group showed significantly poorer performance on nearly all of the cognitive tests and the MID group on about half of the cognitive tests (p = .05, Cohen's d NEAR as large as -1.17, MID as large as -0.61). One test even revealed significantly poorer performance in the FAR group (Cohen's d = -0.26). Individual tasks accounted for 0.2% to 9.7% of the variance in estimated proximity to diagnosis. Overall, the cognitive battery accounted for 34% of the variance; in comparison, the Unified Huntington's Disease Rating Scale motor score accounted for 11.7%. Conclusions: Neurocognitive tests are robust clinical indicators of the disease process prior to reaching criteria for motor diagnosis of HD. © 2010 American Psychological Association.
  • Authors

    Published In

  • Neuropsychology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Stout JC; Paulsen JS; Queller S; Solomon AC; Whitlock KB; Campbell JC; Carlozzi N; Duff K; Beglinger LJ; Langbehn DR
  • Start Page

  • 1
  • End Page

  • 14
  • Volume

  • 25
  • Issue

  • 1