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Progression in prediagnostic Huntington disease
  1. Jason Rupp1,
  2. Tanya Blekher2,
  3. Jacqueline Jackson1,
  4. Xabier Beristain3,
  5. Jeanine Marshall1,
  6. Siu Hui4,
  7. Joanne Wojcieszek3,
  8. Tatiana Foroud
  1. 1Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA
  2. 2Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA
  3. 3Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA
  4. 4Department of Medicine, Division of Biostatistics, Indiana University School of Medicine, Regenstrief Institute, Indianapolis, Indiana, USA
  1. Correspondence to Dr T Foroud, Indiana University School of Medicine, 410 W 10th Street (HS 4021), Indianapolis, IN 46202-5251, USA; tforoud{at}


Objective To examine rates of decline in individuals at risk for Huntington disease (HD).

Methods 106 individuals at risk for HD completed a battery of neurocognitive, psychomotor and oculomotor tasks at two visits, approximately 2.5 years apart. Participants were classified as: (1) without the CAG expansion (normal controls, NC; n=68) or (2) with the CAG expansion (CAG+; n=38). The CAG+ group was further subdivided into those near to (near; n=19) or far from (far; n=19) their estimated age of onset. Longitudinal performance in the CAG+ group was evaluated with a repeated measures model with two main effects (time to onset, visit) and their interaction. Analysis of covariance was employed to detect differences in longitudinal performance in the three groups (NC, near and far).

Results In the CAG+, the interaction term was significant (p≤0.02) for four measures (movement time, alternate button tapping, variability of latency for a memory guided task and percentage of errors for a more complex memory guided task), suggesting the rate of decline was more rapid as subjects approached onset. Longitudinal progression in the three groups differed for several variables (p<0.05). In most, the near group had significantly faster progression than NC; however, comparisons of the NC and far groups were less consistent.

Conclusions Different patterns of progression were observed during the prediagnostic period. For some measures, CAG+ subjects closer to estimated onset showed a more rapid decline while for other measures the CAG+ group had a constant rate of decline throughout the prediagnostic period that was more rapid than in NC.

  • Genetics
  • Huntington's

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  • Funding This work was supported by NIH grants R01NS042659, R21NS060205, N01NS-3-2357, M01RR-00750 and UL1RR025761.

  • Competing interests None.

  • Ethics approval The study was approved by the local institutional review board (IUPUI IRB Study No 0109-12).

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