Detection of Huntington's disease decades before diagnosis: the Predict-HD study

J Neurol Neurosurg Psychiatry. 2008 Aug;79(8):874-80. doi: 10.1136/jnnp.2007.128728. Epub 2007 Dec 20.


Objective: The objective of the Predict-HD study is to use genetic, neurobiological and refined clinical markers to understand the early progression of Huntington's disease (HD), prior to the point of traditional diagnosis, in persons with a known gene mutation. Here we estimate the approximate onset and initial course of various measurable aspects of HD relative to the time of eventual diagnosis.

Methods: We studied 438 participants who were positive for the HD gene mutation, but did not yet meet the diagnostic criteria for HD and had no functional decline. Predictability of baseline cognitive, motor, psychiatric and imaging measures was modelled non-linearly using estimated time until diagnosis (based on CAG repeat length and current age) as the predictor.

Results: Estimated time to diagnosis was related to most clinical and neuroimaging markers. The patterns of association suggested the commencement of detectable changes one to two decades prior to the predicted time of clinical diagnosis. The patterns were highly robust and consistent, despite the varied types of markers and diverse measurement methodologies.

Conclusions: These findings from the Predict-HD study suggest the approximate time scale of measurable disease development, and suggest candidate disease markers for use in preventive HD trials.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Attention
  • Caudate Nucleus / pathology
  • Chromosomes, Human, Pair 4 / genetics
  • Early Diagnosis
  • Female
  • Genetic Testing*
  • Humans
  • Huntingtin Protein
  • Huntington Disease / diagnosis*
  • Huntington Disease / genetics
  • Longitudinal Studies
  • Magnetic Resonance Imaging*
  • Male
  • Mental Recall
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Neurologic Examination*
  • Neuropsychological Tests*
  • Nuclear Proteins / genetics*
  • Olfaction Disorders / diagnosis
  • Olfaction Disorders / genetics
  • Predictive Value of Tests
  • Probability
  • Putamen / pathology
  • Reaction Time
  • Trinucleotide Repeats
  • Verbal Learning


  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins