Striatal volume contributes to the prediction of onset of Huntington disease in incident cases

Elizabeth H Aylward, Dawei Liu, Peggy C Nopoulos, Christopher A Ross, Ronald K Pierson, James A Mills, Jeffrey D Long, Jane S Paulsen, PREDICT-HD Investigators And Coordinators Of The Huntington Study Group, Zosia Miedzybrodzka

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Abstract

Background
Previous neuroimaging research indicates that brain atrophy in Huntington disease (HD) begins many years before movement abnormalities become severe enough to warrant diagnosis. Most clinical trials being planned for individuals in the prediagnostic stage of HD propose to use delay of disease onset as the primary outcome measure. Although formulas have been developed based on age and CAG repeat length, to predict when HD motor onset will occur, it would be useful to have additional measures that can improve the accuracy of prediction of disease onset.

Methods
The current study examined magnetic resonance imaging (MRI) measures of striatum and white matter volume in 85 individuals prospectively followed from pre-HD stage through diagnosable motor onset (incident cases) and 85 individuals individually matched with incident cases on CAG repeat length, sex, and age, who were not diagnosed with HD during the course of the study.

Results
Volumes of striatum and white matter were significantly smaller in individuals who would be diagnosed 1 to 4 years following the initial MRI scan, compared with those who would remain in the pre-HD stage. Putamen volume was the measure that best distinguished between the two groups.

Conclusions
Results suggest that MRI volumetric measures may be helpful in selecting individuals for future clinical trials in pre-HD where HD motor onset is the primary outcome measure. In planning for multisite clinical trials in pre-HD, investigators may also want to consider using more objective measures, such as MRI volumes, in addition to onset of diagnosable movement disorder, as major outcome measures.
Original languageEnglish
Pages (from-to)822-828
Number of pages7
JournalBiological Psychiatry
Volume71
Issue number9
DOIs
Publication statusPublished - 1 May 2012

Keywords

  • Huntington disease
  • MRI
  • onset
  • prediction
  • prospective
  • striatum

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    Aylward, E. H., Liu, D., Nopoulos, P. C., Ross, C. A., Pierson, R. K., Mills, J. A., Long, J. D., Paulsen, J. S., PREDICT-HD Investigators And Coordinators Of The Huntington Study Group, & Miedzybrodzka, Z. (2012). Striatal volume contributes to the prediction of onset of Huntington disease in incident cases. Biological Psychiatry, 71(9), 822-828. https://doi.org/10.1016/j.biopsych.2011.07.030