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Longitudinal Diffusion Changes in Prodromal and Early HD: Evidence of White-matter Tract Deterioration

1Department of Radiology, University of Iowa, Iowa City, Iowa.
2Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, USA.
3Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
4Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA.
5Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Publication Date:
Hum Brain Mapp
Volume Number:
Issue Number:
Hum Brain Mapp. 2017 Mar;38(3):1460-77.
PubMed ID:
Huntington disease, computer-assisted, diffusion magnetic resonance imaging, diffusion tractography, disease progression, image processing, multicenter study, prodromal, white matter
Appears in Collections:
P41 EB015902/EB/NIBIB NIH HHS/United States
R01 MH074794/MH/NIMH NIH HHS/United States
U01 NS083223/NS/NINDS NIH HHS/United States
Generated Citation:
Shaffer J.J., Ghayoor A., Long J.D., Kim R.E-Y., Lourens S., O'Donnell L.J., Westin C-F., Rathi Y., Magnotta V., Paulsen J.S., Johnson H.J. Longitudinal Diffusion Changes in Prodromal and Early HD: Evidence of White-matter Tract Deterioration. Hum Brain Mapp. 2017 Mar;38(3):1460-77. PMID: 28045213. PMCID: PMC5400101.
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Huntington's disease (HD) is a genetic neurodegenerative disorder that primarily affects striatal neurons. Striatal volume loss is present years before clinical diagnosis; however, white matter degradation may also occur prior to diagnosis. Diffusion-weighted imaging (DWI) can measure microstructural changes associated with degeneration that precede macrostructural changes. DWI derived measures enhance understanding of degeneration in prodromal HD (pre-HD). METHODS: As part of the PREDICT-HD study, Nā€‰=ā€‰191 pre-HD individuals and 70 healthy controls underwent two or more (baseline and 1-5 year follow-up) DWI, with nā€‰=ā€‰649 total sessions. Images were processed using cutting-edge DWI analysis methods for large multicenter studies. Diffusion tensor imaging (DTI) metrics were computed in selected tracts connecting the primary motor, primary somato-sensory, and premotor areas of the cortex with the subcortical caudate and putamen. Pre-HD participants were divided into three CAG-Age Product (CAP) score groups reflecting clinical diagnosis probability (low, medium, or high probabilities). Baseline and longitudinal group differences were examined using linear mixed models. RESULTS: Cross-sectional and longitudinal differences in DTI measures were present in all three CAP groups compared with controls. The high CAP group was most affected. CONCLUSIONS: This is the largest longitudinal DWI study of pre-HD to date. Findings showed DTI differences, consistent with white matter degeneration, were present up to a decade before predicted HD diagnosis. Our findings indicate a unique role for disrupted connectivity between the premotor area and the putamen, which may be closely tied to the onset of motor symptoms in HD.

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