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Updated: Jun 16, 2026
Whole-brain Segmentation and Change-point Analysis of Anatomical Brain MRI—Application in Premanifest Huntington's Disease
Published on: June 9, 2018
Onset and progression of pathologic atrophy in Huntington disease: a longitudinal MR imaging study
1Dementia Research Centre and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London, UK. hobbs@drc.ion.ucl.ac.uk
Insights
Huntington's disease (HD) shows significant caudate atrophy and global brain volume changes years before motor symptoms appear. These MRI measures can serve as early indicators of HD progression.
Area of Science:
- Neuroimaging
- Neurology
- Medical Research
Background:
- Huntington's disease (HD) is a neurodegenerative disorder.
- Longitudinal MR imaging can track disease progression before clinical symptoms manifest.
- Identifying early biomarkers is crucial for assessing disease-modifying treatments in HD.
Purpose of the Study:
- To investigate changes in caudate and global brain volumes in Huntington's disease (HD) progression.
- To determine if MR imaging measures can detect pathology in premanifest and early stages of HD.
- To establish the timeline of volumetric changes relative to motor onset in HD.
Main Methods:
- Serial volumetric MR imaging was performed on 40 HD gene-positive individuals and 19 controls over 27 months.
- Semiautomated procedures measured caudate, lateral ventricle, and total intracranial volumes (TIV).
- Linear mixed models analyzed group differences, controlling for TIV, sex, and age, in relation to motor onset.
Main Results:
- Significant differences in caudate and ventricular volumes were evident 14 and 5 years before motor onset, respectively.
- At motor onset, HD patients had smaller caudate volumes and larger ventricular volumes compared to controls.
- HD exhibited accelerated caudate atrophy (10-fold) and ventricular enlargement (4-fold), with the latter accelerating over time.
Conclusions:
- Evidence suggests accelerated global brain atrophy with disproportionate caudate involvement in HD.
- Both caudate and global brain volume measures show potential as early biomarkers for HD pathology.
- MR imaging can detect significant brain changes years prior to the onset of motor symptoms in HD.
Background And Purpose:
Longitudinal MR imaging measures provide an opportunity to track progression in HD before the emergence of clinical symptoms. This may prove useful in assessing disease-modifying treatments. We investigated how caudate and global volumes change as HD progresses from premanifest to early disease.
Materials And Methods:
Forty HD gene-positive individuals and 19 controls underwent serial volumetric MR imaging (baseline, 12 and 27 months; 2 or 3 scans per person). At baseline, 3 patients with HD were premanifest but developed overt motor features during the study, and 37 had early HD. All had dates of motor onset recorded. Caudates, lateral ventricles, and TIVs were measured using semiautomated procedures. Linear mixed models were used to investigate differences between HD and controls in relation to motor onset, controlling for TIV, sex, and age.
Results:
Extrapolating backwards in time, we found that differences in caudate and ventricular volumes between patients with HD and controls were evident 14 and 5 years, respectively, before motor onset (P < .05). At onset, caudate volume was 2.58 mL smaller than that in controls (P < .0001); ventricular volume was 9.27 mL larger (P < .0001). HD caudate atrophy rates were linear, showed low variability between subjects, and were approximately 10-fold higher than those in controls (P < .001). HD ventricular enlargement rates were variable between subjects, were approximately 4-fold higher than those in controls at onset (P < .001), and accelerated with disease duration (P = .02).
Conclusions:
We provide evidence of acceleration of global atrophy in HD with disproportionate caudate involvement. Both caudate and global measures may be of use as early markers of HD pathology.
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