Progression of structural neuropathology in preclinical Huntington's disease: a tensor based morphometry study

Area of Science:

• Neuroimaging
• Neurology
• Genetics

Background:

• Regional cerebral atrophy is present in Huntington's disease (HD) gene mutation carriers before clinical diagnosis.
• Measuring preclinical HD pathology progression is crucial for developing therapies to delay symptom onset.
• Current methods struggle to reliably track disease progression in the preclinical phase of HD.

Purpose of the Study:

• To test the hypothesis that longitudinal statistical imaging can detect structural pathology progression in preclinical HD gene mutation carriers.
• To identify if imaging can show disease progression in the absence of measurable clinical changes.

Main Methods:

• Serial clinical and MRI assessments were conducted over 2 years in 30 subjects (17 preclinical HD mutation-positive, 13 mutation-negative).
• Tensor based morphometry (TBM) was used to analyze statistically significant changes in regional grey and white matter volume.
• TBM estimates regional tissue volume change by analyzing the deformation field warping serial MRI scans.

Main Results:

• Progressive regional grey matter atrophy was observed in mutation-positive subjects compared to mutation-negative subjects over 2 years.
• No significant clinical progression was noted during the study period.
• Significant grey matter volume loss was localized to the bilateral putamen, globus pallidus externa, left caudate nucleus, and left ventral midbrain (substantia nigra region).

Conclusions:

• Longitudinal statistical imaging can demonstrate significant progression of brain atrophy in HD carriers before substantial clinical decline.
• These imaging measures are consistent with previous cross-sectional studies of HD pathology.
• This technique offers a potential method to assess the efficacy of disease-modifying drugs in slowing HD progression prior to clinical onset.