Longitudinal Imaging of Regional Brain Volumes,SV2A,and Glucose Metabolism In Huntington's Disease

Background

Development of disease-modifying treatments for Huntington's disease (HD) could be aided by the use of imaging biomarkers of disease progression. Positron emission tomography (PET) with ¹¹C-UCB-J, a radioligand for the brain-wide presynaptic marker synaptic vesicle protein 2A (SV2A), detects more widespread brain changes in early HD than volumetric magnetic resonance imaging (MRI) and ¹⁸F-fludeoxyglucose (¹⁸F-FDG) PET, but longitudinal ¹¹C-UCB-J PET data have not been reported. The aim of this study was to compare the sensitivity of ¹¹C-UCB-J PET, ¹⁸F-FDG PET, and volumetric MRI for detection of longitudinal changes in early HD.

Methods

Seventeen HD mutation carriers (six premanifest and 11 early manifest) and 13 healthy controls underwent ¹¹C-UCB-J PET, ¹⁸F-FDG PET, and volumetric MRI at baseline (BL) and after 21.4 ± 2.7 months (Y2). Within-group and between-group longitudinal clinical and imaging changes were assessed.

Results

The HD group showed significant 2-year worsening of Unified Huntington's Disease Rating Scale motor scores. There was significant longitudinal volume loss within the HD group in caudate (?4.5% ± 3.8%), putamen (?3.6% ± 3.5%), pallidum (?3.0% ± 2.7%), and frontal cortex (?2.0% ± 2.1%) (all P < 0.001). Within the HD group there was longitudinal loss of putaminal SV2A binding (6.4% ± 8.8%, P = 0.01) and putaminal glucose metabolism (?2.8% ± 4.4%, P = 0.008), but these changes were not significant after correction for multiple comparisons. Premanifest subjects at BL only had significantly lower SV2A binding than controls in basal ganglia structures, but at Y2 additionally had significant SV2A loss in frontal and parietal cortex, indicating spread of SV2A loss from subcortical to cortical regions.

Conclusions

Volumetric MRI may be more sensitive than ¹¹C-UCB-J PET and ¹⁸F-FDG PET for detection of 2-year brain changes in early HD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.