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

• Published in: Movement disorders Vol. 38; no. 8; pp. 1515 - 1526
• Main Authors: Delva, Aline, Van Laere, Koen, Vandenberghe, Wim
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.08.2023; Wiley Subscription Services, Inc
• Subjects: 11C‐UCB‐J PET; 18F‐FDG PET; Basal ganglia; Cortex (frontal); Cortex (parietal); Globus pallidus; Glucose metabolism; Huntington's disease; Huntingtons disease; Magnetic resonance imaging; Metabolism; Movement disorders; Neuroimaging; Positron emission tomography; Putamen; structural MRI; synaptic density; synaptic density; 18F-FDG PET; structural MRI; Huntington's disease; 11C-UCB-J PET
• ISSN: 0885-3185; 1531-8257; 1531-8257
• DOI: 10.1002/mds.29501

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.