Motivation: Juvenile-onset Huntington Disease (JoHD) represents 4-10% of HD cases, has worse prognosis and psychiatric rather than motor symptomatology, compared to the adult form (AoHD). No study has yet investigated morphological and metabolic changes comparing these two forms with PET-MRI. Goal(s): Are brain structural and metabolic changes different between patients with JoHD and AoHD? Do they evolve differently?Approach: PET/MRI was acquired on AoHD and JoHD patients. Cortical and subcortical hybrid characteristics were compared between groups and overtime. Results: POHD had the most remarkable striatum volume loss at baseline. Interestingly, POHD brain cortex volume was relatively spared at baseline if compared to AOHD patients. Impact: This study provides first evidence that disease-related degeneration in JoHD first affects subcortical regions, where atrophy is more severe compared to AoHD, and ultimately spreads to the cortex, with faster rates of thinning and glucose metabolism changes compared AoHD.

Brain structure and glucose metabolism in juvenile and adult-onset Huntington disease: a cross-sectional and longitudinal PET/MR study