E09 Hybrid brain positron emision tomography – magnetic resonance imaging using flurodeoxyglucose (FDG – PET/MRI) in premanifest huntingtons disease gene-expansion

Background Huntington’s disease (HD) is an autosomal dominantly inherited neurodegenerative disorder, caused by an expansion of a trinucleotide (CAG) repeat in the huntingtin gene. There is no cure and only sparse symptomatic treatment. Structural brain imaging is the most applied and well documented technique to demonstrate longitudinal structural changes in premanifest and manifest HD gene-expansion carriers. Changes in the striatum are registered as far as 15 years before symptom onset with MRI. PET studies have found hypometabolism in the Caudate nucleus, Putamen and the temporal and frontal cortex years before clinical diagnosis along with hypermetabolism in Thalamus prior to symptom onset. Aims By a hybrid brain PET-MRI using FDG, we wished to simultaneously characterize the structural and metabolic brain changes in premanifest HD gene-expansion carriers and address the question whether changes in the metabolism precede the structural changes. Methods We recruited 21 premanifest HD gene-expansion carriers and 17 controls from the Neurogenetics Clinic, Danish Dementia Research Centre, Rigshospitalet, Denmark. We included individuals with CAG repeat ≥39 and a Unified HD Rating scale total motor score ≤5. Results We found a significantly lower (p=0.028) striatal metabolism in the HD gene expansion carrier group compared to gene-negative controls, while there was no significant striatal volume difference. We found a significant correlation between both striatal metabolism and CAP score and striatal volume and CAP score. The higher the CAP score, the lower the metabolism and striatal volume. We also found a significant positive association between striatal metabolism and MRI volume. Conclusions Our results suggest that striatal hypometabolism precedes atrophy; however longitudinal studies on larger cohorts using hybrid FDG-PET/MRI are needed to precisely assess the changes and evolution in time.