Poster 12: A Metabolic Network Associated with the Progression of Preclinical Huntington's Disease: Application of the Ordinal Trends Analysis to a Longitudinal PET Study

Abstract

Objective To characterize longitudinal changes in metabolic network activity during phenoconversion in preclinical Huntington's disease (pHD) patients. Background Metabolic changes accompanying phenoconversion in HD are not well understood. The ordinal trends (OrT) model is a novel multivariate voxel-based approach developed to identify and quantify progression-related networks in individual subjects (Habeck et al., 2005). We used serial PET imaging to examine activity of an OrT network during the transition from preclinical to symptomatic HD. Design/Methods Twelve pHD gene carriers (CAG repeat length, 41.6 ± 1.7; age, 46.8 ± 11.0 years; estimated years-to-onset, 10.3 ± 8.6 years) underwent FDG PET at baseline, 18, and 44 months. Of these 12, four became symptomatic by 44 months. Four patients (2 phenoconverted and 2 non-phenoconverted) were additionally scanned at 68 months. Results Using OrT, we identified a highly significant spatial covariance pattern associated with progression in preclinical HD ( p p Conclusion We found that OrT network activity increased in pHD subjects followed up to 68 months. This increasing trend was found in subjects who either did or did not phenoconvert during the follow-up period. However, the phenoconverters exhibited a higher level of network activity than the non-phenoconverters both before and after clinical onset. Thus, the OrT network is likely to be a useful biomarker of progression in preclinical HD, which may improve the prediction of symptom onset in mutation carriers.