Objective: To understand the relationship between progression of the clinical symptoms and patterns of brain hypometabolism progression in a large cohort of Huntington’s disease (HD) patients.

Background: Striatal atrophy is present in the preclinical phase of HD and extends to the posterior cortical regions. Atrophy has been correlated with clinical markers. However, atrophy is a late marker of disease severity, related to neuronal death. FDG-PET imaging studies have reported discordant topographical changes of brain hypometabolism compared to cortical atrophy in HD patients. Regional brain metabolism has been transversally correlated with clinical symptoms but no longitudinal study has used FDG-PET to analyze the relationships between evolution of brain metabolism and clinical markers.

Method: Data were extracted from MIG-HD trial (NCT00190450). Thirty-four HD patients were included with a total motor score (TMS) >5 and a total functional capacity (TFC) score >9.

Motor, functional and cognitive evaluations were performed at inclusion and over follow up for 4 years. PET imaging was performed at 12 (PET₁), 32 (PET₂) and 52 months (PET₃) after inclusion.

Regions of interest were clustered according to their metabolism transversally at PET₁ and longitudinally over the whole follow-up using a weighted gene correlation network analysis (WGCNA). Metabolism in each cluster was correlated to the clinical variables at PET₁ using WGCNA and evolution of brain metabolism in each cluster was also correlated to the evolution of the clinical parameters.

Results: There was a significant overall reduction of metabolism which was more pronounced in subcortical and anterior cortical regions with relatively spared posterior cortical areas over the whole follow-up.

Significant correlations at PET₁ were mainly observed between metabolism in basal ganglia and TFC, UHDRS-dependance, motor scores, cUHDRS, Mattis dementia rating scale (MDRS) and categorial verbal fluency. Conversely, main correlations over follow-up were observed between the evolution of metabolism in cortical areas and several cognitive scores such as categorial fluency, figure cancellation task, MDRS and SDMT.

Conclusion: Our data suggest that striatal hypometabolism plays a major role in the cognitive deficits at the early stage of HD, whereas further progression of cognitive decline is more related to the spreading of hypometabolism from anterior to posterior cortical areas.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-relationship-between-brain-metabolism-and-clinical-changes-in-huntingtons-disease/