Premanifest Huntington's disease : a study of early biomarkers

Abstract

The general objective of this thesis was to investigate whether early clinical alterations and structural and functional brain markers could be detected in carriers of the Huntington__s disease gene (referred to as carriers) who are still without manifest motor signs. We aimed to detect brain deficits using MRI and found smaller basal ganglia volumes in carriers compared to non carriers. Also, we demonstrated an increased amount of hypointensities in basal ganglia of carriers and suggested this may reflect excessive iron deposition. Furthermore, we showed strong associations between MRI characteristics and clinical variables suggesting that a combination of these measures may shed more light on the contribution of different kinds of pathological processes to the changing phenotype. When using memory activation during EEG registration early funcional brain changes, reflected in reduced alpha power, could be demonstrated in carriers. Furthermore, remarkably strong associations were found between the P3 Event-Related Potential and basal ganglia volumes. Subtle clinical abnormalities in motor function, executive function and memory could be demonstrated in carriers, especially over time. This study showed that several biomarkers provide new and important information on premanifest HD. The mulitfactorial approach offers new insights into the relation between clinical phenomena and abnormalities in the neural substrate