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... Show moreThe 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 Show less
Early dementias are difficult to distinguish from normal age-related memory decline. In the preclinical stages of Alzheimer’s disease and Huntington’s disease, brain functions are already changing... Show moreEarly dementias are difficult to distinguish from normal age-related memory decline. In the preclinical stages of Alzheimer’s disease and Huntington’s disease, brain functions are already changing, but this is not directly visible from the outside. Many research is aimed at discovering early disease markers. However, research using EEG registration during conventional eyes closed conditions revealed little additional information. The yield of EEG research can be improved by probing the weakest spot, which, in case of dementia, is memory. Karin van der Hiele introduced memory tests during EEG registration and found that early abnormalities in brain functioning can then be observed in Alzheimer’s disease and Huntington’s disease. An interesting finding came to light: the EEG in dementia displays a lot of muscle activity which is normally filtered out. However, the researchers decided not to throw this activity away but to measure it. Interestingly, they found that the amount of muscle activity was related to cognition and to the number of depressive complaints. It may pay to keep an open mind regarding the nature of the parameter to be measured. Show less
