Huntington’s Disease (HD) is an inherited neurodegenerative disorder caused by a CAG (codon that codes for amino acid glutamine) repeat expansion in the huntingtin gene (HTT). The prevalence of HD varies by ethnic origin and occurs mainly in Caucasian populations. Clinically HD is characterised by progressive motor dysfunction, cognitive decline, and psychiatric disturbances and the onset of symptoms is inversely associated with the size of the CAG repeat expansion. Nonetheless, subclinical changes and pathological processes are thought to precede the initiation of clinical symptoms by several years and not all variation in symptom and disease onset is explained by CAG repeat length, in particular not non-motor symptoms, including apathy, depression, and cognitive decline. Therefore, identification of easily obtainable, reliable, and robust biomarkers of HD progression, moving away from the strong focus on HTT CAG repeat length alone, is crucial for the development and evaluation of disease- modifying treatments. The latter is the aim of the ambitious iMarkHD study in the form of neuroimaging (PET and MRI) changes and their link to extensive clinical phenotyping.
The aim of this project is to characterise a time path across different stages of HD for temporal changes in cognitive and neuropsychiatric symptoms in people with HD using dynamic connectivity MRI analysis. In addition, the student can champion specific elements of PET and MRI imaging and their association with clinical measures that are being collected as part of the iMarkHD study. During the project the PhD student will develop skills and knowledge related to analyses of MRI and PET data as well as statistical analyses related to clinical data and their association with neuroimaging outcomes. The students will develop knowledge for understanding research and interpreting data in applied settings, conduct methodologically sound research, and will disseminate research in public forums and through peer-reviewed publications.