A Multimodal Neuroimaging Approach to Investigate Interindividual Differences in Huntington’s Disease
Huntington’s disease is a genetic neurodegenerative disorder which is comprised of a myriad of motor, cognitive and psychiatric disturbances. Despite being caused by a single genetic mutation, it presents a high degree of phenotypic heterogeneity regarding the prominence of each type of symptom. Understanding the sources of this variability is vital in order to be able to develop different biomarkers for distinct clinical manifestations and, ultimately, develop more personalised treatments.
However, the traditional approach in neuroimaging studies has been to consider patients with Huntington’s disease as a homogenous group, placing special emphasis in finding common brain alterations when comparing patients with healthy controls. Although this approach has provided valuable information regarding the main brain structures affected in Huntington’s disease, it has not been able to account for interindividual differences in clinical manifestations among patients.
This doctoral thesis employs a distinct approach, investigating sources of interindividual differences in symptom prominence. Two main sources are explored: neural integrity and lifestyle factors. Importantly, lifestyle factors in turn affect neural integrity. With the aim of characterizing the sources of phenotypic interindividual differences in Huntington’s disease, we used a combination of different magnetic resonance imaging (MRI) modalities as well as a battery of questionnaires and neurological, neuropsychological and psychiatric assessments in order to investigate the relationship between neurobiological alterations, environmental factors and clinical symptoms.
The results of the current doctoral thesis shed light on the sources of interindividual differences in motor, cognitive, and psychiatric alterations in Huntington’s disease, providing a new perspective in which clinical heterogeneity of the disease is not disregarded, but rather is appreciated as a way to achieve more personalised treatments that may be specifically tailored to each patient.