Morphological alterations in frontotemporal dementia

Sammanfattning: The present thesis explores alterations in brain morphology in the neurodegenerative disorder of frontotemporal dementia (FTD). With the aim to improve the clinical diagnostics of FTD, we explored the diagnostic potential of measuring morphological alterations in the white matter by diffusion tensor imaging (DTI)- MRI, compared with the more commonly used assessment of grey matter thickness and volume. DTI-MRI was better at separating FTD cases from controls than grey matter parameters, and may thus be a promising supplementary imaging tool for the diagnostic work in FTD. We used DTI in combination with grey matter imaging to explore the morphological underpinnings of one of the central behavioural symptoms in FTD, disinhibition. Our results show that this symptom appears related to the integrity of an orbitofrontal-temporal network, as opposed to the prevailing view of a degeneration of the orbitofrontal cortex. An important question in FTD is what constitutes the morphological link between the molecular pathologies and the characteristic frontotemporal pattern of cortical degeneration. The von Economo neurons (VENs), are a particular type of neurons that are proposed to constitute this link. We confirm results from others, showing that these neurons are selectively degenerated in FTD. In addition we show that these neurons are more afflicted than pyramidal neurons in the superficial cortical layers, previously thought to be the most selectively degenerated in the cortex of FTD. The findings presented in this thesis will hopefully contribute both to improved diagnostics, understanding of clinico-pathological relationships, and of the pathophysiology of this condition.