Imaging of Brain Connectivity in Dementia: Clinical Implications for Diagnosis of its Underlying Diseases

In this thesis we investigated the use of advanced magnetic resonance imaging (MRI) techniques in identifying subtle brain abnormalities, associating brain abnormalities with disease symptomatology, and improving early (differential) diagnosis in several diseases underlying dementia. Presenile dementia (occurring before 65 years of age) is a neurodegenerative disorder affecting white matter (WM) and grey matter (GM) in different regions of the brain. The two most common underlying diseases are Alzheimer’s disease (AD) and frontotemporal dementia (FTD). FTD is the umbrella term for several types of dementia, such as behavioural variant FTD (bvFTD) and semantic dementia (SD). Additionally, phenocopy frontotemporal dementia (phFTD), a rare syndrome clinically similar to bvFTD, may also belong to this FTD spectrum. In early stages of these diseases, symptoms may still be mild or unspecific. Consequently, early-stage (differential) diagnosis can be difficult. MRI of the brain supports diagnosis, but may still appear normal or show unspecific brain abnormalities in early stages of dementia. More advanced MRI techniques may aid diagnosis by detecting subtle abnormalities that remain unrevealed using conventional (structural) MRI. Additionally, advanced MRI can be quantified, which allows for comparing patients to reference values of the healthy population, and allows for combining WM and GM measures to investigate relations between subtle WM and GM changes in dementia. In this thesis several advanced MRI techniques were explored, specifically diffusion tensor imaging (DTI), resting state functional MRI (rs-fMRI) and arterial spin labelling (ASL). DTI and rs-fMRI can be used to assess brain connectivity in terms of respectively WM microstructure and functional connectivity of resting state networks. Arterial spin labelling can be used to assess whole-brain or region-specific perfusion in GM. Additionally, advanced post-processing tools can be applied to conventional (structural) MRI, which may allow for identifying smaller GM volume changes. The main findings of this thesis allow for the conclusion that advanced MRI techniques identify subtle brain abnormalities in AD, bvFTD, SD and phFTD, that are not otherwise detected using conventional (structural) MR imaging. These subtle brain abnormalities aid to the understanding of brain processes in dementia, and especially DTI and ASL may aid clinical diagnosis and differentiation of the dementia subtypes