Functional Neuroimaging in Dementia

Dementia refers to a clinical syndrome of cognitive deterioration and difficulty in the performance of activities of daily living. The most common cause of dementia is Alzheimer’s disease (AD), followed by vascular dementia (VaD) at old age and frontotemporal dementia (FTD) at young onset. Most dementia subtypes show a gradual decline in clinical and cognitive symptomatology, which enables us to identify subjects in a prodromal stage of dementia, referred to as mild cognitive impairment (MCI). As functional neuroimaging techniques provide a means to investigate (early) alterations in brain functioning, these techniques can aid research regarding dementia subtypes and prodromal dementia stages. The focus of this thesis was twofold. In a first chapter I studied the effects of cerebral small vessel disease (CSVD) on brain functioning and structural connectivity in MCI using functional MRI and diffusion tensor imaging. CSVD is a fairly common condition in elderly, which affects the small vessels of the brain supplying the white matter and deeper grey matter regions, visible on MRI as white matter hyperintensities and lacunar infarcts. CSVD contributes to cognitive and clinical symptoms in MCI, but the underlying mechanisms are unclear. The presence of CSVD was found to have a large effect on microstructural white matter integrity throughout the brain. Important fiber tracts for brain network functioning were found to be affected mainly by CSVD in MCI, while the presence of atrophy caused by neurodegenerative conditions did not have a large effect. We found that the presence and extent of CSVD in MCI was furthermore related to decreased medial temporal lobe activation, a brain region important for memory functioning, and decreased deactivation within a region known to be highly involved in the default mode network. These multimodal neuroimaging findings suggest that CSVD affects the microstructure of the white matter, as well as neural functioning during cognitive performance. We postulate that the mechanism through which CSVD affects cognition, or contributes to cognitive deterioration in MCI is neural network interference, as a consequence of damaging the interconnecting fiber tracts. A second focus of this thesis was investigating brain functioning in FTD, AD and progressive supranuclear palsy, using single-photon emission computed tomography (SPECT). Early discrimination between these neurodegenerative conditions during life is hampered by the fact that clinical and cognitive symptomatology can overlap. The use of quantitative analysis of perfusion SPECT neuroimaging may aid addressing these issues. We identified the functional substrate of episodic memory failure in the behavioural variant FTD (bvFTD), by comparing perfusion patterns in bvFTD patients with and without episodic memory impairment and early onset AD patients. BvFTD patients with memory impairment showed lower perfusion in the right temporal lobe, a brain region usually associated with AD. FTD patients and PSP patients showed a similar relationship between hypoperfusion in the anterior cingulate cortex and executive dysfunctioning. Concluding, we found that while the underlying disease or pathology type can differ, clinical and cognitive symptoms may overlap as a consequence of similarities in affected brain regions.

• View at Worldcat

Free Full Text ( Final Version , 3mb )