Biomarkers in the differential diagnosis of dementia: cerebrospinal fluid compounds- and nuclear molecular imaging tracers

Abstract

The aim of this thesis is to examine biomarkers in the differential diagnosis of dementia, a prevalent brain disease. Cerebrospinal fluid (CSF) biomarkers are useful to diagnose Alzheimer’s Disease (AD). The AD-CSF-biomarker-profile is characterized by decreased Amyloid-beta and increased (phosphorylated) Tau. CSF biomarkers are investigated in a broad population of a memory clinic and we found overlap in The AD-CSF-biomarker-profile and other dementias, especially Lewy Body Dementia (DLB), Corticobasal degeneration, Frontotemporal dementia (FTD) and vascular dementia. Although CSF biomarkers correctly diagnose AD, more specific CSF biomarkers are needed to differentiate from other types of dementia. CSF α-Synuclein was assessed as a biomarker to differentiate DLB and Parkinson Disease from AD, but failed for this diagnostic purpose and other biomarkers are needed. The positron emission tomography (PET) biomarkers in dementia are AD specific amyloid PET ligands, as [11C] PiB and non-specific topographic marker for synaptic dysfunction as [18F]FDG. In the ‘dual PET’ study, PiB and FDG PET scans are investigated in AD and other dementias. Accumulation of PiB and parietal-temporal hypometabolism at FDG PET scan are ‘classic’ for AD. Atypical FDG PET patterns are associated with a ‘spectrum’ of neurodegenerative dementias, as corticobasal syndrome, primary progressive aphasia and posterior cortical atrophy or other types of dementias as DLB or FTD. Combined semi-quantitative multivariate analysis techniques may be helpful in FDG-PET pattern recognition. A subgroup of AD patients is observed with the phenomenon of crossed cerebellar diaschisis; unilateral cerebellar hypometabolism as a remote effect of supratentorial dysfunction of the brain in the contralateral hemisphere. Dual-tracer study in AD shows that metabolism and blood flow are correlated, both providing an index for neuronal function.