Evaluation and implementation of functional cerebral biomarkers in Alzheimer’s disease

The aim of this thesis was to evaluate and implement functional cerebral biomarkers in Alzheimer’s disease (AD) with respect to pathophysiology, disease severity, prognosis and treatment effect in medical trials. We focused on functional cerebral biomarkers that assess synaptic activity and functional connectivity using electroencephalography (EEG), magnetoencephalography (MEG) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET). In the different chapters a broad range of challenges associated with this topic was covered. We started by using FDG- PET to observe the effects of the experimental treatment of AD patients with the medical food Souvenaid, followed by EEG as treatment outcome measure in a trial with the drug PQ912. Next to the primary outcomes, the results of these studies revealed that more research was needed to observe which markers could observe reliable, reproducible and valid results and what the factors were that could influence their ability to do this. The EEG markers, rather than the FDG- PET markers, showed promising results. Therefore, we aimed to investigate the effects of sensitivity, reproducibility, heterogeneity of the population and treatment efficacy, while maintaining a well-defined study population and study design, on EEG biomarkers. We first investigated the reproducibility of AD related changes in functional connectivity captured by different measures in electroencephalography (EEG) and magnetoencephalography (MEG). Second, we evaluated the influence of subtypes of AD on various EEG measures and, on the other hand, we used EEG to find heterogeneity and to predict clinical progression.