Functionele connectiviteit in het preklinisch en prodromaal stadium van de ziekte van Alzheimer

Alzheimer's disease is preceded by a long asymptomatic phase during which amyloid β (Aβ) deposition and tau aggregation occur before cognitive symptoms emerge. Understanding how these pathological changes affect brain connectivity is critical for early detection and intervention. This thesis examines functional connectivity alterations across biologically defined stages of AD using a multimodal approach integrating high-density EEG, resting-state fMRI, tau and amyloid PET imaging, and neuropsychological assessments. Findings reveal that tau pathology in medial temporal regions is associated with disrupted EEG network organization, reflected by reduced clustering and increased path length in the alpha band, particularly in cognitively unimpaired individuals with amyloid positivity. These changes suggest early disintegration of small-world network properties prior to clinical decline. In contrast, fMRI analyses indicate hyperconnectivity in prodromal Alzheimer's disease, with increased global integration and nodal strength in regions both vulnerable and typically spared by early pathology. Tau burden correlated with hyperconnectivity in distant cortical areas, implying network-level adaptation to impending dysfunction. No significant associations with cognitive performance were observed, reinforcing the concept of preclinical network reorganization. This work highlights the complementary insights of EEG and fMRI in characterizing connectivity changes linked to Alzheimer's disease pathology. By combining functional and molecular imaging within the same individuals, the thesis advances understanding of early network alterations and supports the potential of multimodal biomarkers for preclinical diagnosis and monitoring.