EEG-based graph network analysis in relation to regional tau in asymptomatic Alzheimer's disease

Tau aggregation in early affected regions in the asymptomatic stage of Alzheimer's disease marks a transitional phase between stable asymptomatic amyloid positivity and the clinically manifest stage. How this early region tau aggregation covertly affects brain function during this asymptomatic stage remains unclear. In this study, 83 participants underwent a 128 electrodes resting-state EEG, a dynamic 100 min tau PET scan (¹⁸F-MK6240), an amyloid PET scan, a structural T1 MRI scan and neuropsychological assessment. Tau PET data quality control led to a final sample of 66 subjects. Based on the clinical and cognitive status, amyloid and tau PET biomarkers, the group was composed of 37 cognitively unimpaired amyloid negative subjects, 14 cognitively unimpaired amyloid positive subjects and 15 patients with prodromal Alzheimer's disease. We calculated the average undirected weighted Phase Lag Index in the alpha frequency band with eyes closed and used this as weights for the graph and analysed the global clustering coefficient and characteristic path length in sensor space. As a primary objective, we assessed how these global graph measures correlated with tau PET values, in an a priori defined early metaVOI, comprised of the entorhinal and perirhinal cortex, hippocampus, parahippocampus and fusiform cortex. As secondary analyses, we investigated which specific brain regions were mainly implicated, what the contribution was of amyloid, the effect of electrode density and the relation to cognitive performance. In the overall group and within the cognitively unimpaired amyloid positive subgroup, tau aggregation was associated with a decrease in global clustering coefficient and an increase in characteristic path length. These changes reflect the initial disintegration of the small-world brain network during the transitional phase, even before clinical symptoms are apparent. The correlations are most prominent in the perirhinal cortex, indicating that global deterioration of the network is already present early in the Alzheimer's disease pathology. We obtained similar results with only taking 64 electrodes into account. To conclude, we found that in the asymptomatic stage of Alzheimer's disease, tau PET load in medial temporal cortex is associated with global electrophysiological measures of network disintegration. The study demonstrates the potential value of high-density EEG in the era of biologically defined Alzheimer's disease for characterizing brain function in the asymptomatic stage.