Overall findings indicate that in addition to regional cortical dysfunction, there is impairment in resting-state functional connectivity in alpha and theta bands in AD. This activity affects various brain networks, where temporal lobe (i.e., fronto-temporal and parieto-temporal) connections are particularly compromised, and theta hyperconnectivity likely representing a compensatory mechanism. Although APOE-4 is associated with increased vulnerability to AD, as a genetic risk factor, it appears to have a negative impact on cortical rhythms and functional brain networks even after the development of the disease that is particularly manifested during the early stage of the disorder. The altered connectivity pattern in later stages might be determined by cognitive factors or disease-specific abnormalities. These findings warrant further investigation and suggest that the patterns of functional network disruption, as indicated by lagged phase synchronization measures, may potentially represent neurophysiological or phenotypic markers of AD, and aid in early detection of the disease.
