We used a measure of physiological nonlinear connectivity, namely lagged phase synchronization, to determine differences in resting-state functional connectivity in patients with AD compared with elderly controls, and to assess the effects of APOE genotype on this activity. Abnormalities in cortical oscillations were also explored. Patients with AD exhibited a significant decrease in alpha1 oscillations in parieto-occipital regions compared with controls, and those carrying the APOE-4 allele had reduced alpha1 activity in the left inferior parietal and temporo-occipital cortex relative to noncarriers. The patients showed a pattern of decreased alpha2 lagged phase synchronization between the medial frontal/parietal region and the left temporal and the bilateral inferior parietal cortex, along with increased connectivity in the theta band in different cortical regions, where temporal connections were particularly compromised. Some of these functional connections in the theta band correlated negatively with the MMSE scores. Functional network disruption in patients with early AD carrying the APOE-4 allele was characterized by decreased interhemispheric alpha2 connectivity between frontal and parieto-temporal areas compared with noncarriers. There were no APOE-4-related connectivity abnormalities in the subgroup of patients with moderate/severe AD.
