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Normal cognitive function relies on efficient communication between brain regions. In treatment trials in Alzheimer's Disease (AD), an improvement of these impaired functional interactions could provide biological support for the potential efficacy of the drug. In the phase 2a SAPHIR-trial in early AD with PQ912, a glutaminylcyclase inhibitor, electroencephalography (EEG) analysis showed a significant improvement of global relative theta power in the intervention group compared to placebo. However, functional connectivity (FC) measured by the global phase lag index (PLI) did not improve. PLI may not be sensitive enough for the detection of small effects. Therefore, we compared the PLI with the amplitude envelope correlation with leakage correction (AEC-c), a presumably more sensitive FC measure to capture potential treatment effects. Data was used from the multicentre SAPHIR-trial. Patients with mild cognitive impairment to mild dementia both due to AD underwent 12 weeks of placebo or PQ912 treatment. Eyes-closed task free EEG was measured at baseline and follow-up (PQ912 n=47, placebo n=56). FC was measured using AEC-c and PLI in the delta (0.5-4Hz), theta (4-8Hz), alpha (8-13Hz) and beta (13-30Hz) frequency band. Change in FC was compared between treatment groups by t-test and ANCOVA using two models of covariates. Pearson's correlation coefficients were calculated between the change in FC measures and global relative theta power. A significant difference in change of global AEC-c in the alpha frequency band was found between treatment groups (mean change: placebo=-0.0047±0.0189 versus PQ912=0.0085±0.0252, t-test: p=0.004, Cohen's d=0.58) indicating an increased global FC after treatment. The effect remained significant when corrected for sex, country, ApoE ε4 carriage, age, baseline value (model 1; p=0.006) and in addition change in relative alpha power (model 2; p=0.004). There was no correlation between change in global relative theta power and global AEC-c in the alpha band (r=0.152, p=0.124). No significant differences between treatment groups were found using the PLI. Functional connectivity, measured with AEC-c in the alpha frequency band, significantly improved after PQ912 treatment in early AD, independent of baseline functional connectivity and relative power. AEC-c may be a robust and sensitive FC measure for detecting treatment effects.