They did show that both early-onset and LDK378 ALK inhibitor late-onset AD patients both showed lower functional connectivity within the DMN when compared to age-matched controls, but found this in frontal regions, where we found this in posterior cingulate cortex. The conflicting results are difficult to explain, but could be due to the different techniques used to establish functional connectivity, which is discussed below. In the present study, lower functional connectivity within both left and right dorsal-visual system was seen in early-onset compared to late-onset AD patients. For the right dorsal-visual system this was observed in right angular-, middle frontal gyrus and occipital cortex. For the left dorsal-visual system the same regions were found, with the exception of the middle frontal gyrus. The occipital cortex, besides posterior regions, has also been reported to show more severe hypometabolism and reduced brain activity measured with EEG in early-onset AD. Interestingly, hypometabolism of the middle frontal gyrus have been found associated with poorer performance on the executive system in working memory in early-onset AD. The dorsal-visual system is supposedly involved in spatial awareness and guidance of actions. Similar to our results, Gour et al. found lower functional connectivity in early-onset AD patients within the dorso-lateral prefrontal network compared to late-onset AD, which was observed in the anterior cingulate, precentral gyrus, inferior and superior frontal cortex. In addition, Gour et al. also identified the cuneus, precuneus and inferior parietal cortex, which was not replicated by the present study. Lower functional connectivity in early-onset AD patients included areas that are vulnerable in these patients but also extended well beyond these regions. This is in line with the hypothesis that functional changes precede atrophy. Functional connectivity measures functional integrity of spatially distinct brain regions. Local disturbances could therefore have widespread effects. Within the auditory system, lower functional connectivity in early-onset AD was found within right Heschl’s gyrus, which processes auditory stimuli and is involved in semantic tasks. This might explain why early-onset AD patients present more often with language problems than lateonset AD patients. Functional connectivity of the pre/ postcentral gyrus was affected in early-onset AD within the sensory-motor system.