The first studies in this area showed that there is decreased precuneus deactivation during tasks [32] and decreased DMN connectivity [33] in AD. Since the regions in the DMN (specifically, the hippocampus) are related to episodic memory, DMN is the most studied view more network in AD [33]. Studies have also shown decreased functional synchrony in the hippocampus [34] and reduced connectivity of the hippocampus to the rest of the DMN [35]. As mentioned above, several consistent ICNs other than the DMN operate synchronously in the resting brain (for example, motor function, visual processing, executive functioning, auditory processing, and episodic memory).

Sorg and colleagues [36] were the first to study eight consistent networks in subjects with increased risk for AD by using ICA and found that two networks, namely the DMN and executive attention, had significantly reduced connectivity in patients with amnestic MCI when compared with cognitively normal (CN) subjects. Several task-associated studies have also investigated the effect of AD on several components of the memory networks – a key domain affected in AD [37-39]. As a heteromodal region – a hub for the majority of the information processing in the brain and a region of significant hypometabolism and amyloid deposition in AD – precuneus/posterior cingulate (PPC) is the most studied region in fMRI AD studies [40]. There has been evidence that disease-related regional coherence of the region is decreased [41] and that functional disconnection of this region precedes atrophy [42].

Whereas some studies have shown reduced connectivity of this region to the brain early in the disease process [43,44], others have found notable increased connectivity [43,45-47]. Recent papers have also been trying to investigate whether the PPC connectivity changes are due to regional pathology. Frings GSK-3 and colleagues [48] found that patients with early frontotemporal dementia have PPC connectivity changes similar to those of patients with AD or MCI, suggesting that PPC disconnection is a function of a lack of connectivity and not local pathology. Mormino and colleagues [49] found that, even though DMN is altered by increasing global amyloid levels, there was little effect of regional amyloid levels on regional functional connectivity.

Different studies have used different methodologies that are quantitatively dissimilar and have used different populations to investigate this question, making it difficult to interpret the overall effect of AD on network connectivity. However, recently, the field has been PF-2341066 moving toward the understanding that there is reduced DMN connectivity posteriorly with concomitant frontal lobe increases in the DMN [29] and the salience network [50,51]. The interpretation of these reciprocal changes is a matter of ongoing investigation [52].