A successful connection of this hypothesis with the β-amyloid hypothesis of AD may require any kind of upregulation of β-amyloid during neural activity. Indeed, there are some studies that may support such a link. Cirrito et al showed that β-amyloid increased following stimulation of the brain in mice expressing human amyloid precursor protein. They demonstrated that β-amyloid in the brain interstitial fluid was dynamically and directly influenced by synaptic activity on a timescale of minutes to hours.75 This observation suggests that synaptic activity can increase the presence of extracellular β-amyloid. A further supporting observations come from a new PET method of mapping glycolysis based on measuring the ratio of oxygen to glucose consumption. Vlassenko et al calculated the spatial distribution of the regional glucose use apart from that entering oxidative phosphorylation.76 The so-called “aerobic glycolysis,” the process by which glucose is metabolized into cellular energy, might be more closely associated with neuronal or synaptic activity than the mere glucose utilization. In humans, aerobic glycolysis represents 35% of the glucose turnover in the brain of a newborn and 19% of the glucose used in the brain of an alert adult.77 Certain association areas in the human brain retain elevated levels of aerobic glycolysis in adulthood related to cognitive functions such as the dorsolateral prefrontal cortex, which is associated with working memory, and the ventromedial prefrontal cortex, the dorsomedial prefrontal cortex, the posterior cingulate cortex, the inferior parietal lobe, the lateral temporal cortex, and the hippocampus.62,76-79 In normal young adults aerobic glycolysis correlated positively and spatially with β-amyloid deposition observed in individuals with Alzheimer's dementia and cognitively normal participants with already elevated β-amyloid levels, suggesting a possible link between regional aerobic glycolysis in young adulthood and later development of AD pathology. The map of resting-state glycolysis correlated remarkably well with the distribution of amyloid plaques.76 On the other side DMN activity and coherence is diminished during deep sleep. Here only partial network involvement was observed, with apparent decoupling of frontal areas from the DMN80 An important study by Kang et al used in vivo micro-dialysis in mice and found that the amount of pamyloid in the interstitial brain fluid correlated positively with wakefulness. The amount of interstitial β-amyloid also significantly increased during acute sleep deprivation. Furthermore, chronic sleep restriction significantlyincreased, and a dual orexin receptor antagonist decreased β-amyloid plaque formation in human amyloid precursor protein transgenic mice.81 Interestingly, sleep deprivation, which is known to impair memory storage and retrieval, reduces default mode network connectivity and anti-correlation with the default attention networks during rest and task performance.82 Regarding AD subtypes, Lehmann et al report that the posterior DMN and precuneus network are commonly affected in all AD variants, whereas syndrome-specific neurodegenerative patterns are driven by the involvement of specific networks outside the DMN and characterize differentially early-onset AD (anterior salience network), logopenic variant of AD (language network), and posterior cortical atrophy (visual network).83Sleep and the functional connectome are overlapping research areas. Neuroimaging studies of sleep based on EEG-PET and EEG-fMRI are revealing the brain networks that support sleep. Such infraslow oscillations may organize sleep-dependent neuroplastic processes including consolidation of episodic memory, for example. Picchioni et al found positive correlations between the power in the infraslow EEG band and MRI blood oxygen level-dependent (BOLD) response in subcortical regions and negative correlations in the cortex. Robust negative correlations were detected principally in paramedian heteromodal cortices whereas positive correlations were seen in cerebellum, thalamus, basal ganglia, lateral neocortices, and hippocampus.84 Sleep has adaptive and recreating functions that uphold waking activity in humans and mammals in general. Our understanding of DMN activity and its regulation during sleep may be also important for our general understanding of phenomena like memory, arousal, and consciousness.80,84-86 Clinically sleep-wake disturbances such as increased inadvertent daytime napping and insomnia at night affect 25% to 40% of patients with mild-to-moderate AD.