Disrupted coupling between salience network segregation and glucose metabolism is associated with cognitive decline in Alzheimer's disease – A simultaneous resting-state FDG-PET/fMRI study

The aberrant organization and functioning of three core neurocognitive networks (NCNs), i.e., default-mode network (DMN), central executive network (CEN), and salience network (SN), are among the prominent features in Alzheimer’s disease (AD). The dysregulation of both intra- and inter-network functional connectivities (FCs) of the three NCNs contributed to AD-related cognitive and behavioral abnormalities. Brain functional network segregation, integrating intra- and inter-network FCs, is essential for maintaining the energetic efficiency of brain metabolism. The association of brain functional network segregation, together with glucose metabolism, with age-related cognitive decline was recently shown. Yet how these joint functional-metabolic biomarkers relate to cognitive decline along with mild cognitive impairment (MCI) and AD remains to be elucidated. In this study, under the framework of the triple-network model, we performed a hybrid FDG-PET/fMRI study to evaluate the concurrent changes of resting-state brain intrinsic FCs and glucose metabolism of the three NCNs across cognitively normal (CN) (N = 24), MCI (N = 21), and AD (N = 21) groups. Lower network segregation and glucose metabolism were observed in all three NCNs in patients with AD. More interestingly, in the SN, the coupled relationship between network segregation and glucose metabolism existed in the CN group (r = 0.523, p = 0.013) and diminished in patients with MCI (r = 0.431, p = 0.065) and AD (r = 0.079, p = 0.748). Finally, the glucose metabolism of the DMN (r = 0.380, p = 0.017) and the network segregation of the SN (r = 0.363, p = 0.023) were significantly correlated with the general cognitive status of the patients. Our findings suggest that the impaired SN segregation and its uncoupled relationship with glucose metabolism contribute to the cognitive decline in AD.