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Systemic inflammation is linked to default mode network functional connectivity in mild alzheimer's disease and mild cognitive impairment

      Introduction: The default mode network (DMN) is early affected in AD. Inflammatory processes also play a role in pathological AD cascade, but its relationship with changes in the DMN is still unknown. We aimed to investigate the relationship between inflammatory cytokines and DMN functional connectivity (FC) in aMCI and AD patients.
      Methods: 34 aMCI (positive CSF biomarker) and 30 mild AD patients were included. Images were acquired on a 3.0 T MRI scanner. DMN mask was used as a template to extract each patients FC value of the DMN subregions. We performed multiple regression tests, adding inflammatory cytokines (IL-1B, IL-6, IL-8, IL-10, IL-12, TNF-α) as independent variables and DMN regions FC values as dependent variables.
      Results: In the aMCI group, medial parietal region FC correlated with age (p = 0,004, t = -3,38) and IL 10 (p = 0,03; t = -2,25, model R2 = 0,50). The frontal medial region FC correlated with age (p = 0,03; t = -2,23), IL 8 (p = 0,001; t = -3,71) and TNF-α (p = 0,01; t = 2,71, model R2 = 0,53) and the temporal region FC correlated with TNF-α (p = 0,001; t = 3,71) and age (p = 0,02; t = -2,47, model R2 = 0,51). Regarding the AD group, the medial temporal region FC correlated only with IL 6 (p = 0,008; t = -3,04, model R2 = 0,39).
      Conclusions: We showed for the first time that systemic inflammation predicts FC in the DMN of aMCI and AD patients.