Altered Proinflammatory Cytokines Distinguish Elderly with Major Depressive Disorder from Amnestic Mild Cognitive Impairment in a Chinese Population

Abstract Background: Research evidence has shown that late life depression(LLD)and amnestic mild cognitive impairment(aMCI)are both related to dementia and usually accompanied by inflammatory dysregulation, but few studies have compared the levels of chemokines and cytokines between these two disorders. In this cross-sectional study, we aimed at identifying differences in neuro-inflammation between patients with prodromal stage of AD (amnestic mild cognitive impairment, aMCI; Late life depression LLD) and the normal controls (NC).Additionally, the potential association between cognitive function and cytokines characteristics was evaluated.Methods: Using Luminex assays,we simultaneously measured 29 cytokines,including 6 CXC chemokine ligand(CXCL5,CXCL6,CXCL8,CXCL9,CXCL11,CXCL16),15 CC chemokine ligand(CCL1, CCL2,CCL3,CCL7, CCL8, CCL11, CCL13,CCL15,CCL17, CCL19,CCL20, CCL23, CCL24, CCL25, CCL27), IL-1β, MIP-2, IFN-γ, VCAM-1, IL-2, IL-4, TNF-α and IL-6 in plasma of subjects. Demographics, cognitive function and lifestyle factors were also collected. All subjects(n=69, 23 each group)were age- and gender-matched outpatients with LLD or aMCI without dementia(based on DSM-IV criteria)and normal controls(NC)in community. The Chinese versions of Montreal Cognitive Assessment(MoCA) and neuropsychological test battery (NTB) were used to evaluate the cognitive function in participants.Results: LLD patients showed remarkably higher level of IL-6 than the aMCI and NC groups. We also observed five CC chemokines (CCL2,CCL17,CCL15, CCL13and CCL5) and four CXCs (CXCL5,CXCL6,CXCL16 and CXCL11) were decreased in patients with LLD. In addition, CXCL5 and VCAM-1 were correlated with age and clinical characteristic with gender difference. Importantly, using two parameters(IL-6 and CCL13) could effectively distinguish LLD from aMCI with an area under curve of 0.809(95% CI 0.68-0.93).Conclusion: Under conditions of neuro-inflammation, distinct dysregulated pro-inflammatory cytokine and chemokines were associated with patients with predementia stage LLD and aMCI.. Our study showed that the model based on the pro-inflammatory cytokine could distinguish LLD from aMCI. These novel findings will give new clues to provide new therapeutic target for intervention or a marker for two diseases with similar pre-dementia syndromes.