Abstract
BackgroundLate-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are two different diseases associated with a high risk of developing Alzheimer’s disease (AD). Both diseases are accompanied by dysregulation of inflammation. However, the differences and similarities of peripheral inflammatory parameters in these two diseases are not well understood.MethodsWe used Luminex assays to measure 29 cytokines simultaneously in the plasma of two large cohorts of subjects at high risk for AD (23 LLD and 23 aMCI) and 23 normal controls (NCs) in the community. Demographics and lifestyle factors were also collected. Cognitive function was evaluated with the Chinese versions of the Montreal Cognitive Assessment (C-MoCA) and neuropsychological test battery (NTB).ResultsWe observed a remarkably increased level of IL-6 in the plasma and reduced levels of chemokines (CXCL11 and CCL13) in the LLD group compared with the aMCI group. The LLD group also showed lower levels of CXCL16 than the NC group. Furthermore, altered cytokine levels were associated with abnormal results in neuropsychological testing and Geriatric Depression Scale scores in both the LLD and aMCI groups. Notably, combinations of cytokines (IL-6 and CCL13) and two subitems of C-MoCA (orientation and short-term memory) generated the best area under the receiver operating characteristic curve (AUROC = 0.974).ConclusionA novel model based on proinflammatory cytokines and brief screening tests performs with fair accuracy in the discrimination between LLD and aMCI. These findings will give clues to provide new therapeutic targets for interventions or markers for two diseases with similar predementia syndromes.
Highlights
It is expected that by 2050, the number of people with dementia may exceed 131 million
Clinical diagnosis of amnestic mild cognitive impairment (aMCI) was adapted from Petersen et al [22], requiring evidence of a definite decline in memory and without significant impact on daily living, with the severity of symptoms or consequent functional limitation not meeting the criteria for the diagnosis of dementia in DSM-V; a diagnosis of normal control was made if participants demonstrated no evidence of cognitive decline as compared with their baseline cognitive functions on clinical interview and assessment
The control group had significantly higher mean CMoCA scores than the other groups, and MDS, Category Fluency Test (CFT), and Controlled Word Association Test (COWAT) scores were lower in the aMCI and depression groups than in the control group
Summary
It is expected that by 2050, the number of people with dementia may exceed 131 million. Dysfunctional cytokines have been associated with both neurodegenerative and psychiatric disorders, including AD, mild cognitive impairment, schizophrenia, depression, and bipolar disorder [7, 8]. Increased inflammatory markers such as soluble tumor necrosis factor receptor 2 (sTNFR2), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) have been reported in patients with dementia compared with controls [9, 10]. Late-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are two different diseases associated with a high risk of developing Alzheimer’s disease (AD). Both diseases are accompanied by dysregulation of inflammation. The differences and similarities of peripheral inflammatory parameters in these two diseases are not well understood
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