Mediation Effects of IL-1β and IL-18 on the Association Between Vitamin D Levels and Mild Cognitive Impairment Among Chinese Older Adults: A Case–Control Study in Taiyuan, China

Abstract

ObjectiveMild cognitive impairment (MCI) is a common, chronic, and complex disease in the elderly, which is often influenced by a variety of factors that include nutrition and inflammation. This study was undertaken to evaluate the mediation effects of inflammation on the association between vitamin D levels and MCI.MethodsWe explored the associations of inflammation and cognitive impairment related to 25(OH)D3 deficiency among 360 older people from the communities in China. Demographic characteristics, lifestyle, and health status were investigated by questionnaire, cognitive function was detected by MoCA, and plasma 25(OH)D3, interleukin-1β (IL-1β), and interleukin-18 (IL-18) were measured by ELISA. Spearman’s correlation analysis and logistic regression analysis were used to analyze the relationship among 25(OH)D3, IL-1β, and IL-18 in the MCI group and the control group and further to analyze the relationship between 25(OH)D3 and inflammatory factors in the MCI group. Finally, mediation analysis was performed to evaluate whether inflammation mediated the effect of 25(OH)D3 deficiency on cognitive impairment.ResultsThere were lower plasma 25(OH)D3 concentration and higher IL-1β and IL-18 levels in the MCI group compared with the controls. The levels of 25(OH)D3 were positively correlated with the MoCA scores and scores of different domains; the levels of IL-1β and IL-18 were negatively correlated with them (p < 0.05). In multivariate logistic analysis, there were significant associations among 25(OH)D3, IL-1β, IL-18, and MCI after adjusted. Further analysis revealed the significant association between the subjects with VD deficiency and the highest quartile of IL-18 in MCI (OR = 4.066), not with IL-1β after adjusting the confounding variables in MCI group. Ultimately, mediation analysis suggested that IL-1β and IL-18 could explain 25.4 and 17.5% of effect of the risk of cognitive impairment related to 25(OH)D3 deficiency.ConclusionOur findings suggested that 25(OH)D3 deficiency could increase the risk of cognitive impairment by a mechanism partly involving inflammation. Therefore, vitamin D supplementation may improve or delay the decline in cognitive function caused by inflammation in the elderly.

Sleep quality mediates the relationship between systemic inflammation and neurocognitive performance

“…Our findings were in line with existing evidence on the positive association between peripheral levels of IL-18 and neurocognitive deficits in older adults with MCI ( Cheng et al, 2022 ) and patients with AD ( Bossù et al, 2008 ; Chen et al, 2014 ; Swardfager et al, 2010 ) and further extended it in healthy individuals. IL-18 participates in regulating several immune pathways including inflammasome activation and the development of Th1, Th2 and Th17 responses ( Harel et al, 2022 ; Sharma and Kanneganti, 2021 ).…”

“…Systemic inflammation induces neuroinflammation, together with blood-brain barrier breakdown and neuropathological protein aggregation provokes neurodegenerative changes ( Galea, 2021 ; Hoogland et al, 2015 ; Kempuraj et al, 2016 ; Perry, 2010 ). Elevated peripheral inflammatory markers (i.e., interleukin [IL]-6, IL-18 and tumour necrosis factor [TNF]-α) and a higher level of neuroinflammation have been detected in people suffering from Alzheimer's disease (AD) and mild cognitive impairment (MCI) ( Bradburn et al, 2019 ; Cheng et al, 2022 ; Darweesh et al, 2018 ; Leonardo and Fregni, 2023 ; Shen et al, 2019 ). Particularly, the T helper (Th) 1 response plays a particularly important role in maintaining systemic inflammation, which is further associated with neurocognitive deficits.…”

Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: Biological role in induction, regulation, and treatment

“…IL-18 have been shown to be a diagnostic marker and predictor of inflammatory conditions like myocardial ischemia ( 106 ), acute respiratory distress syndrome ( 107 , 108 ), chronic obstructive pulmonary disease ( 109 ), post infectious bronchiolitis obliterans ( 110 ) and sepsis-induced multi organ injury ( 111 ). IL-18 has also received increase attention in the pathophysiology of neuro-vascular diseases such as in intracerebral hemorrhage ( 112 ), Japanese encephalitis ( 113 ), ocular Behcet disease ( 114 ), abdominal aortic aneurysm ( 115 ), amyotrophic lateral sclerosis ( 116 ), glioma ( 117 ) and most interestingly in cognitive impairment ( 118 ) and agitation in severe mental disease ( 119 ).…”

Ozone Pollution, Oxidative Stress, Regulatory T Cells and Antioxidants

“…However, when there is an exacerbated accumulation of Aβ, the microglia suffer a functional deterioration that facilitates neurotoxicity [ 85 , 86 ]. Specifically in Alzheimer’s disease, it has been shown that in addition to plaques and neurofibrillary tangles, chronic neuroinflammation is the third main pathological feature of Alzheimer’s disease, and is generated by the activation of microglia cells and the release of cytokines [ 87 ] such as TNF-α, a proinflammatory cytokine, which is elevated in patients with Alzheimer’s disease [ 88 , 89 ] as well as IL-6, IL-12, and IL-18, IFN-γ, chemokine (MCP-1), and other neurotoxic agents [ 90 , 91 ]. Another characteristic observed with AD is that the percentage of Treg cells and the levels of TGF-β in the blood of patients with mild cognitive impairment is higher in relation to patients with dementia.…”