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. 2023 Feb 6:15:1069439.
doi: 10.3389/fnagi.2023.1069439. eCollection 2023.

Association of inflammation and cognition in the elderly: A systematic review and meta-analysis

Sofia Leonardo  1 , Felipe Fregni  2
Affiliations

Association of inflammation and cognition in the elderly: A systematic review and meta-analysis

Sofia Leonardo et al. Front Aging Neurosci. .

Abstract

Background: The development of mild cognitive impairment (MCI) and Alzheimer's disease (AD) may be associated with an inflammatory process. Inflammatory cytokines may be a surrogate for systemic inflammation leading to worsening neurological function. We aim to investigate the association between cognitive impairment and inflammation by pooling and analyzing the data from previously published studies.

Methods: We performed a systematic literature search on MEDLINE, PubMed, Embase, Web of Science, and Scopus for prospective longitudinal and cross-sectional studies evaluating the relationship between inflammation and cognitive functions.

Results: A total of 79 articles were included in our systematic review and meta-analysis. Pooled estimates from cross-sectional studies have demonstrated an increased level of C-reactive protein (CRP) [Hedges's g 0.35, 95% CI (0.16, 0.55), p < 0.05], IL-1β [0.94, 95% CI (-0.04, 1.92), p < 0.05], interleukin-6 (IL-6) [0.46, 95% CI (0.05, 0.88), p < 0.005], TNF alpha [0.22, 95% CI (-0.24, 0.68), p < 0.05], sTNFR-1 [0.74, 95% CI (0.46, 1.02), p < 0.05] in AD compared to controls. Similarly, higher levels of IL-1β [0.17, 95% CI (0.05, 0.28), p < 0.05], IL-6 [0.13, 95% CI (0.08, 0.18), p < 0.005], TNF alpha [0.28, 95% CI (0.07, 0.49), p < 0.05], sTNFR-1 [0.21, 95% CI (0.05, 0.48), p < 0.05] was also observed in MCI vs. control samples. The data from longitudinal studies suggested that levels of IL-6 significantly increased the risk of cognitive decline [OR = 1.34, 95% CI (1.13, 1.56)]. However, intermediate levels of IL-6 had no significant effect on the final clinical endpoint [OR = 1.06, 95% CI (0.8, 1.32)].

Conclusion: The data from cross-sectional studies suggest a higher level of inflammatory cytokines in AD and MCI as compared to controls. Moreover, data from longitudinal studies suggest that the risk of cognitive deterioration may increase by high IL-6 levels. According to our analysis, CRP, antichymotrypsin (ACT), Albumin, and tumor necrosis factor (TNF) alpha may not be good surrogates for neurological degeneration over time.

Keywords: CRP; IL-6; cognition; cytokines; elderly; inflammation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.
FIGURE 2
FIGURE 2
Forest plot of pooled Hedge’s g depicting high C-reactive protein (CRP) concentration in Alzheimer’s disease (AD) samples compared to controls.
FIGURE 3
FIGURE 3
Forest plot of pooled Hedge’s g depicting high IL-1β concentration in Alzheimer’s disease (AD) samples compared to controls.
FIGURE 4
FIGURE 4
Forest plot of pooled Hedge’s g depicting high IL-6 concentration in Alzheimer’s disease (AD) samples compared to controls.
FIGURE 5
FIGURE 5
Forest plot of pooled Hedge’s g depicting high tumor necrosis factor (TNF)-alpha concentration in Alzheimer’s disease (AD) samples compared to controls.
FIGURE 6
FIGURE 6
Forest plot of pooled Hedge’s g depicting high sTNFR-1 concentration in Alzheimer’s disease (AD) samples compared to controls.
FIGURE 7
FIGURE 7
Forest plot of pooled Hedge’s g depicting high IL-1β concentration in mild cognitive impairment (MCI) samples compared to controls.
FIGURE 8
FIGURE 8
Forest plot of pooled Hedge’s g depicting high IL-6 concentration in mild cognitive impairment (MCI) samples compared to controls.
FIGURE 9
FIGURE 9
Forest plot of pooled Hedge’s g depicting high tumor necrosis factor (TNF)-alpha concentration in mild cognitive impairment (MCI) samples compared to controls.
FIGURE 10
FIGURE 10
Forest plot of pooled Hedge’s g depicting high C-reactive protein (CRP) concentration in mild cognitive impairment (MCI) samples compared to controls.
FIGURE 11
FIGURE 11
(A) Forest plot of pooled odds ratio (OR) for interleukin-6 (IL-6) high concentration and cognitive decline. (B) Forest plot of pooled odds ratio (OR) for IL-6 intermediate concentration and cognitive decline. (C) Forest plot of pooled odds ratio (OR) for C-reactive protein (CRP) high concentration and cognitive decline. (D) Forest plot of pooled odds ratio (OR) for CRP intermediate concentration and cognitive decline.
FIGURE 12
FIGURE 12
(A) Forest plot of pooled odds ratio (OR) for antichymotrypsin (ACT), albumin, tumor necrosis factor (TNF), and cognitive decline. (B) Funnel plot for the included longitudinal studies for interleukin-6 (IL-6) levels (intermediate and high).
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