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. 2018 Jan 8:9:438.
doi: 10.3389/fnagi.2017.00438. eCollection 2017.

Association of Peripheral Interleukin-6 with Global Cognitive Decline in Non-demented Adults: A Meta-Analysis of Prospective Studies

Steven Bradburn  1 , Jane Sarginson  1   2 , Christopher A Murgatroyd  1
Affiliations

Association of Peripheral Interleukin-6 with Global Cognitive Decline in Non-demented Adults: A Meta-Analysis of Prospective Studies

Steven Bradburn et al. Front Aging Neurosci. .

Abstract

Background: Elevated biomarkers of systemic inflammation have been reported in individuals with cognitive decline, however, most of the literature concerns cross-sectional analyses that have produced mixed results. This study investigates the etiology of this association by performing meta-analyses on prospective studies investigating the relationship between baseline interleukin-6 (IL-6), an established marker of peripheral inflammation, with cognitive decline risk in non-demented adults at follow-up. Methods: We reviewed studies reporting peripheral IL-6 with future cognitive decline, up to February 2017 by searching the PubMed, Science Direct, Scopus and Google Scholar databases. Studies which contained odds ratios (ORs) for the association between circulating baseline IL-6 and longitudinal cognitive performance in non-demented community dwelling older adults were pooled in random-effects models. Results: The literature search retrieved 5,642 potential articles, of which 7 articles containing 8 independent aging cohorts were eligible for review. Collectively, these studies included 15,828 participants at baseline. Those with high circulating IL-6 were 1.42 times more likely to experience global cognitive decline at follow-up, over a 2-7-year period, compared to those with low IL-6 (OR 1.42, 95% CI 1.18-1.70; p < 0.001). Subgroup and sensitivity analyses suggests that this association is independent of the study sample size, duration of follow-up and cognitive assessments used. Conclusions: These results add further evidence for the association between high peripheral inflammation, as measured by blood IL-6, and global cognitive decline. Measuring circulating IL-6 may be a useful indication for future cognitive health.

Keywords: cognitive aging; cognitive decline; inflammaging; inflammation; interleukin-6; longitudinal studies; meta-analysis; prospective studies.

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Figures

Figure 1
Figure 1
Flowchart summarizing the literature search for the meta-analysis.
Figure 2
Figure 2
Forest plot for the association between high (A) and intermediate (B) peripheral levels of interleukin-6 and future global cognitive decline analysis.
Figure 3
Figure 3
Begg's funnel plots for the association between high (A) and intermediate (B) peripheral levels of interleukin-6 and future global cognitive decline analysis. Funnel plot displays the log(odds ratio) against the standard error, with the pooled effect (solid line) and pseudo 95% confidence limits (dashed lines).
See this image and copyright information in PMC

References

    1. Agorastos A., Hauger R. L., Barkauskas D. A., Moeller-Bertram T., Clopton P. L., Haji U., et al. (2014). Circadian rhythmicity, variability and correlation of interleukin-6 levels in plasma and cerebrospinal fluid of healthy men. Psychoneuroendocrinology 44, 71–82. 10.1016/j.psyneuen.2014.02.020 - DOI - PubMed
    1. Banks W. A., Kastin A. J., Gutierrez E. G. (1994). Penetration of interleukin-6 across the murine blood-brain barrier. Neurosci. Lett. 179, 53–56. 10.1016/0304-3940(94)90933-4 - DOI - PubMed
    1. Charles B. A., Doumatey A., Huang H., Zhou J., Chen G., Shriner D., et al. (2011). The Roles of IL-6, IL-10, and IL-1RA in obesity and insulin resistance in African-Americans. J. Clin. Endocrinol. Metab. 96, E2018–E2022. 10.1210/jc.2011-1497 - DOI - PMC - PubMed
    1. Chen G., Castro W. L., Chow H. H., Reichlin S. (1997). Clearance of 125I-labeled interleukin-6 from brain into blood following intracerebroventricular injection in rats. Endocrinology 138, 4830–4836. 10.1210/endo.138.11.5533 - DOI - PubMed
    1. Compté N., Boudjeltia K. Z., Vanhaeverbeek M., De B., Pepersack T., Tassignon J., et al. (2013). Increased basal and alum-induced interleukin-6 levels in geriatric patients are associated with cardiovascular morbidity. PLoS ONE 8:e81911. 10.1371/journal.pone.0081911 - DOI - PMC - PubMed