Association of peripheral interleukin-6 with global cognitive decline in non-demented adults: a meta-analysis of prospective studies

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 aetiology 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 ageing 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

Activation state (CD54) of cDCs and monocytes in non frail and frail old subjects.

<p>Whole blood cells were stimulated or not with LPS or R848 during 5 h. Expression of CD54 was assessed for (A) monocytes (Lineage^–HLA-DR⁺CD11c⁺CD14⁺), (B) cDCs (Lineage⁻HLA-DR⁺CD11c⁺CD14⁻CD123⁻). MFI (mean) values for each donor are shown. The bars represent median values ± interquartile range.</p

Decreased production of IL-12p70 and IL-23 in response to LPS+R848 stimulation in frail old individuals.

<p>Whole blood cells from frail (n = 10) and non frail (n = 9) old individuals were stimulated with LPS+R848 during 18 h. IL-12p70 and IL-23 were measured in cell-free supernatants by ELISA. Each dot represents a single donor and the bars represent median values ± interquartile range. ***p<0.001.</p

Characteristics of the study group.

<p>Characteristics of the study group.</p

NF-κB p65, p38 and Erk phosphorylation of monocytes and cDCs after LPS and R848 stimulation in non frail and frail old subjects.

<p>Whole blood cells were stimulated with (A) LPS or (B) R848 for 20 minutes. MFI (mean) expression of phosphorylated NF-<b>κ</b>B p65, p38 and Erk MAPK protein in monocytes (Lineage^–HLA-DR⁺CD11c⁺CD14⁺) or cDCs (Lineage⁻HLA-DR⁺CD11c⁺CD14⁻) are shown for each donor. Bars represent median values ± interquartile range. *p<0.05.</p

Association between TLR response and frailty (N = 52) : Multivariate analyses.

<p>Association between TLR response and frailty (N = 52) : Multivariate analyses.</p

Intracellular cytokine staining of cDCs and monocytes from non frail and frail old subjects.

<p>Whole blood cells were stimulated with (A) LPS or (B) R848 during 5 h in presence of brefeldin A. Percentage of IL-6⁺, TNFα⁺ and IL-12/23p40⁺ monocytes and cDCs are shown. The bars represent median values ± interquartile range. *p<0.05.</p

Demographic, geriatric and biochemical characteristics of frail and non frail subjects >75 years of age.

<p>Demographic, geriatric and biochemical characteristics of frail and non frail subjects >75 years of age.</p