AUTHOR=Leonardo Sofia , Fregni Felipe 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=15

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1069439

DOI=10.3389/fnagi.2023.1069439

ISSN=1663-4365

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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), <italic>p</italic> &lt; 0.05], IL-1β [0.94, 95% CI (−0.04, 1.92), <italic>p</italic> &lt; 0.05], interleukin-6 (IL-6) [0.46, 95% CI (0.05, 0.88), <italic>p</italic> &lt; 0.005], TNF alpha [0.22, 95% CI (−0.24, 0.68), <italic>p</italic> &lt; 0.05], sTNFR-1 [0.74, 95% CI (0.46, 1.02), <italic>p</italic> &lt; 0.05] in AD compared to controls. Similarly, higher levels of IL-1β [0.17, 95% CI (0.05, 0.28), <italic>p</italic> &lt; 0.05], IL-6 [0.13, 95% CI (0.08, 0.18), <italic>p</italic> &lt; 0.005], TNF alpha [0.28, 95% CI (0.07, 0.49), <italic>p</italic> &lt; 0.05], sTNFR-1 [0.21, 95% CI (0.05, 0.48), <italic>p</italic> &lt; 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)].</p></sec><sec><title>Conclusion</title><p>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.</p></sec>