Predictors of cognitive decline in older individuals without dementia: An updated meta-analysis

To evaluate the effect of overall peripheral inflammatory levels on cognitive function, we explored the relationship between established biomarkers of peripheral inflammation (circulating C-reactive protein [CRP], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]) and cognitive decline by performing a review of observational studies and creating an updated summary.

We included literatures exploring the relationship between peripheral levels of CRP, IL-6, and TNF-α and subsequent cognitive decline, published until July 2022, by searching the following databases: PubMed, Embase, Web of Science, the Cochrane Library, ClinicalTrials, CNKI, and VIP databases. We used random-effects models to pool the odds ratios (ORs) for the risks of subsequent cognitive decline in older adults with high levels of peripheral inflammation. We initially screened out 501 literatures, of which only 17 were ultimately eligible. Overall, there were 19,516 older individuals included in our meta-analysis, and 2134 of them experienced subsequent cognitive change.

Individuals with high levels of peripheral inflammation may have 14% more chance to develop subsequent cognitive decline than those with low levels (OR = 1.14, 95% CI: 1.03-1.27; p < 0.00001). In the subgroup analysis, the incidence of cognitive decline was higher in individuals with high levels of IL-6. This study further demonstrates the link between systemic inflammation and cognitive status.

Detecting CRP, IL-6, and TNF-α in peripheral blood is necessary, as they may become effective indicators for forthcoming cognitive performance.