Cognition Is Associated With Peripheral Immune Molecules in Healthy Older Adults: A Cross-Sectional Study

Abstract

Background: Cognition in the elderly is heterogeneous. Senescence of the immune system is increasingly considered as a potential player in cognitive performance. We explored here the interplay between cognitive performance and peripheral immune molecules in healthy older individuals.

Methods: A cross-sectional study of clinically well characterized senior healthy individuals (120; 51-87 years old) previously clustered as "Good" and "Poor" performers based on established tests that evaluate memory and executive function. A plasma concentration of 30 immune molecules was assessed by multiplex analysis and correlated with parameters of cognitive performance.

Results: Participants with worse cognitive performance ("Poor") exhibited increased concentrations of IL-1β, IL-8, IL-13, and tumor necrosis factor (TNF) when compared to individuals with a better cognitive performance ("Good"). The cognitive dimensions memory and executive function, when considered separately, displayed a negative association with several immune molecules (IL-1β, IL-1RA, IL-6, IL-13, IP-10, and TNF with memory and only IL-1β with executive function), even controlling for age, sex, years of formal education, mood, and use of anti-inflammatory drugs. Regression analysis showed that several of these molecules (IL-1β, IL-6, IL-8, and IL-13) contribute to predicting whether an individual belongs to the "Good" or "Poor" cognitive performance group.

Conclusion: These results strengthen the hypothesis that increased concentrations of peripheral immune molecules, like IL-1β, are associated with worse cognitive performance in senior healthy individuals. It further highlights that some poorly studied immune molecules should be considered in the context of cognitive aging, such as IL-13, here revealed as a new player in such interaction.

Keywords: chemokines; cognition; cytokines; healthy aging; immune molecules.

FIGURE 1

Healthy senior individuals with distinct cognitive performances present differences in the concentration of peripheral immune molecules. The profile of cytokines, chemokines, and other immune molecules in the plasma of “Good” (black circles) and “Poor” (red triangles) cognitive performers. Dashed lines represent LLOQ (lower limit of quantification), and values below LLOQ were extrapolated from the standard curve. Dots represent each participant, columns represent the mean of the group, and bars the standard error of the mean (*p < 0.05, **p < 0.01).