Preliminary effects of a four-month circuit training intervention on cognitive function and exploratory plasma proteomic profiles in middle-aged and older women: an open-label randomized controlled trial
Frontiers in Sports and Active Living, 2026
Soga K., Takahashi M., Oba K., Uno A., Kawamura T., Kawashima K., Shinada T., Taki Y.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology Aging | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
Background
Although exercise can help prevent age-related cognitive decline, the mechanisms underlying its effects on cognition, immune function remain unclear. Therefore, this study comprehensively examined the effects of circuit training on cognitive function, and the plasma proteome in middle-aged to older women.
Methods
Forty-eight women were assigned to either a four-month circuit training program ( n = 23, exercising more than twice per week) or control group ( n = 25). Cognitive function was assessed using Stroop, Flanker, N-back, and source memory tasks. Statistical analyses were performed using linear mixed-effects models with Type III analysis of variance. The plasma proteome was measured using Olink technology (1,098 proteins). Proteomic patterns were explored using orthogonal partial least squares discriminant analysis (OPLS-DA). Furthermore, between-group comparisons of protein changes (post-baseline differences) were performed using unpaired t -tests. For functional annotation, significantly altered proteins (identified by volcano plot analysis) were subjected to pathway enrichment analyses.
Results
Within-group changes in Stroop interference and d-prime were observed in the circuit training intervention group. Furthermore, the proteins significantly elevated in the exercise intervention group were functionally categorized into anti-inflammatory and immunosuppressive pathways (LRRC25, IL10RA), angiogenesis and tissue remodeling (PROK1, TNFRSF12A), and immune cell activation (CD7). However, no protein–cognition associations remained significant after FDR correction.
Conclusions
This open-label randomized controlled trial provides preliminary evidence that a 4-month circuit training intervention may improve selected cognitive outcomes and alter circulating proteins related to immune, inflammatory, and carbohydrate-binding functions in middle-aged and older women. However, protein–cognition associations did not remain significant after FDR correction. These findings should be interpreted as hypothesis-generating and require confirmation in larger studies with integrated cognitive and molecular analyses.