Mediators of a physical activity intervention on cognition in breast cancer survivors: Evidence from a randomized controlled trial
ABSTRACT
Background:
Emerging research suggests that increasing physical activity can help improve cognition among breast cancer survivors. However, little is known about the mechanism through which physical activity impacts cancer survivors’ cognition.
Objective:
This study examined physical and psychological function and biological mechanisms potentially linking physical activity with changes in cognition among breast cancer survivors in a randomized controlled trial where the Exercise arm had greater improvements in cognition than the Control arm.
Methods:
Eighty-seven sedentary breast cancer survivors were randomized to a 12-week physical activity intervention (N=43) or control condition (N=44). Objectively-measured processing speed (NIH Toolbox Oral Symbol Digit), self-reported cognition (PROMIS Cognitive Abilities), PROMIS measures of physical and psychological function (depression, anxiety, fatigue, and physical functioning), and plasma biomarkers (BDNF, HOMA2-IR, CRP) were collected at baseline and 12 weeks. Linear mixed effects models tested intervention effects on changes in physical and psychological function variables and biomarkers. Bootstrapping was used to assess mediation.
Results:
Participants in the Exercise arm had significantly greater improvements in physical functioning (b=-1.23, 95% CI: -2.42, -0.03, p=0.049) and reductions in anxiety (b=1.50, 95% CI: 0.07, 2.94, p=0.041) vs. the Control arm. Anxiety significantly mediated the intervention effect on cognitive abilities (Bootstrap 95% CI: -1.96, -0.06), while physical functioning did not (Bootstrap 95% CI: -1.12, 0.10). Neither anxiety (Bootstrap 95% CI: -1.18, 0.74) nor physical functioning (Bootstrap 95% CI: -2.34, 0.15) mediated the intervention effect on processing speed. Of the biomarkers, only CRP had greater changes in the Exercise arm vs. Control arm (b=0.253, 95% CI: -0.04, 0.57, p=0.09), but CRP was not associated with cognition; therefore, none of the biomarker measures mediated the intervention effect on cognition.
Conclusions:
Physical activity interventions may improve self-reported cognition by decreasing anxiety. If supported by larger studies, reducing anxiety may be an important target for improving self-reported cognition among cancer survivors. Clinical Trial: ClinicalTrials.gov NCT02332876
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