Mediators of a Physical Activity Intervention on Cognition in Breast Cancer Survivors: Evidence From a Randomized Controlled Trial

Sheri J Hartman, Lauren S Weiner, Sandahl H Nelson, Loki Natarajan, Ruth E Patterson, Barton W Palmer, Barbara A Parker, Dorothy D Sears, Sheri J Hartman, Lauren S Weiner, Sandahl H Nelson, Loki Natarajan, Ruth E Patterson, Barton W Palmer, Barbara A Parker, Dorothy D Sears

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: The objective of this secondary analysis examined physical and psychological function 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: A total of 87 sedentary breast cancer survivors were randomized to a 12-week physical activity intervention (n=43) or control condition (n=44). Objectively measured processing speed (National Institutes of Health Toolbox Oral Symbol Digit), self-reported cognition (patient-reported outcomes measurement information system [PROMIS] cognitive abilities), PROMIS measures of physical and psychological function (depression, anxiety, fatigue, and physical functioning), and plasma biomarkers (brain-derived neurotrophic factor, homeostatic model assessment 2 of insulin resistance, and C-reactive protein [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. Exploratory analyses examined self-reported cognitive abilities and processing speed as mediators of the intervention effect on physical functioning.

Results: Participants in the exercise arm had significantly greater improvements in physical functioning (beta=1.23; 95% CI 2.42 to 0.03; P=.049) and reductions in anxiety (beta=-1.50; 95% CI -0.07 to -2.94; P=.04) than those in the control arm. Anxiety significantly mediated the intervention effect on cognitive abilities (bootstrap 95% CI -1.96 to -0.06), whereas physical functioning did not (bootstrap 95% CI -1.12 to 0.10). Neither anxiety (bootstrap 95% CI -1.18 to 0.74) nor physical functioning (bootstrap 95% CI -2.34 to 0.15) mediated the intervention effect on processing speed. Of the biomarkers, only CRP had greater changes in the exercise arm than the control arm (beta=.253; 95% CI -0.04 to 0.57; P=.09), but CRP was not associated with cognition; therefore, none of the biomarker measures mediated the intervention effect on cognition. Neither cognitive abilities (bootstrap 95% CI -0.06 to 0.68) nor processing speed (bootstrap 95% CI -0.15 to 0.63) mediated the intervention effect on physical function.

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.

Trial registration: ClinicalTrials.gov NCT02332876; https://ichgcp.net/clinical-trials-registry/NCT02332876.

Keywords: anxiety; cognitive function; exercise; neoplasms.

Conflict of interest statement

Conflicts of Interest: None declared.

©Sheri J J Hartman, Lauren S Weiner, Sandahl H Nelson, Loki Natarajan, Ruth E Patterson, Barton W Palmer, Barbara A Parker, Dorothy D Sears. Originally published in JMIR Cancer (http://cancer.jmir.org), 11.10.2019.

Figures

Figure 1
Figure 1
Differences in change from baseline to 12 weeks on measures of physical and psychological function by randomization group among breast cancer survivors enrolled in a randomized controlled trial of physical activity (N=87). Estimate: estimate of difference between groups for change in quality of life scores.
Figure 2
Figure 2
Bootstrap mediation analysis of anxiety, physical functioning, and C-reactive protein self-reported cognitive abilities among breast cancer survivors enrolled in a randomized trial of physical activity (N=87). Solid arrow lines indicate a P value less than .10. Dashed arrow lines indicate a P value greater than or equal to .10.
Figure 3
Figure 3
Bootstrap mediation analysis of anxiety, physical functioning, and C-reactive protein on processing speed among breast cancer survivors enrolled in a randomized trial of physical activity (N=87). Solid arrow lines indicate a P value less than .10. Dashed arrow lines indicate a P value greater than or equal to .10.

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