Editorial: Physical activity and cancer-associated cognitive change

modes of physical activity, 2) when and for whom physical activity may have the greatest cognitive benefit, and 3) neural mechanisms of cognitive improvement through physical activity.This Research Topic illustrates that efforts to examine modes besides aerobic physical activity (which is most often investigated 20 ) are increasing, as three of the seven studies examined mind-body or meditative movement exercise interventions (n=2 yoga, n=1 Tai Chi and Qigong; most breast cancer survivors). [21][22][23] Results suggest mind-body exercise may provide a promising approach for improving self-reported cognition among cancer survivors. However, the extent to which mind-body exercise, especially lighter intensity approaches, can elicit meaningful improvements in cognitive performance is unclear, as limited to no benefit was observed in performance on cognitive tasks. Further, all three studies were preliminary or exploratory, delivered interventions of only 8-12 weeks in duration, and utilized heterogeneous methodologies to measure cognition. Consistent with previous systematic reviews of yoga interventions for mitigating CACD, 24,25 this reinforces the need for more rigorous trials in this area, in addition to common measurement approaches to improve homogeneity of methodologies.Findings of the mind-body studies are similar to cross-sectional results in women prescribed chemotherapy and/or hormonal therapy for breast cancer as reported by Hartman and colleagues. 26 Positive associations were observed between average daily minutes of moderate-tovigorous physical activity and self-reported cognitive abilities, but there was no association with cognitive performance. These results are also consistent with data from early fully-powered trials in which investigators observed improvements in self-reported cognition in exercise groups compared to control, but no differential improvement in cognitive performance. 16,19 Despite limited primary findings, results from Hartman and colleagues 26 provide insight on when and for whom physical activity may be most beneficial. Associations between physical activity and cognitive performance did not differ based upon treatments received (chemotherapy vs. hormonal therapy vs. both); however, greater physical activity was associated with better processing speed performance in survivors <2 years from diagnosis. These findings are generally consistent with previous studies indicating exercise improves processing speed in subsets of breast cancer survivors, including those who are <2 years from diagnosis, 27 prescribed endocrine therapy, 16,18 or report high fatigue burden. 16 Taken together, this evidence suggests self-report cognition and processing speed performance may be amenable to exercise in breast cancer survivorship. However, it is also possible these outcomes may be more sensitive to change and/or indicative of other health outcomes known to improve with exercise (e.g., depression, quality of life). As such, investigators should continue to utilize comprehensive batteries targeting multiple cognitive domains and consistent with International Cognition and Cancer Task Force (ICCTF) recommendations. 28 Salerno and colleagues 29 describe one of the few exercise programs designed to intervene upon cognitive function early in the cancer care continuum, 19 and results will contribute preliminary information on aerobic exercise during neoadjuvant or adjuvant chemotherapy for breast cancer, in addition to data on implementation of exercise programming during this period.This study may also provide insights into which patients may benefit most from an exercise intervention. Still, more research is needed, as these efforts represent very early progress on moderators (i.e., timing of intervention relative to cancer diagnosis and care) of exercise's cognitive benefits. There are myriad additional potential moderators proposed in the literature, spanning genetic, behavioral, functional, psychosocial, clinical, demographic, and contextual factors. 4,[30][31][32] Investigations of mechanisms of how physical activity can improve CACD are also necessary to advance the design of exercise and physical activity interventions to support cognitive health in cancer populations. Two studies in this Research Topic are among the few to examine neural outcomes associated with exercise in cancer survivors. Lesnovskaya and colleagues 33 reported positive, cross-sectional relationships between baseline cardiorespiratory fitness and resting-state functional connectivity (rsFC) in breast cancer survivors enrolled in a randomized controlled exercise trial. Page and colleagues, 34 in a pilot randomized exercise trial in breast cancer survivors, observed small to moderate improvements in brain network modularity, a measure of functional brain organization and a particularly novel rsFC metric for investigation in exercise studies, among women randomized to 12 weeks of aerobic exercise. 35 Importantly, these studies address neuroimaging outcomes recommended by ICCTF; 36 however, it is important to note the preliminary nature of the evidence and need for larger studies on exercise and brain structure and function. 17 Further, consistent with the other studies in this Research Topic, no associations between exercise-related or neural metrics and cognitive performance were observed in either study.Findings across studies raise additional considerations around conceptualization of selfreported cognition versus objectively-measured cognitive performance. Both are important metrics, as previous research suggests self-report may tap into day-to-day cognitive performance 37 and recognizes the subjective experience and well-being of cancer survivors who report attention and concentration difficulties. However, it is critical that researchers studying the cognitive and neural impacts of physical activity acknowledge conceptual independence of cognitive function as measured by self-report versus cognitive testing. 38 It is well-documented that self-reported cognition may have stronger association with psychological perceptions than with behavioral performance. 39,40 The effects of physical activity may also be different, and activity prescriptions with evidence of benefit for psychological function (e.g., depression, anxiety, mental fatigue) may more likely elicit improvements in self-reported cognition. In the present studies, authors failed to observe associations between activity-related outcomes and cognitive performance; 26,33,34 yet, associations with self-reported cognition were consistently observed. Further, improvements in self-reported anxiety and depression in breast cancer survivors were observed with Tai Chi or Qigong (along with improvements in subjective cognition), 23 and qualitative interviews with yoga participants indicated perceived benefits to mental well-being and stress. 21 These findings raise questions on whether the benefits observed reflect cognitive function, psychological function, or both.In conclusion, while these studies demonstrate progress in the evidence base on physical activity and CACD, major gaps remain. More research with the following characteristics is needed: 1) high-quality trials with adequate sample sizes and long-term follow-up; 2) survivor populations other than breast cancer; 3) racially and ethnically diverse samples; 4) rigorous methodologies consistent with expert recommendations 28,36 and assessing cognitive function as a primary outcome; 5) trials that focus on physical activity and cognition earlier in the cancer care continuum; 6) tests of modalities beyond moderate-intensity aerobic exercise; 7) investigations of dose-response; 8) analyses of moderators and mechanisms driving relationships between physical activity and cognition; and 9) study designs that provide the opportunity to examine efficacy and effectiveness, while characterizing implementation in real-world settings. 41

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