The Brainfit study: efficacy of cognitive training and exergaming in pediatric cancer survivors - a randomized controlled trial.

BACKGROUND: Cancer survival comes at a price: pediatric cancer survivors bear a high risk for a wide range of cognitive difficulties. Therefore, interventions targeting these difficulties are required. The aim of the present clinical trial is to extend empirical evidence about efficacy of cognitive and physical training in pediatric cancer survivors. It is hypothesized that early cognitive and physical interventions affect the remediation of pediatric cancer survivors in terms of improved executive functions (primary outcome). Additional positive effects of cognitive and physical intervention to other areas such as memory and attention are expected (secondary outcome). Changes in cognitive performance are expected to be associated with structural and functional changes in the brain. METHODS: Overall, 150 pediatric cancer survivors and 50 matched controls will be included in this trial. The cancer survivors will be randomly assigned to either a computerized cognitive training, a physical training (exergaming) or a waiting control group. They will be assessed with neuropsychological tests, tests of sport motor performance and physical fitness before and after 8 weeks of training and again at a 3-months follow-up. Moreover, neuroimaging will be performed at each of the three time points to investigate the training impact on brain structure and function. DISCUSSION: With increasing cancer survival rates, evidence-based interventions are of particular importance. New insights into training-related plasticity in the developing brain will further help to develop tailored rehabilitation programs for pediatric cancer survivors. TRIAL REGISTRATION: KEK BE 196/15; KEK ZH 2015-0397; ICTRP NCT02749877 ; date of registration: 30.11.2016; date of first participant enrolment: .18.01.2017.

Motor ability, physical self-concept and health-related quality of life in pediatric cancer survivors.

BACKGROUND: Cancer survivorship is frequently associated with severe late effects. However, research into pediatric cancer survivors on late effects in motor ability, physical self-concept and their relationship to quality of life is limited. METHODS: Using multiple regression analyses, 78 pediatric cancer survivors and 56 typically developing children were compared in motor ability, physical self-concept and health-related quality of life. In addition, mediational multi-group analyses between motor ability (independent variable), physical self-concept (mediator) and quality of life (dependent variable) were calculated. RESULTS: Pediatric cancer survivors had a lower motor ability (gHedges  = 0.863), a lower physical self-concept with regard to several scales of the PSDQ-S (gHedges  = 0.318-0.764) and a higher relative risk for a below average quality of life than controls (RR = 1.44). Children with a history of cancer involving the central nervous system showed poorer motor ability compared to those without central nervous system involvement (gHedges  = 0.591). Furthermore, the physical self-concept significantly mediated the relationship between motor ability and quality of life in pediatric cancer survivors but not in typically developing children. CONCLUSIONS: Results show the importance of monitoring and supporting the development of motor ability in the aftercare of pediatric cancer survivors. Physical activity interventions may be advisable to prevent physical activity-related late effects and potentially improve related psychosocial variables such as quality of life.

The Working Memory Network and Its Association with Working Memory Performance in Survivors of non-CNS Childhood Cancer.

Childhood cancer and its treatment puts survivors at risk of low working memory capacity. Working memory represents a core cognitive function, which is crucial in daily life and academic tasks. The aim of this functional MRI (fMRI) study was to examine the working memory network of survivors of childhood cancer without central nervous system (CNS) involvement and its relation to cognitive performance. Thirty survivors (aged 7-16 years, ≥ 1 year after cancer treatment) and 30 healthy controls performed a visuospatial working memory task during MRI, including a low- and a high-demand condition. Working memory performance was assessed using standardized tests outside the scanner. When cognitive demands increased, survivors performed worse than controls and showed evidence for slightly atypical working memory-related activation. The survivor group exhibited hyperactivation in the right-hemispheric superior parietal lobe (SPL) in the high- compared to the low-demand working memory condition, while maintaining their performance levels. Hyperactivation in the right SPL coincided with poorer working memory performance outside the scanner in survivors. Even in survivors of childhood cancer without CNS involvement, we find neural markers pointing toward late effects in the cerebral working memory network.AbbreviationsfMRI: Functional magnetic resonance imaging; CNS: Central nervous system; MNI: Montreal Neurological Institute; SES: Socioeconomic status; SPL: Superior parietal lobe.

Cortical Morphometry and Its Relationship with Cognitive Functions in Children after non-CNS Cancer.

Background: Childhood cancer survivors (Ccs) are at risk for cognitive late-effects, which might result from cortical alterations, even if cancer does not affect the brain. The study aimed to examine gray and white matter volume and its relationship to cognition. Methods: Forty-three Ccs of non-central nervous system cancers and 43 healthy controls, aged 7-16 years, were examined. Cognitive functions and fine motor coordination were assessed and T1-weighted images were collected for voxel-based morphometry. Results: Executive functions (p = .024, d = .31) were poorer in Ccs than controls, however still within the normal range. The volume of the amygdala (p = .011, ŋ2 = .117) and the striatum (p = .03, ŋ2 = .102) was reduced in Ccs. No significant structure-function correlations were found, neither in patients nor controls. Conclusion: Non-CNS childhood cancer and its treatment impacts on brain structures relevant to emotion processing.

Impact of non-CNS childhood cancer on resting-state connectivity and its association with cognition.

INTRODUCTION: Non-central nervous system cancer in childhood (non-CNS CC) and its treatments pose a major threat to brain development, with implications for functional networks. Structural and functional alterations might underlie the cognitive late-effects identified in survivors of non-CNS CC. The present study evaluated resting-state functional networks and their associations with cognition in a mixed sample of non-CNS CC survivors (i.e., leukemia, lymphoma, and other non-CNS solid tumors). METHODS: Forty-three patients (off-therapy for at least 1 year and aged 7-16 years) were compared with 43 healthy controls matched for age and sex. High-resolution T1-weighted structural magnetic resonance and resting-state functional magnetic resonance imaging were acquired. Executive functions, attention, processing speed, and memory were assessed outside the scanner. RESULTS: Cognitive performance was within the normal range for both groups; however, patients after CNS-directed therapy showed lower executive functions than controls. Seed-based connectivity analyses revealed that patients exhibited stronger functional connectivity between fronto- and temporo-parietal pathways and weaker connectivity between parietal-cerebellar and temporal-occipital pathways in the right hemisphere than controls. Functional hyperconnectivity was related to weaker memory performance in the patients' group. CONCLUSION: These data suggest that even in the absence of brain tumors, non-CNS CC and its treatment can lead to persistent cerebral alterations in resting-state network connectivity.

Effects of Cognitive Training and Exergaming in Pediatric Cancer Survivors-A Randomized Clinical Trial.

PURPOSE: Although most pediatric cancer patients survive, those who undergo anticancer treatments like chemotherapy and/or radiotherapy are at a high risk for late effects, such as cognitive deficits. To counteract these deficits, feasible and effective interventions are needed. The aim of this study was to compare the effects of working memory training, exergaming, and a wait-list control condition on cognitive functions in pediatric cancer survivors. METHODS: In a parallel-group randomized trial, 69 pediatric cancer survivors aged 7-16 yr (mean = 11.35, SD = 3.53) were randomly assigned to 8-wk working memory training, exergaming, or a wait-list control group. Each training course consisted of three 45-min training sessions per week. The primary outcome comprised the core executive functions (visual working memory, inhibition, switching), and the secondary outcomes included other cognitive domains (intelligence, planning, memory, attention, processing speed), motor abilities, and parent rating on their children's executive functions. Assessments were conducted both before and immediately after the interventions, and at 3-month follow-up. RESULTS: Linear mixed models revealed that participants in the working memory training group showed a linear improvement in visual working memory after training and at follow-up compared with the control group. No other intervention effects of either type of training could be detected. CONCLUSION: This study presents evidence that working memory training improves visual working memory in pediatric cancer survivors. Results show that near-transfer, but no far-transfer effects can be expected from working memory training. Multiple-component interventions tailored to fit the individual's cognitive profile are needed to best support cognitive development after cancer and its treatment.