Saskia Salzmann

Background: Diseases during childhood and adolescence such as cancer or attention-deficit/hyperactivity disorder (ADHD) can have an impact on brain development and place children and adolescents at increased risk for cognitive long-term problems. Most cognitive trainings currently available have limited efficacy and show limited transfer to nontrained tasks and everyday functioning. We developed a novel intervention (Mio-Training) aiming to increase metacognitive abilities at the intersection between exercise psychology and cognitive science to strengthen the cognitive development of pediatric patients with atypical brain development in the long term. Objective: The study assesses the efficacy of the Mio-Training on the primary (metacognitive abilities) and secondary outcomes (executive functions, processing speed, and memory) before the training, immediately after the training, and at a 3-month follow-up in patients with atypical development and healthy controls. Methods: The Mio-Training stimulates metacognition through 38 digital games, which playfully teach mnemonic strategies (ie, rehearsal, chaining, and associations), present intensive verbal and visual working memory training, and motor coordination tasks. The training group will train for 5 weeks, 3 times per week, for 20 minutes. The waiting control group will receive the training after completion of the study procedure. We will evaluate the efficacy of the Mio-Training on metacognitive abilities and cognitive performance in a randomized controlled clinical trial. We expect a long-term increase in metacognitive abilities associated with an increase in subjective and objective cognitive performance. The efficacy of the Mio-Training will be investigated in 3 subgroups (patients with cancer, ADHD, and healthy controls; each group n=40; all aged 8‐16 years) using pre-intervention and post-intervention assessments. All participants will be randomly assigned to the Mio-Training or the waiting control group, stratified by age and sex. Results: This study protocol describes the study design of the randomized controlled trial evaluating the efficacy of the Mio-Training. The project is funded from October 2024 to December 2027. Recruitment for healthy controls has been completed (n=40; October 2024-August 2025), recruitment for childhood cancer survivors (n=10, 25% participants recruited) is scheduled from August 2025 to December 2027, and recruitment for participants with ADHD (n=39, 97.5% recruited) is scheduled from October 2025 to September 2026. Data analyses have not yet commenced; first results from the ADHD subgroup are expected in early 2027, with findings from the cancer survivor subgroup anticipated in early 2028 following completion of recruitment. Conclusions: To strengthen cognitive development in young patients with atypical development, it is necessary to address the current lack of effective treatment options. The combination of cognitive and motor training with metacognitive abilities may support patients’ cognitive maturation trajectories and will enable transfer of the training effect to everyday and school situations.

BACKGROUND Disease during childhood and adolescence such as cancer, or ADHD can have an impact on brain development and places children and adolescents at increased risk for cognitive long-term problems. Most cognitive trainings currently available have limited efficacy and lack a transfer to non-trained tasks and everyday functioning. We developed a novel intervention (Mio-Training) aiming to increase metacognitive abilities at the intersection between exercise psychology and cognitive science to strengthen the cognitive development of paediatric patients with atypical brain development in the long-term. OBJECTIVE The study assesses the efficacy of the Mio-Training on the primary (metacognitive abilities) and secondary outcomes (executive functions, processing speed, memory), before, immediately after the training and at 3-months follow-up in patients with atypical development and healthy controls. METHODS We will evaluate the efficacy of a newly developed cognitive training (Mio-Training) on metacognitive abilities and cognitive performance in a randomized controlled clinical trial. We expect a long-term increase in metacognitive abilities relating to an increase in subjective and objective cognitive performance. Intervention: The Mio-Training stimulates metacognition through 38 digital games, which playfully teach mnemonic strategies (i.e. rehearsal, chaining, associations), present intensive verbal and visual working memory training and motor coordination tasks. The training group will train for 5 weeks, 3 times per week for 20 minutes. The waiting control group will receive the training after termination of the study procedure. Participants: The efficacy of the Mio-Training will be investigated in three subgroups (patients with cancer, ADHD and healthy controls, each group n = 40, all aged 8-16 years) using pre- and post-intervention assessments. All participants will be randomly assigned to the Mio-Training or the waiting control group, stratified by age and sex. RESULTS This study protocol describes the study design of the randomized controlled trial evaluating the efficacy of the Mio-Training. Data collection started in August 2025 and will continue until August 2027. First results are expected to be submitted for publication in spring 2027. CONCLUSIONS To strengthen cognitive development in young patients with atypical development, it is necessary to address the current lack of effective treatment options. The combination of cognitive and motor training with metacognitive abilities may support patient’s cognitive maturation trajectory and will enable a transfer of the training effect to everyday and school situations. CLINICALTRIAL Clinicaltrials.gov (Patients with cancer and healthy controls: NCT06464237, date of registration: 12.06.2024, ADHD: NCT07162831, date of registration: 01.09.2025)

Summary: Sleep‐disordered breathing (SDB) is linked to cognitive dysfunction. Although SDB is common in stroke patients, the impact of SDB and its early treatment on cognitive functioning after stroke remains poorly investigated. Therefore, we explored the association between SDB and post‐stroke cognitive functioning, including the impact of early SDB treatment with adaptive servo‐ventilation (ASV) on cognitive recovery from acute event to 3 months post‐stroke. We used data from two studies, which included ischaemic stroke patients (n = 131) and no‐stroke controls (n = 37) without SDB (apnea–hypopnea index, AHI n = 30) versus SDB ASV‐ (n = 29) with cognitive recovery. In an exploratory subanalysis, compliant SDB ASV+ (n = 14) versus SDB ASV‐ showed improvements with ASV in visual memory and cognitive flexibility. Combining the stroke and non‐stroke datasets, SDB (n = 85) versus no‐SDB (n = 83) was associated with deficits in visual memory and response inhibition independently of stroke. SDB ASV‐ versus no‐SDB (n = 51) was associated with less improvement in visual memory. There was no substantial evidence for benefits of intention‐to‐treat ASV on cognitive recovery. Exploratory analysis indicated that compliant ASV treatment could benefit visual memory and cognitive flexibility, whereas untreated SDB could contribute to a poor recovery of visual memory.