BackgroundApplying digital health technologies (DHTs) for health promotion and disease prevention is recommended by official bodies such as the World Health Organization. User-centered co-design with systematic patient and public involvement is considered best practice for developing such complex interventions. Although well-established methodological guides and frameworks are available, an important gap is that they are either holistic but generic, offering minimal operational guidance, or context-specific and operational, but focusing only on subphases of establishing DHT-enhanced interventions. ObjectiveThis paper presents a unifying consensus-based methodological guideline directed toward multidisciplinary expert teams coordinating projects on individually tailored DHTs. It delineates best practices with operational guidance for each step along the full lifecycle of DHT-enhanced training and rehabilitation concepts—from contextualization, through codevelopment, and evaluation to implementation. MethodsThe Co-Develop-IT guideline was cocreated through a structured expert consensus process that integrated, refined, and expanded on well-established existing guides and frameworks to delineate holistic and context-specific, yet flexible enough, best practices. The process consisted of biweekly 90-minute hybrid meetings between August 2024 and February 2025, in combination with written elaboration, feedback, and revisions between meetings to gradually develop a consensus on best practice recommendations. ResultsThe Co-Develop-IT guideline consists of 8 iterative phases. It is applicable to any type of end users, exercise types, intended contexts of use (eg, primary health care, community health services, and telemedicine), and overarching goals (eg, health promotion and primary through tertiary disease prevention, including rehabilitation). The Co-Develop-IT guideline introduces 5 distinct preparatory contextual research phases preceding generative codevelopment. These phases are dedicated to the structured establishment of a more robust foundation to better tailor and steer codevelopment efforts toward successful implementation. In 2 application examples, we provide proof of concept that the resulting guideline fulfills its primary purpose of providing comprehensive, context-specific, and operational, yet flexible enough best practice recommendations. ConclusionsThe unifying Co-Develop-IT guideline provides comprehensive best practices with actionable operational guidance for establishing an appropriate balance between scientific theories and frameworks and the real-world needs of interest-holders in the establishment of individually tailored DHT-enhanced training and rehabilitation concepts. Applying Co-Develop-IT contributes to overcoming the lingering evidence-to-practice gap by consistently establishing a shared mission with relevant interest-holders and ensuring that all codevelopment steps are directed toward addressing an unmet need in (clinical) practice—ultimately promoting the practical application and impact of purpose-developed DHTs.

Exergame-based training is emerging as the most effective exercise modality for improving cognition, yet its neural correlates remain largely unexplored. This study explored gray matter (GM) and white matter (WM) changes following the addition of ‘Brain-IT’ training to usual care in mild neurocognitive disorder (mNCD) and their associations with cognitive performance changes. We included 41 participants with mNCD, randomized to either the intervention (‘Brain-IT’ training + usual care) or the control (usual care only) group. ‘Brain-IT’ is a holistic, individually tailored “exercise as medicine” program for secondary mNCD prevention delivered through serious exergames. T1-weighted and diffusion tensor imaging data were analyzed via standard neuroimaging analysis pipelines (FreeSurfer, tract-based spatial statistics) to assess GM/WM volumes in predefined regions of interest and WM integrity at the voxel-to-voxel level. Intervention-related changes were explored via analyses of covariance, focusing on effect size estimates. One-sided bivariate correlation analyses explored associations between changes in brain structure and cognitive performance. Complete datasets from 30 study participants (72.0 ± 8.6 years; 27 https://clinicaltrials.gov/ct2/show/NCT05387057 .

Applying innovations in digital health technologies, such as exergames, has been recommended by official bodies like the World Health Organization for health promotion and disease prevention across various populations and age groups. Given a key advantage of interactive and gamified digital health technologies is promoting user engagement, a substantial proportion of studies have implemented recreational exergames - games primarily designed to make specific activities more fun and entertaining. In this article, we aim to move beyond the benefits of "just" providing a more engaging environment for physical and motor-cognitive activities/exercises by shedding light on serious exergame features that enhance the ecological validity of exercises and offer unique advantages for tailoring interventions beyond conventional approaches. To this end, we review the roles and mechanisms of specific exergame features in supporting adherence to relevant behavior change, neuroscience, and exercise science principles, and integrate our findings into the 'Beyond "Just" Fun of Exergames Framework'. This framework (i) implements a definition and classification approach to harmonize and provide more nuanced terminology for specific application scenarios of exergame technologies, and (ii) delineates best practices for the theoretically grounded selection and implementation of exergame features in health promotion and primary through tertiary disease prevention (including rehabilitation). By introducing this framework, we aim to support a paradigm shift by guiding game designers, researchers, and exercise and therapy practitioners from entertainment-centered recreational solutions towards serious exergames that are purposefully designed with adequate theoretical underpinnings, thereby unlocking the full potential of exergame-enhanced interventions for individuals and public health needs.

Research on physical activity (PA) and health has a fundamental concern with dose–response relationships. The variables of (1) Frequency, (2) Intensity, (3) Time, and (4) Type (i.e., the FITT principle) have traditionally been used to operationalize the dosage of PA. We consider some limitations of FITT and propose that it can be complemented by the additional variable density (from the German exercise and training variable Belastungsdichte), which can be defined as the timing of successive work bouts within a single PA bout as well as the timing between successive PA bouts within a specific time period; it does so by quantifying the temporal intervals between successive work or PA bouts (i.e., time spent at a lower PA intensity or resting such as in napping/sleeping or sedentary behaviors). Using the field of PA and brain health as an example, we discuss the opportunities and challenges for further research employing the variable density and consider its potential to improve the understanding of dose–response relationships between PA and health outcomes.

BackgroundExergame-based training enhances physical and cognitive performance in older adults, including those with mild neurocognitive disorder (mNCD). In-game metrics generated from user interactions with exergames enable individualized adjustments. However, there is a need to systematically investigate how well such game metrics capture true cognitive and motor-cognitive performance to provide a more robust basis for personalized training. ObjectiveThe primary objective was to identify valid game metrics as indicators for in-game domain-specific cognitive performance during exergaming in individuals with mNCD. We also aimed to explore game metric performance changes over time during exergame-based training. MethodsData were analyzed from individuals with mNCD who completed a 12-week home-based, exergame-based intervention following the Brain-IT training concept. A cross-sectional analysis was conducted by correlating game metrics with standardized neurocognitive reference assessments. To confirm the alternative hypothesis, we predetermined the following criteria: (1) statistically significant correlation (P≤.05; uncorrected; 1-sided) with (2) a correlation coefficient (Pearson r or Spearman ρ) of ≥0.4. Visual and curve-fitting longitudinal analyses were conducted to explore game performance changes over time. ResultsData were available from 31 participants (mean age 76.4, SD 7.5 y; n=9, 29% female). In total, 33% (6/18) of the game metrics were identified as valid indicators for in-game cognitive performance during exergaming. In the neurocognitive domain of learning and memory, these metrics included the mean reaction time (ρ=–0.747), the number of collected items (ρ=0.691), and the precision score (r=–0.607) for the game Shopping Tour (P<.001 in all cases), as well as the point rate (P=.008; r=0.471) for the game Simon. In addition, point rate was a valid indicator for executive function (P=.006; r=0.455) and visuospatial skills (P=.02; r=0.474) for the games Targets and Gears, respectively. The exploratory longitudinal analysis revealed high interindividual variability, with a general trend of the expected typical curvilinear curves of rapid initial improvements followed by a plateau in performance. ConclusionsThis study demonstrated that metrics reflecting the precision of responses generally performed better than metrics reflecting the speed of responses. These observations highlight the importance of selecting valid game metrics for implementation in exergame designs. Further research is needed to explore the potential of game metrics and identify factors contributing to individual variability in in-game performance and performance progression, as well as identifying and adopting strategies that facilitate individual learning success and thus promote effectiveness in improving health outcomes.

BackgroundCoping with residual cognitive and gait impairments is a prominent unmet need in community-dwelling chronic stroke survivors. Motor-cognitive exergames may be promising to address this unmet need. However, many studies have so far implemented motor-cognitive exergame interventions in an unstructured manner and suitable application protocols remain yet unclear. We, therefore, aimed to summarize existing literature on this topic, and developed a training concept for motor-cognitive exergame interventions in chronic stroke.MethodsThe development of the training concept for personalized motor-cognitive exergame training for stroke (PEMOCS) followed Theory Derivation procedures. This comprised (1.1) a thorough (narrative) literature search on long-term stroke rehabilitation; (1.2) a wider literature search beyond the topic of interest to identify analogies, and to induce creativity; (2) the identification of parent theories; (3) the adoption of suitable content or structure of the main parent theory; and (4) the induction of modifications to adapt it to the new field of interest. We also considered several aspects of the “Framework for Developing and Evaluating Complex Interventions” by the Medical Research Council. Specifically, a feasibility study was conducted, and refining actions based on the findings were performed.ResultsA training concept for improving cognitive functions and gait in community-dwelling chronic stroke survivors should consider the principles for neuroplasticity, (motor) skill learning, and training. We suggest using a step-based exergame training for at least 12 weeks, 2–3 times a week for approximately 45 min. Gentile's Taxonomy for Motor Learning was identified as suitable fundament for the personalized progression and variability rules, and extended by a third cognitive dimension. Concepts and models from related fields inspired further additions and modifications to the concept.ConclusionWe propose the PEMOCS concept for improving cognitive functioning and gait in community-dwelling chronic stroke survivors, which serves as a guide for structuring and implementing motor-cognitive exergame interventions. Future research should focus on developing objective performance parameters that enable personalized progression independent of the chosen exergame type.

BackgroundMild neurocognitive disorder (mNCD) is recognized as an early stage of dementia and is gaining attention as a significant healthcare problem due to current demographic changes and increasing numbers of patients. Timely detection of mNCD provides an opportunity for early interventions that can potentially slow down or prevent cognitive decline. Heart rate variability (HRV) may be a promising measure, as it has been shown to be sensitive to cognitive impairment. However, there is currently no evidence regarding the diagnostic accuracy of HRV measurements in the context of the mNCD population. This study aimed to evaluate the diagnostic accuracy of vagally-mediated HRV (vm-HRV) as a screening tool for mNCD and to investigate the relationship between vm-HRV with executive functioning and depression in older adults who have mNCD.MethodsWe retrospectively analyzed data from healthy older adults (HOA) and individuals with a clinical diagnosis of mNCD with a biomarker-supported characterization of the etiology of mNCD. Diagnostic accuracy was evaluated using receiver operating characteristic curve analysis based on the area under the curve. Sensitivity and specificity were calculated based on the optimal threshold provided by Youden’s Index. Multiple linear regression analyses were conducted to investigate the relationship between vm-HRV and executive functioning and depression.ResultsThis analysis included 42 HOA and 29 individuals with mNCD. The relative power of high frequency was found to be increased in individuals with mNCD. The greatest AUC calculated was 0.68 (with 95% CI: 0.56, 0.81) for the relative power of high frequency. AUCs for other vm-HRV parameters were between 0.53 and 0.61. No consistent correlations were found between vm-HRV and executive functioning or depression.ConclusionIt appears that vm-HRV parameters alone are insufficient to reliably distinguish between HOA and older adults with mNCD. Additionally, the relationship between vm-HRV and executive functioning remains unclear and requires further investigation. Prospective studies that encompass a broad range of neurocognitive disorders, HRV measurements, neuroimaging, and multimodal approaches that consider a variety of functional domains affected in mNCD are warranted to further investigate the potential of vm-HRV as part of a multimodal screening tool for mNCD. These multimodal measures have the potential to improve the early detection of mNCD in the future.

Introduction A collaborative international guideline recommends physical exercise (PE) for the secondary prevention of mild neurocognitive disorder (mNCD; Veronese et al., 2023). PE is proposed to promote brain plasticity, maintain or increase cognitive reserve, and alleviate the pathological state in individuals with mNCD, which is characterized by an abnormal accumulation of proteins, excessive oxidative stress, metabolic disorder, and neuroinflammation within the brain (Lu et al., 2023). Individuals with mNCD often also have disrupted self-regulatory capacity to flexibly adapt to daily life challenges. This capacity is supported by the central autonomic network (CAN), which can be viewed as an integrated component of an internal regulatory system in which the brain controls visceromotor, neuroendocrine, and behavioral responses that are critical for goal-directed behavior, adaptability, and health (Thayer, 2009). To maximize the effectiveness of secondary prevention of mNCD, interventions should be designed to also target this network specifically. This could be achieved by combining motor-cognitive training with resonance breathing guided by heart rate variability biofeedback (HRV-BF). HRV-BF training aims to increase cardiac autonomic control, enhance homeostatic regulation, and regulate emotional state. It is effective in improving cardiac autonomic control, cognitive functioning (in particular executive functions), and emotional regulation (i.e., by decreasing symptoms of depression, anxiety, and stress) across different age groups and clinical populations (Laborde et al., 2022; Lehrer et al., 2020). Evidence also supports a causal role of cardiac autonomic control in modulating plasma Alzheimer’s disease-related biomarkers (Min et al., 2023). Although HRV-BF has been suggested as a complementary treatment (Lehrer et al., 2020), its combination with motor-cognitive training remains to be investigated. Methods We systematically designed, developed, and evaluated a novel training concept (called ‘Brain-IT’) specifically for older adults with mNCD. It addresses the mechanism of action described above. The projects’ methodology (Manser & de Bruin, 2021) followed the guidelines of the Medical Research Council for the development and evaluation of complex interventions as well as the Multidisciplinary Iterative Design of Exergames (MIDE) - Framework. The Brain-IT project was structured in three phases. In phase 1, we systematically combined a comprehensive literature synthesis (Manser & de Bruin, 2021) with qualitative research including primary end users (older adults with mNCD), secondary end users (physiotherapists, occupational therapists, healthcare professionals), exergaming researchers, as well as experts from the exergaming industry (Manser et al., 2023) to specify a set of design requirements for the Brain-IT training concept. In phase 2, possible concepts were co-designed and elaborated based on the set of design requirements defined in phase 1. The first prototype of the resulting Brain-IT training concept (Manser & de Bruin, 2021) then entered the iterative cycle of feasibility, usability, safety, and acceptance testing and integrating study results for further development based on co-design until an "acceptable" solution was achieved. In this regard, we conducted a pilot randomized controlled study (RCT) including 18 individuals with mNCD. (Manser et al., 2023) Finally, in phase 3, the effectiveness of the addition of the Brain-IT training to usual care to improve global cognitive functioning is investigated in a RCT including 41 individuals with mNCD (study protocol: Manser et al., 2023). As secondary objectives, the effects of the Brain-IT training on: (1) domain-specific cognitive functioning, (2) spatiotemporal parameters of gait, (3) instrumental activities of daily living and (4) psychosocial factors (i.e. quality of life, and levels of depression, anxiety, and stress), and (5) cardiac vagal modulation are explored. Additionally, brain structure and function is evaluated by magnetic resonance imaging to explore underlying neural changes of the training in relation to adaptations in cognitive performance. Results Ten secondary end users, exergaming researchers, and experts from the exergaming industry (80% females) and eight older adults with mNCD (38% females) contributed to the qualitative research (Manser et al., 2023) which allowed us to successfully integrate all the acquired knowledge of phase 1 to determine a set of design requirements (Manser & de Bruin, 2021). This set of design requirements built the basis for phase 2, where we developed a first prototype of the Brain-IT training concept. Our reflections on the design considerations and our proposed solutions are summarized in (Manser & de Bruin, 2021; Manser et al., 2023). The Brain-IT training concept represents a guideline for applying a combination of exergame-based motor-cognitive training and HRV-BF training by standardizing the training characteristics as well as the structure and content of training and can be implemented with different hardware and software solutions. For an overview, the Brain-IT training consists of a personalized and individually adapted multi-domain exergame-based simultaneous motor–cognitive training with incorporated cognitive tasks combined with HRV-BF training. It is adopted with a deficit-oriented focus on the neurocognitive domains of (1) learning and memory, (2) executive function, (3) complex attention, and (4) visuospatial skills. Each participant is instructed to train ≥ 5x/week for ≥ 24 min per session resulting in a weekly training volume of ≥120 min. All training sessions are planned to take place at participants’ homes. In this project, we used technology of Dividat AG, Polar, and Kubios Oy to implement our training concept. In the pilot RCT we showed that Brain-IT training is feasible (mean adherence and compliance rates of 85.0 and 84.1%, respectively) and usable (mean system usability scale = 71.7 ± 15.4). In addition, high levels of exergame enjoyment, an increase in exergame enjoyment, and internalization of training motivation with large effect sizes (p = 0.03, r = 0.75 and p = 0.03, r = 0.74, respectively), as well as acceptable perceived usefulness were observed. Phase 3 is ongoing. To date, 41 participants were included into the study, of which two withdrew consent before pre-measurements, two dropped-out during intervention (one in each group), and 29 (72.6 ± 9.3 years; 24.1% females) successfully completed the study. Preliminary data suggest significant effects with large effects sizes in favor of the intervention group for global cognitive functioning (F(1, 29) = 4.692, p = 0.039, partial η2 = 0.153) as well as immediate (F(1, 29) = 6.501, p = 0.018, partial η2 = 0.213) and delayed (F(1, 29) = 5.227, p = 0.031, partial η2 = 0.179) verbal recall. The remaining (underpowered) statistical analyses revealed no significant effects, but favorable changes in descriptive statistics with small to moderate effects in favor of the intervention group, especially with regards to quality of life. Discussion/Conclusion The development of novel (exergame-based) training concepts is greatly facilitated when it is based on a theoretical framework. Applying the MIDE-framework resulted in a structured, iterative, and evidence-based approach that led to the identification of multiple key requirements for the exergame design as well as the training components that otherwise may have been overlooked or neglected. This resulted in a user-centered, personalized, and highly innovative training concept that is feasible, usable, and highly accepted by individuals with mNCD. Preliminary data regarding the effectiveness of the intervention is promising, suggesting that the training significantly improved global cognitive functioning, verbal immediate, and delayed recall with large effect sizes, and tends to be beneficial in improving quality of life. To be able to conclude about the effectiveness of the Brain-IT training concept, a full-scale confirmatory randomized controlled superiority trial is warranted. References Laborde, S., Aelle, M. S., Borges, U., Dosseville, F., Hosang, T. J., Iskra, M., Mosley, E., Salvotti, C., Spolverator, L., Zammit, N., & Javelle, F. (2022). Effects of voluntary slow breathing on heart rate and heart rate variability: A systematic review and a meta-analysis. Neuroscience & Biobehavioral Reviews, 138, Article 104711. https://doi.org/10.1016/j.neubiorev.2022.104711 Lehrer, P., Kaur, K., Sharma, A., Shah, K., Huseby, R., Bhavsar, J., Sgobba, P., & Zhang, Y. (2020). Heart rate variability biofeedback improves emotional and physical health and performance: A systematic review and meta analysis. Applied psychophysiology and biofeedback, 45(3), 109-129. https://doi.org/10.1007/s10484-020-09466-z Lu, Y., Bu, F.-Q., Wang, F., Liu, L., Zhang, S., Wang, G., & Hu, X.-Y. (2023). Recent advances on the molecular mechanisms of exercise-induced improvements of cognitive dysfunction. Translational Neurodegeneration, 12(1), 9. https://doi.org/10.1186/s40035-023-00341-5 Manser, P., Adcock-Omlin, M., & de Bruin, E. D. (2023). Design considerations for an exergame-based training intervention for older adults with mild neurocognitive disorder: Qualitative study including focus groups with experts and health care professionals and individual semistructured in-depth patient interviews. JMIR Serious Games, 11, Article e37616. https://doi.org/10.2196/37616 Manser, P., & de Bruin, E. D. (2021). Making the best out of it: Design and development of exergames for older adults with mild neurocognitive disorder - A methodological paper . Front in Aging Neuroscience, 13, Article 734012. https://doi.org/10.3389/fnagi.2021.734012 Manser, P., Michels, L., Schmidt, A., Barinka, F., & de Bruin, E. D. (2023). Effectiveness of an individualized exergame-based motor-cognitive Training concept targeted to improve cognitive functioning in older adults with mild neurocognitive disorder: Study protocol for a randomized controlled trial. JMIR Resarch Protocols, 12, Article e41173. https://doi.org/10.2196/41173 Manser, P., Poikonen, A., & de Bruin, E. D. (2023). Feasibility, usability, and acceptance of “Brain-IT”—A newly developed exergame-based training concept for the secondary prevention of mild neurocognitive disorder: A pilot randomized controlled trial [Original Research]. Frontiers in Aging Neuroscience, 15, Article 1163388. https://doi.org/10.3389/fnagi.2023.1163388 Min, J., Rouanet, J., Martini, A. C., Nashiro, K., Yoo, H. J., Porat, S., Cho, C., Wan, J., Cole, S. W., Head, E., Nation, D. A., Thayer, J. F. & Mather, M. (2023). Modulating heart rate oscillation affects plasma amyloid beta and tau levels in younger and older adults. Scientific Reports, 13(1), Article 3967. https://doi.org/10.1038/s41598-023-30167-0 Thayer, J. F. (2009). Heart rate variability: A neurovisceral integration model. In L. R. Squire (Ed.), Encyclopedia of Neuroscience (pp. 1041-1047). https://doi.org/10.1016/B978-008045046-9.01991-4 Veronese, N., Soysal, P., Demurtas, J., Solmi, M., Bruyère, O., Christodoulou, N., Ramalho, R., Fusar-Poli, P., Lappas, A. S., Pinto, D., Steen Frederiksen, K., Corbi, G. M., Karpenko, O., Georges, J., Durães, J., Schlögl, M., Yilmaz, O., Sieber, C., Shenkin, S. D., Smith, L., Reginster, J.-Y., … & World Psychiatry Association-Preventive Psychiatry Section. (2023). Physical activity and exercise for the prevention and management of mild cognitive impairment and dementia: a collaborative international guideline. European Geriatric Medicine, 14(5), 925-952. https://doi.org/10.1007/s41999-023-00858-y

INTRODUCTION:The combination of exergame-based motor-cognitive training with resonance breathing guided by heart-rate variability biofeedback (HRV-BF) targets various relevant mechanisms of action to alleviate the pathological state in mild neurocognitive disorders (mNCD). METHODS:This randomized controlled trial (RCT) investigated the effectiveness of adding this novel intervention approach to usual care in mNCD. The individualized intervention was delivered via the "Brain-IT" training concept, which was iteratively co-designed, tested, and refined with patient and public involvement. RESULTS:We observed statistically significant effects with large effect sizes for global cognitive performance, immediate verbal recall, and delayed verbal recall in favor of the intervention group. Fifty-five percent of participants showed a clinically relevant improvement in response to training. DISCUSSION:Confirmatory RCTs are warranted to investigate whether the observed improvements in cognitive performance translate to affecting the rates of progression to or onset of dementia and test the implementation of the training in clinical practice. HIGHLIGHTS:We proposed a novel intervention approach for mild neurocognitive disorders. It combines exergame-based training with biofeedback-guided resonance breathing. Our results confirm the effectiveness of this approach. Fifty-five percent of participants showed a clinically relevant improvement in response to training.

Abstract Background Early detection of cognitive impairment is among the top research priorities aimed at reducing the global burden of dementia. Currently used screening tools have high sensitivity but lack specificity at their original cut-off, while decreasing the cut-off was repeatedly shown to improve specificity, but at the cost of lower sensitivity. In 2012, a new screening tool was introduced that aims to overcome these limitations – the Quick mild cognitive impairment screen (Qmci). The original English Qmci has been rigorously validated and demonstrated high diagnostic accuracy with both good sensitivity and specificity. We aimed to determine the optimal cut-off value for the German Qmci, and evaluate its diagnostic accuracy, reliability (internal consistency) and construct validity. Methods We retrospectively analyzed data from healthy older adults (HOA; n = 43) and individuals who have a clinical diagnosis of ‘mild neurocognitive disorder’ (mNCD; n = 37) with a biomarker supported characterization of the etiology of mNCD of three studies of the ‘Brain-IT’ project. Using Youden’s Index, we calculated the optimal cut-off score to distinguish between HOA and mNCD. Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic accuracy based on the area under the curve (AUC). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Reliability (internal consistency) was analyzed by calculating Cronbach’s α. Construct validity was assessed by analyzing convergent validity between Qmci-G subdomain scores and reference assessments measuring the same neurocognitive domain. Results The optimal cut-off score for the Qmci-G was ≤ 67 (AUC = 0.96). This provided a sensitivity of 91.9% and a specificity of 90.7%. The PPV and NPV were 89.5% and 92.9%, respectively. Cronbach’s α of the Qmci-G was 0.71 (CI95% [0.65 to 0.78]). The Qmci-G demonstrated good construct validity for subtests measuring learning and memory. Subtests that measure executive functioning and/or visuo-spatial skills showed mixed findings and/or did not correlate as strongly as expected with reference assessments. Conclusion Our findings corroborate the existing evidence of the Qmci’s good diagnostic accuracy, reliability, and construct validity. Additionally, the Qmci shows potential in resolving the limitations of commonly used screening tools, such as the Montreal Cognitive Assessment. To verify these findings for the Qmci-G, testing in clinical environments and/or primary health care and direct comparisons with standard screening tools utilized in these settings are warranted.

Background Exergame-based training is currently considered a more promising training approach than conventional physical and/or cognitive training. Objectives This study aimed to provide quantitative evidence on dose-response relationships of specific exercise and training variables (training components) of exergame-based training on cognitive functioning in middle-aged to older adults (MOA). Methods We conducted a systematic review with meta-analysis including randomized controlled trials comparing the effects of exergame-based training to inactive control interventions on cognitive performance in MOA. Results The systematic literature search identified 22,928 records of which 31 studies were included. The effectiveness of exergame-based training was significantly moderated by the following training components: body position for global cognitive functioning, the type of motor-cognitive training, training location, and training administration for complex attention, and exercise intensity for executive functions. Conclusion The effectiveness of exergame-based training was moderated by several training components that have in common that they enhance the ecological validity of the training (e.g., stepping movements in a standing position). Therefore, it seems paramount that future research focuses on developing innovative novel exergame-based training concepts that incorporate these (and other) training components to enhance their ecological validity and transferability to clinical practice. We provide specific evidence-based recommendations for the application of our research findings in research and practical settings and identified and discussed several areas of interest for future research. PROSPERO registration number CRD42023418593; prospectively registered, date of registration: 1 May 2023

Abstract Background Vagally-mediated heart rate variability (vm-HRV) shows promise as a biomarker of internal training load (ITL) during exergame-based training or motor-cognitive training in general. This study evaluated the test-retest reliability of vm-HRV during exergaming in healthy older adults (HOA) and its validity to monitor ITL. Methods A within-subjects (repeated-measures) randomized study was conducted that included baseline assessments and 4 measurement sessions. Participants played 5 exergames at 3 standardized levels of external task demands (i.e., “easy”, “challenging”, and “excessive”) in random order for 90 s. Test-retest reliability was assessed on the basis of repeated-measures analyses of variance (ANOVA), intraclass correlation coefficients (ICC3,1), standard errors of measurement (SEM), and smallest detectable differences (SDD). Validity was determined by examining the effect of game level on vm-HRV in the ANOVA. Results Fourty-three HOA (67.0 ± 7.0 years; 58.1% females (25 females, 18 males); body mass index = 23.7 ± 3.0 kg·m−2) were included. Mean R-R time intervals (mRR) and parasympathetic nervous system tone index (PNS-Index) exhibited mostly good to excellent relative test-retest reliability with no systematic error. Mean SEM% and SDD% were 36.4% and 100.7% for mRR, and 44.6% and 123.7% for PNS-Index, respectively. Significant differences in mRR and PNS-Index were observed between standardized levels of external task demands, with mostly large effect sizes (mean r = 0.847). These results persisted irrespective of the type of neurocognitive domain trained and when only motoric and cognitive demands were manipulated while physical intensity was kept constant. The remaining vm-HRV parameters showed inconsistent or poor reliability and validity. Conclusion Only mRR and PNS-Index demonstrated reliable measurement and served as valid biomarkers for ITL during exergaming at a group level. Nonetheless, the presence of large SEMs hampers the detection of individual changes over time and suggests insufficient precision of these measurements at the individual level. Future research should further investigate the reliability and validity of vm-HRV with a specific focus on comparing different measurement methodologies and exercise conditions, particularly focusing on ultra-short-term HRV measurements, and investigate the potential implications (i.e., superiority to other markers of ITL or monitoring strategies?) of using vm-HRV as a biomarker of ITL.

Background Simultaneous motor-cognitive training is considered promising for preventing the decline in cognitive functioning in older adults with mild neurocognitive disorder (mNCD) and can be highly motivating when applied in the form of exergaming. The literature points to opportunities for improvement in the application of exergames in individuals with mNCD by developing novel exergames and exergame-based training concepts that are specifically tailored to patients with mNCD and ensuring the implementation of effective training components. Objective This study systematically explores the effectiveness of a newly developed exergame-based motor-cognitive training concept (called “Brain-IT”) targeted to improve cognitive functioning in older adults with mNCD. Methods A 2-arm, parallel-group, single-blinded randomized controlled trial with a 1:1 allocation ratio (ie, intervention: control), including 34 to 40 older adults with mNCD will be conducted between May 2022 and December 2023. The control group will proceed with the usual care provided by the (memory) clinics where the patients are recruited. The intervention group will perform a 12-week training intervention according to the “Brain-IT” training concept, in addition to usual care. Global cognitive functioning will be assessed as the primary outcome. As secondary outcomes, domain-specific cognitive functioning, brain structure and function, spatiotemporal parameters of gait, instrumental activities of daily living, psychosocial factors, and resting cardiac vagal modulation will be assessed. Pre- and postintervention measurements will take place within 2 weeks before starting and after completing the intervention. A 2-way analysis of covariance or the Quade nonparametric analysis of covariance will be computed for all primary and secondary outcomes, with the premeasurement value as a covariate for the predicting group factor and the postmeasurement value as the outcome variable. To determine whether the effects are substantive, partial eta-squared (η2p) effect sizes will be calculated for all primary and secondary outcomes. Results Upon the initial submission of this study protocol, 13 patients were contacted by the study team. Four patients were included in the study, 2 were excluded because they were not eligible, and 7 were being informed about the study in detail. Of the 4 included patients, 2 already completed all premeasurements and were in week 2 of the intervention period. Data collection is expected to be completed by December 2023. A manuscript of the results will be submitted for publication in a peer-reviewed open-access journal in 2024. Conclusions This study contributes to the evidence base in the highly relevant area of preventing disability because of cognitive impairment, which has been declared a public health priority by the World Health Organization. Trial Registration ClinicalTrials.gov NCT05387057; https://clinicaltrials.gov/ct2/show/NCT05387057 International Registered Report Identifier (IRRID) DERR1-10.2196/41173

Background Analyzing and adjusting training programs to increase exercise enjoyment is crucial to achieve long-term adherence and thus also maximize health benefits. The Exergame Enjoyment Questionnaire (EEQ) is the first questionnaire specifically developed to monitor exergame enjoyment. To be used in German speaking countries, the EEQ must be translated, cross-culturally adapted, and tested on its psychometric properties. Objectives The aim of this study was to develop (i.e., translate and cross-culturally adapt) the German Version of the EEQ (EEQ-G) and investigate its psychometric properties. Methods Psychometric properties of the EEQ-G were tested using a cross-sectional study design. Each participant performed two consecutive exergame sessions (i.e., ‘preferred’ and ‘unpreferred’ condition) in randomized order and rated the EEQ-G as well as reference questionnaires. Internal consistency of the EEQ-G was assessed by calculating Cronbach’s α. Construct validity was assessed by calculating Spearman’s rank correlation coefficients (rs) between the scores of the EEQ-G and reference questionnaires. Responsiveness was analyzed by performing a Wilcoxon signed-rank test between the median EEQ-G scores of the two conditions. Results Fourty-three healthy older adults (HOA; mean age = 69.4 ± 4.9 years; 53.5% females) were included. Cronbach’s α of the EEQ-G was 0.80. The rs values between the EEQ-G and reference questionnaire scores for intrinsic motivation, game enjoyment, physical activity enjoyment, and external motivation were 0.198 (p = 0.101), 0.684 (p < 0.001), 0.277 (p = 0.036), and 0.186 (p = 0.233), respectively. The EEQ-G was rated higher in the ‘preferred’ than the ‘unpreferred’ condition (p < 0.001, r = 0.756). Conclusion The EEQ-G has high internal consistency and is responsive to changes in exergame enjoyment. The highly skewed data with ceiling effects in some of the reference questionnaires deem the construct validity of the EEQ-G to be inconclusive and thus in need of further evaluation.

BackgroundExergames provide a promising new approach to implement simultaneous motor–cognitive training, which may support preventing the decline in cognitive functioning in older adults who have a mild neurocognitive disorder (mNCD).ObjectivesTo evaluate feasibility, system usability, and acceptance of “Brain-IT”, a newly developed training concept combining exergame-based motor-cognitive training and heart rate variability (HRV) guided resonance breathing for the secondary prevention of mNCD.MethodsA pilot randomized controlled trial (RCT) with an allocation ratio of 2:1 (i.e., intervention:control) was conducted. The control group proceeded with usual care. The intervention group performed a 12-week training according to the “Brain-IT” training concept implemented with the “Senso Flex” (Dividat AG) exergaming system in addition to usual care. Feasibility and usability outcomes were analyzed using descriptive statistics. User acceptance was analyzed qualitatively and using Friedman analysis of variance (ANOVA), as well as Wilcoxon signed-rank tests.ResultsEighteen participants (77.3 ± 9.8 years; 44.4% females) were included. On average, we recruited 2.2 participants per month, and 35.3% of the individuals contacted were included. The intervention group had an attrition rate of 20% and mean adherence and compliance rates of 85.0 and 84.1%, respectively. The mean system usability score, measured with the system usability scale, was 71.7. High levels of exergame enjoyment, an increase in exergame enjoyment, and internalization of training motivation with large effect sizes (p = 0.03, r = 0.75 and p = 0.03, r = 0.74, respectively), as well as acceptable perceived usefulness, were observed. Preliminary data on the effects of the “Brain-IT” training are promising.ConclusionThe feasibility and usability of the “Brain-IT” training are acceptable. However, frequent occurrences of technical problems and difficulties in using the exergame training system were identified as barriers to performing the “Brain-IT” training. To optimize feasibility, either improvements or alternative solutions are required in the hardware and software of the exergame used to implement the “Brain-IT” training. The “Brain-IT” training itself was well-accepted by older adults who have mNCD. Therefore, the effectiveness of the “Brain-IT” training concept should be investigated in future studies.Trial registrationclinicaltrials.gov/ct2/show/NCT04996654.

Background Exergames have attracted growing interest in the prevention and treatment of neurocognitive disorders. The most effective exergame and training components (ie, exercise and training variables such as frequency, intensity, duration, or volume of training and type and content of specific exergame scenarios) however remain to be established for older adults with mild neurocognitive disorders (mNCDs). Regarding the design and development of novel exergame-based training concepts, it seems of crucial importance to explicitly include the intended users’ perspective by adopting an interactive and participatory design that includes end users throughout different iterative cycles of development. Objective This study aimed to determine the capabilities, treatment preferences, and motivators for the training of older adults with mNCD and the perspectives of individuals on training goals and settings and requirements for exergame and training components. Methods A qualitative study including expert focus groups and individual semistructured in-depth patient interviews was conducted. Data were transcribed to a written format to perform qualitative content analysis using QCAmap software. Results In total, 10 experts and health care professionals (80% females) and 8 older adults with mNCD (38% females; mean age 82.4, SD 6.2 years) were recruited until data saturation was observed. Conclusions The psychosocial consequences of patients’ self-perceived cognitive deterioration might be more burdensome than the cognitive changes themselves. Older adults with mNCD prefer integrative forms of training (such as exergaming) and are primarily motivated by enjoyment or fun in exercising and the effectiveness of the training. Putting the synthesized perspectives of training goals, settings, and requirements for exergames and training components into context, our considerations point to opportunities for improvement in research and rehabilitation, either by adapting existing exergames to patients with mNCDs or by developing novel exergames and exergame-based training concepts specifically tailored to meet patient requirements and needs.