Diagnostic accuracy, reliability, and construct validity of the German quick mild cognitive impairment screen.

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.

Test-retest reliability and validity of vagally-mediated heart rate variability to monitor internal training load in older adults: a within-subjects (repeated-measures) randomized study.

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.

PEMOCS: theory derivation of a concept for PErsonalized MOtor-Cognitive exergame training in chronic Stroke-a methodological paper with an application example.

Background: Coping 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. Methods: The 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. Results: A 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. Conclusion: We 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.

Components of effective exergame-based training to improve cognitive functioning in middle-aged to older adults - A systematic review and meta-analysis.

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.

"Brain-IT": Exergame training with biofeedback breathing in neurocognitive disorders.

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.

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.

Background: Exergames 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). Objectives: To 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. Methods: A 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. Results: Eighteen 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. Conclusion: The 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 registration: clinicaltrials.gov/ct2/show/NCT04996654.

Development and initial validation of the German version of the Exergame Enjoyment Questionnaire (EEQ-G).

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.

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.

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.

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.

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.

Estimating flexibility preferences to resolve temporal scheduling conflicts in activity-based modelling.

This paper presents a novel activity-based demand model that combines an optimisation framework for continuous temporal scheduling decisions (i.e. activity timings and durations) with traditional discrete choice models for non-temporal choice dimensions (i.e. activity participation, number and type of tours, and destinations). The central idea of our approach is that individuals resolve temporal scheduling conflicts that arise from overlapping activities, e.g. needing to work and desiring to shop at the same time, in order to maximise their daily utility. Flexibility parameters capture behavioural preferences that penalise deviations from desired timings. This framework has three advantages over existing activity-based modelling approaches: (i) the time conflicts between different temporal scheduling decisions including the activity sequence are treated jointly; (ii) flexibility parameters follow a utility maximisation approach; and (iii) the framework can be used to estimate and simulate a city-scale case study in reasonable time. We introduce an estimation routine that allows flexibility parameters to be estimated using real-world observations as well as a simulation routine to efficiently resolve temporal conflicts using an optimisation model. The framework is applied to the full-time workers of a synthetic population for the city of Lausanne, Switzerland. We validate the model results against reported schedules. The results demonstrate the capabilities of our approach to reproduce empirical observations in a real-world case study.

Making the Best Out of IT: Design and Development of Exergames for Older Adults With Mild Neurocognitive Disorder - A Methodological Paper.

Background: Utilizing information technology (IT) systems, for example in form of computerized cognitive screening or exergame-based (also called active videogames) training, has gained growing interest for supporting healthy aging and to detect, prevent and treat neurocognitive disorders (NCD). To ameliorate the effectiveness of exergaming, the neurobiological mechanisms as well as the most effective components for exergame-based training remain to be established. At the same time, it is important to account for the end-users' capabilities, preferences, and therapeutic needs during the design and development process to foster the usability and acceptance of the resulting program in clinical practice. This will positively influence adherence to the resulting exergame-based training program, which, in turn, favors more distinct training-related neurobiological effects. Objectives and Methods: This methodological paper describes the design and development process of novel exergame-based training concepts guided by a recently proposed methodological framework: The 'Multidisciplinary Iterative Design of Exergames (MIDE): A Framework for Supporting the Design, Development, and Evaluation of Exergames for Health' (Li et al., 2020). Case Study: A step-by-step application of the MIDE-framework as a specific guidance in an ongoing project aiming to design, develop, and evaluate an exergame-based training concept with the aim to halt and/or reduce cognitive decline and improve quality of life in older adults with mild neurocognitive disorder (mNCD) is illustrated. Discussion and Conclusion: The development of novel exergame-based training concepts is greatly facilitated when it is based on a theoretical framework (e.g., the MIDE-framework). Applying this 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 is expected to foster the usability and acceptance of the resulting exergame intervention in "real life" settings. Therefore, it is strongly recommended to implement a theoretical framework (e.g., the MIDE-framework) for future research projects in line with well-known checklists to improve completeness of reporting and replicability when serious games for motor-cognitive rehabilitation purposes are to be developed.

Can Reactivity of Heart Rate Variability Be a Potential Biomarker and Monitoring Tool to Promote Healthy Aging? A Systematic Review With Meta-Analyses.

Background: Monitoring phasic responses of heart rate variability (HRV) in terms of HRV reactivity [i. e., the absolute change from resting state to on-task (i.e., absolute values of HRV measured during exercise)] might provide useful insights into the individual psychophysiological responses of healthy middle-aged to older adults (HOA) to cognitive and physical exercises. Objectives: To summarize the evidence of phasic HRV responses to cognitive and physical exercises, and to evaluate key moderating factors influencing these responses. Methods: A systematic review with meta-analyses was performed. Publications up to May 2020 of the databases Medline (EBSCO), Embase, Cochrane Library, CINAHL, Psycinfo, Web of Science, Scopus, and Pedro were considered. Controlled clinical trials and observational studies measuring phasic HRV responses to cognitive and/or physical exercises in HOA (≥50 years) were included. Results: The initial search identified 6,828 articles, of which 43 were included into the systematic review. Compared to resting state, vagally-mediated HRV indices were significantly reduced during all types of exercises [Hedge's g = -0.608, 95 % CI (-0.999 to -0.218), p = 0.002] indicating a significant parasympathetic withdrawal compared to rest. The key moderating variables of these responses identified included exercise intensity for physical exercises, and participant characteristics (i.e., level of cognitive functioning, physical fitness), task demands (i.e., task complexity and modality) and the individual responses to these cognitive challenges for cognitive exercises. In particular, higher task demands (task complexity and physical exercise intensity) were related to larger HRV reactivities. Better physical fitness and cognition were associated with lower HRV reactivities. Additionally, HRV reactivity appeared to be sensitive to training-induced cognitive and neural changes. Conclusion: HRV reactivity seems to be a promising biomarker for monitoring internal training load and evaluating neurobiological effects of training interventions. Further research is warranted to evaluate the potential of HRV reactivity as a monitoring parameter to guide cognitive-motor training interventions and/or as a biomarker for cognitive impairment. This may facilitate the early detection of cognitive impairment as well as allow individualized training adaptations that, in turn, support the healthy aging process by optimizing individual exercise dose and progression of cognitive-motor training.