Brain Health Indicators Following Acute Neuro-Exergaming: Biomarker and Cognition in Mild Cognitive Impairment (MCI) after Pedal-n-Play (iPACES).

Facing an unrelenting rise in dementia cases worldwide, researchers are exploring non-pharmacological ways to ameliorate cognitive decline in later life. Twenty older adults completed assessments before and after a single bout of interactive physical and cognitive exercise, by playing a neuro-exergame that required pedaling and steering to control progress in a tablet-based video game tailored to impact executive function (the interactive Physical and Cognitive Exercise System; iPACES v2). This study explored the cognitive and biomarker outcomes for participants with mild cognitive impairment (MCI) and normative older adults after 20 min of pedal-to-play exercise. Neuropsychological and salivary assessments were performed pre- and post-exercise to assess the impact. Repeated-measures ANOVAs revealed significant interaction effects, with MCI participants experiencing greater changes in executive function and alpha-amylase levels than normative older adults; within-group changes were also significant. This study provides further data regarding cognitive effects and potential mechanisms of action for exercise as an intervention for MCI.

Screening for Alzheimer's Disease Using Saliva: A New Approach Based on Machine Learning and Raman Hyperspectroscopy.

BACKGROUND: Alzheimer's disease and related dementias (ADRDs) are being diagnosed at epidemic rates, with incidence to triple from 35 to 115 million cases worldwide. Most ADRDs are characterized by progressive neurodegeneration, and Alzheimer's disease (AD) is the sixth leading cause of death in the United States. The ideal moment for diagnosing ADRDs is during the earliest stages of its progression; however, current diagnostic methods are inefficient, expensive, and unsuccessful at making diagnoses during the earliest stages of the disease. OBJECTIVE: The aim of this project was to utilize Raman hyperspectroscopy in combination with machine learning to develop a novel method for the diagnosis of AD based on the analysis of saliva. METHODS: Raman hyperspectroscopy was used to analyze saliva samples collected from normative, AD, and mild cognitive impairment (MCI) individuals. Genetic Algorithm and Artificial Neural Networks machine learning techniques were applied to the spectral dataset to build a diagnostic algorithm. RESULTS: Internal cross-validation showed 99% accuracy for differentiating the three classes; blind external validation was conducted using an independent dataset to further verify the results, achieving 100% accuracy. CONCLUSION: Raman hyperspectroscopic analysis of saliva has a remarkable potential for use as a non-invasive, efficient, and accurate method for diagnosing AD.

The interactive Physical and Cognitive Exercise System (iPACES™): effects of a 3-month in-home pilot clinical trial for mild cognitive impairment and caregivers.

BACKGROUND: Alzheimer's and related dementias are on the rise, and older adults and their families are seeking accessible and effective ways to stave off or ameliorate mild cognitive impairment (MCI). AIM: This pilot clinical trial (ClinicalTrials.gov Identifier: 03069391) examined neuropsychological and neurobiological outcomes of interactive physical and mental exercise. PARTICIPANTS AND METHODS: Older adults (MCI and caregivers) were enrolled in a 3-month, in-home trial of a portable neuro-exergame (the interactive Physical and Cognitive Exercise System [iPACES™]), in which they pedaled and steered along a virtual bike path to complete a list of errands (Memory Lane™). Neuropsychological function and salivary biomarkers were measured at pre-, mid-, and posttrial. Ten older adults complied with the recommended use of iPACES (complete dose; ≥2×/wk, 67% of the 15 who also had pre- and postevaluation data). Statistical analyses compared change over time and also change among those with a complete dose vs inadequate dose. Correlations between change in neuropsychological and biomarker measures were also examined. RESULTS: Executive function and verbal memory increased after 3 months (p = 0.01; no significant change was found with an inadequate dose). Change in salivary biomarkers was moderately associated with increasing cognition (cortisol, r = 0.68; IGF-1, r = 0.37). CONCLUSION: Further research is needed, but these pilot data provide preliminary indications to suggest neuro-exergaming can impact cognitive function, perhaps via neurobiological mechanisms, and as such may provide an effective and practical way to promote healthy aging.

The Enhanced Interactive Physical and Cognitive Exercise System (iPACESTM v2.0): Pilot Clinical Trial of an In-Home iPad-Based Neuro-Exergame for Mild Cognitive Impairment (MCI).

Given increasing longevity worldwide, older adults and caregivers are seeking ways to curb cognitive decline especially for those with mild cognitive impairment (MCI, now mild neurocognitive disorder, mNCD, Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-V). This quasi-experimental, within-subjects pilot clinical trial was designed to replicate and extend the study of cognitive benefits for MCI by improving upon our prior interactive Physical and Cognitive Exercise Study (iPACESTM v1.0) by increasing the usability of the neuro-exergame and exploring possible underlying neurobiological mechanisms. Older adults were enrolled in a three-month, in-home trial of a portable neuro-exergame (iPACES™ v2.0) where participants pedaled and steered along a virtual bike path (Memory Lane™). Neuropsychological function was assessed at baseline after component familiarization intervals (e.g., two weeks of exercise-only, game-only, etc.) and after three months of interactive neuro-exergame intervention. Fourteen participants were enrolled in the study and seven completed the final evaluation. Intent-to-treat analyses were conducted with imputed missing data (total n = 14). Significant improvement in executive function (Stroop) was found (d = 0.68, p = 0.02) only. Changes in salivary biomarkers (cortisol and insulin-like growth factor 1; IGF-1) were significantly associated with improved cognition. Further research is needed, but pilot data suggest that a portable in-home neuro-exergame may be an additional, practical tool to fight back against cognitive decline and dementia.

The Aerobic and Cognitive Exercise Study (ACES) for Community-Dwelling Older Adults With or At-Risk for Mild Cognitive Impairment (MCI): Neuropsychological, Neurobiological and Neuroimaging Outcomes of a Randomized Clinical Trial.

Prior research has found that cognitive benefits of physical exercise and brain health in older adults may be enhanced when mental exercise is interactive simultaneously, as in exergaming. It is unclear whether the cognitive benefit can be maximized by increasing the degree of mental challenge during exercise. This randomized clinical trial (RCT), the Aerobic and Cognitive Exercise Study (ACES) sought to replicate and extend prior findings of added cognitive benefit from exergaming to those with or at risk for mild cognitive impairment (MCI). ACES compares the effects of 6 months of an exer-tour (virtual reality bike rides) with the effects of a more effortful exer-score (pedaling through a videogame to score points). Fourteen community-dwelling older adults meeting screening criteria for MCI (sMCI) were adherent to their assigned exercise for 6 months. The primary outcome was executive function, while secondary outcomes included memory and everyday cognitive function. Exer-tour and exer-score yielded significant moderate effects on executive function (Stroop A/C; d's = 0.51 and 0.47); there was no significant interaction effect. However, after 3 months the exer-tour revealed a significant and moderate effect, while exer-score showed little impact, as did a game-only condition. Both exer-tour and exer-score conditions also resulted in significant improvements in verbal memory. Effects appear to generalize to self-reported everyday cognitive function. Pilot data, including salivary biomarkers and structural MRI, were gathered at baseline and 6 months; exercise dose was associated with increased BDNF as well as increased gray matter volume in the PFC and ACC. Improvement in memory was associated with an increase in the DLPFC. Improved executive function was associated with increased expression of exosomal miRNA-9. Interactive physical and cognitive exercise (both high and low mental challenge) yielded similarly significant cognitive benefit for adherent sMCI exercisers over 6 months. A larger RCT is needed to confirm these findings. Further innovation and clinical trial data are needed to develop accessible, yet engaging and effective interventions to combat cognitive decline for the growing MCI population. ClinicalTrials.gov ID: NCT02237560.

Neuropsychological Benefits of Neuro-Exergaming for Older Adults: A Pilot Study of an Interactive Physical and Cognitive Exercise System (iPACES).

Dementia cases are on the rise and researchers seek innovative ways to prevent or ameliorate cognitive impairment in later life. Some research has reported that combining mental and physical exercise may benefit cognition more than either alone. This randomized pilot trial examined the feasibility and cognitive benefit for older adults (n = 30) of a single bout of neuro-exergaming (physical activity with cognitive training) using an interactive physical and cognitive exercise system (iPACES), compared with that of exergaming or neurogaming alone. Intent-to-treat and sensitivity analyses were conducted using repeated-measures ANOVA, controlling for age, sex, and education. A significant interaction effect was found for executive function (Color Trails 2), with a significant improvement in the neuro-exergaming condition. Results demonstrate feasibility for older adults to use a novel and theoretically-derived neuro-exergame, and also provide promising new evidence that neuro-exergaming can yield greater cognitive benefit than either of its component parts.

Comparing the effects of an acute bout of physical exercise with an acute bout of interactive mental and physical exercise on electrophysiology and executive functioning in younger and older adults.

BACKGROUND: Physical exercise has been shown to improve cognitive and neural functioning in older adults. AIMS AND METHODS: The current study compared the effects of an acute bout of physical exercise with a bout of interactive mental and physical exercise (i.e., "exergaming") on executive (Stroop) task performance and event-related potential (ERP) amplitudes in younger and older adults. RESULTS: Results revealed enhanced executive task performance in younger and older adults after exercise, with no differences in performance between exercise conditions. Stroop (RT) performance in older adults improved more than in younger adults from pre- to post-exercise. A significant increase in EEG amplitude from pre- to post-exercise was found at the Cz site from 320 to 700 ms post-stimulus for both younger and older adults, with older adults demonstrating a larger Stroop interference effect. While younger adults exhibited overall greater EEG amplitudes than older adults, they showed no differences between congruent and incongruent trials (i.e., minimal interference). Compared to peers with higher BMI (body mass index), older adults with lower BMI showed a greater reduction in Stroop interference effects from pre- to post-exercise. DISCUSSION AND CONCLUSIONS: The beneficial effects of an acute bout of physical exercise on cognitive and neural functioning in younger and older adults were confirmed, with no difference between standard exercise and exergaming. Findings suggest that BMI, sometimes used as a proxy for fitness level, may modulate benefits that older adults derive from an acute bout of exercise. Findings have implications for future research that seeks to investigate unique effects of exergaming when compared to standard physical exercise.

Aerobic and Cognitive Exercise (ACE) Pilot Study for Older Adults: Executive Function Improves with Cognitive Challenge While Exergaming.

Dementia cases are increasing worldwide; thus, investigators seek to identify interventions that might prevent or ameliorate cognitive decline in later life. Extensive research confirms the benefits of physical exercise for brain health, yet only a fraction of older adults exercise regularly. Interactive mental and physical exercise, as in aerobic exergaming, not only motivates, but has also been found to yield cognitive benefit above and beyond traditional exercise. This pilot study sought to investigate whether greater cognitive challenge while exergaming would yield differential outcomes in executive function and generalize to everyday functioning. Sixty-four community based older adults (mean age=82) were randomly assigned to pedal a stationary bike, while interactively engaging on-screen with: (1) a low cognitive demand task (bike tour), or (2) a high cognitive demand task (video game). Executive function (indices from Trails, Stroop and Digit Span) was assessed before and after a single-bout and 3-month exercise intervention. Significant group × time interactions were found after a single-bout (Color Trails) and after 3 months of exergaming (Stroop; among 20 adherents). Those in the high cognitive demand group performed better than those in the low cognitive dose condition. Everyday function improved across both exercise conditions. Pilot data indicate that for older adults, cognitive benefit while exergaming increased concomitantly with higher doses of interactive mental challenge.

Executive function and self-regulated exergaming adherence among older adults.

The rise in dementia and the evidence of cognitive benefits of exercise for the older adult population together make salient the research into variables affecting cognitive benefit and exercise behavior. One promising avenue for increasing exercise participation has been the introduction of exergaming, a type of exercise that works in combination with virtual reality to enhance both the exercise experience and health outcomes. Past research has revealed that executive function (EF) was related to greater use of self-regulatory strategies, which in turn was related to greater adherence to exercise following an intervention (McAuley et al., 2011). Best et al. (2014) found improvement in EF related to adherence to exercise post- intervention. Anderson-Hanley et al. (2012) found that for older adults aerobic exergaming yielded greater cognitive benefit than traditional exercise alone; however, questions remain as to the possible impact of greater cognitive benefit and other factors on participants' involvement in exercise following the end of an intervention. The current study presents follow-up data exploring the relationship between EF, self-regulation, and exercise behavior in the post-intervention (naturalistic) period. Herein, it was predicted that higher EF at the start of the naturalistic window, would predict subsequent exercise with an exergame. Contrary to expectations, results suggest that those with poorer EF are likely to exergame more frequently. The results of this study contradict previous literature, but suggest an interesting relationship between EF, self-regulation, and exercise behaviors when exergaming is employed, particularly with older adults with some cognitive decline. We hypothesize that other factors may be at work, perhaps expectation of cognitive benefit might act as a unique motivator.

The fuld object-memory evaluation: development and validation of an alternate form.

The Fuld Object-Memory Evaluation (FOME) uses multisensory (tactile, visual, and verbal) encoding of objects for assessing memory, with particular clinical and research application in older adults. This preliminary study reports the first known psychometric data on the development of an alternate form of the FOME. Data were drawn from 102 independent-living older adults participating in a larger clinical trial. Seventy participants completed three versions of the shortened administration of the FOME, and comparability of forms was established by significant, moderate intraclass correlation coefficients for immediate and delayed recall scores. Reliable change indexes indicate the new alternate form performs well, with minimal practice or learning effects. Evidence of convergent and discriminant validity was documented using the Rey Auditory Verbal Learning Test, category fluency task, and North American Adult Reading Test. Normative data are provided stratified by age for participants completing at least one of three time points (n = 96). Results of this preliminary study provide evidence for the comparability and construct validity of a new alternate form of the FOME with prior forms. An additional well-validated form of the FOME has practical implications for serial testing often required in clinical practice and research design.

Neuropsychological benefits of stationary bike exercise and a cybercycle exergame for older adults with diabetes: an exploratory analysis.

OBJECTIVE: This quasi-experimental exploratory study investigated neuropsychological effects of exercise among older adults with diabetes mellitus (DM) compared with adults without diabetes (non-DM), and it examined the feasibility of using a stationary bike exergame as a form of exercise for older adults with and without diabetes. It is a secondary analysis that uses a small dataset from a larger randomized clinical trial (RCT) called the Cybercycle Study, which compared cognitive and physiological effects of traditional stationary cycling versus cybercycling. METHODS: In the RCT and the secondary analysis, older adults living in eight independent living retirement facilities in the state of New York were enrolled in the study and assigned to exercise five times per week for 45 min per session (two times per week was considered acceptable for retention in the study) by using a stationary bicycle over the course of 3 months. They were randomly assigned to use either a standard stationary bicycle or a "cybercycle" with a video screen that displayed virtual terrains, virtual tours, and racing games with virtual competitors. For this secondary analysis, participants in the RCT who had type 2 DM (n = 10) were compared with age-matched non-DM exercisers (n = 10). The relationship between exercise and executive function (i.e., Color Trials 2, Digit Span Backwards, and Stroop C tests) was examined for DM and non-DM patients. RESULTS: Older adults with and without diabetes were able to use cybercycles successfully and complete the study, so the feasibility of this form of exercise for this population was supported. However, in contrast with the larger RCT, this small subset did not demonstrate statistically significant differences in executive function between the participants who used cybercycles and those who used stationary bikes with no games or virtual content on a video screen. Therefore, the study combined the two groups and called them "exercisers" and compared cognitive outcomes for DM versus non-DM patients. As predicted, exercisers with DM exhibited significant gains in executive function as measured by the Color Trails 2 test, controlling for age and education, while non-DM exercisers did not significantly gain in this measure [group × time interaction, F(1,16]) = 9.75; p = .007]. CONCLUSIONS: These preliminary results support the growing literature that finds that exercise may improve cognition among older adult with DM. Additional research is needed to clarify why certain aspects of executive function might be differentially affected. The current findings may encourage physicians to prescribe exercise for diabetes management and may help motivate DM patients' compliance for engaging in physical activity.

Virtual and live social facilitation while exergaming: competitiveness moderates exercise intensity.

Grounded in social facilitation theory, this study compared the impact on exercise intensity of a virtual versus a live competitor, when riding a virtual reality-enhanced stationary bike ("cybercycle"). It was hypothesized that competitiveness would moderate effects. Twenty-three female college students were exposed to three conditions on a cybercycle: solo training, virtual competitor, and live competitor. After training without a competitor (solo condition for familiarization with equipment), participants competed against a virtual avatar or live rider (random order of presentation). A repeated-measures analysis revealed a significant condition (virtual/live) by competitiveness (high/low) interaction for exercise intensity (watts). More competitive participants exhibited significantly greater exercise intensity when competing against a live versus virtual competitor. The implication is that live competitors can have an added social facilitation effect and influence exercise intensity, although competitiveness moderates this effect.

Exergaming and older adult cognition: a cluster randomized clinical trial.

BACKGROUND: Dementia cases may reach 100 million by 2050. Interventions are sought to curb or prevent cognitive decline. Exercise yields cognitive benefits, but few older adults exercise. Virtual reality-enhanced exercise or "exergames" may elicit greater participation. PURPOSE: To test the following hypotheses: (1) stationary cycling with virtual reality tours ("cybercycle") will enhance executive function and clinical status more than traditional exercise; (2) exercise effort will explain improvement; and (3) brain-derived neurotrophic growth factor (BDNF) will increase. DESIGN: Multi-site cluster randomized clinical trial (RCT) of the impact of 3 months of cybercycling versus traditional exercise, on cognitive function in older adults. Data were collected in 2008-2010; analyses were conducted in 2010-2011. SETTING/PARTICIPANTS: 102 older adults from eight retirement communities enrolled; 79 were randomized and 63 completed. INTERVENTIONS: A recumbent stationary ergometer was utilized; virtual reality tours and competitors were enabled on the cybercycle. MAIN OUTCOME MEASURES: Executive function (Color Trails Difference, Stroop C, Digits Backward); clinical status (mild cognitive impairment; MCI); exercise effort/fitness; and plasma BDNF. RESULTS: Intent-to-treat analyses, controlling for age, education, and cluster randomization, revealed a significant group X time interaction for composite executive function (p=0.002). Cybercycling yielded a medium effect over traditional exercise (d=0.50). Cybercyclists had a 23% relative risk reduction in clinical progression to MCI. Exercise effort and fitness were comparable, suggesting another underlying mechanism. A significant group X time interaction for BDNF (p=0.05) indicated enhanced neuroplasticity among cybercyclists. CONCLUSIONS: Cybercycling older adults achieved better cognitive function than traditional exercisers, for the same effort, suggesting that simultaneous cognitive and physical exercise has greater potential for preventing cognitive decline. TRIAL REGISTRATION: This study is registered at Clinicaltrials.gov NCT01167400.

Neuropsychological and neurophysiological effects of strengthening exercise for early dementia: a pilot study.

Research demonstrates a positive effect of aerobic exercise on cognitive functioning in older adults. Unfortunately, aerobic exercise is often contraindicated for older adults due to cardiovascular and functional limitations. Low-intensity strengthening exercise may offer a practical alternative, but the neuropsychological benefits and potential neurophysiological mechanisms are less well understood. The current study evaluated the effects of a 10-week strengthening exercise intervention on cognitive functioning and EEG in a sample of 13 older adults with early dementia, and 9 normative controls. Results revealed beneficial effects of strengthening exercise on verbal memory coupled with frontal beta and delta power asymmetries and N200 amplitude asymmetry. Results point to increased cognitive efficiency following 10 weeks of strengthening exercise. The findings suggest it is feasible to conduct a strengthening intervention with early dementia patients, and to gather neuropsychological and neurophysiological data to evaluate outcomes. Strengthening exercise may serve as a useful alternative to aerobic exercise.

Social facilitation in virtual reality-enhanced exercise: competitiveness moderates exercise effort of older adults.

This study examined the effect of virtual social facilitation and competitiveness on exercise effort in exergaming older adults. Fourteen exergaming older adults participated. Competitiveness was assessed prior to the start of exercise. Participants were trained to ride a "cybercycle;" a virtual reality-enhanced stationary bike with interactive competition. After establishing a cybercycling baseline, competitive avatars were introduced. Pedaling effort (watts) was assessed. Repeated measures ANOVA revealed a significant group (high vs low competitiveness) × time (pre- to post-avatar) interaction (F[1,12] = 13.1, P = 0.003). Virtual social facilitation increased exercise effort among more competitive exercisers. Exercise programs that match competitiveness may maximize exercise effort.

Autism and exergaming: effects on repetitive behaviors and cognition.

Autism is a neurodevelopmental disorder that leads to impairment in social skills and delay in language development, and results in repetitive behaviors and restricted interests that impede academic and social involvement. Physical exercise has been shown to decrease repetitive behaviors in autistic children and improve cognitive function across the life-span. Exergaming combines physical and mental exercise simultaneously by linking physical activity movements to video game control and may yield better compliance with exercise. In this investigation, two pilot studies explored the potential behavioral and cognitive benefits of exergaming. In Pilot I, twelve children with autism spectrum disorders completed a control task and an acute bout of Dance Dance Revolution (DDR); in Pilot II, ten additional youths completed an acute bout of cyber cycling. Repetitive behaviors and executive function were measured before and after each activity. Repetitive behaviors significantly decreased, while performance on Digits Backwards improved following the exergaming conditions compared with the control condition. Additional research is needed to replicate these findings, and to explore the application of exergaming for the management of behavioral disturbance and to increase cognitive control in children on the autism spectrum.

Cognitive health benefits of strengthening exercise for community-dwelling older adults.

While aerobic exercise has been linked to improved performance on cognitive tasks of executive functioning among older adults, not all older adults can avail themselves of such exercise due to physical limitations. In this study, community-dwelling older adults were evaluated on tasks of executive functioning before and after a month-long strengthening, nonaerobic exercise program. A total of 16 participants who engaged in such exercise showed significantly improved scores on Digits Backward and Stroop C tasks when compared to 16 participants who were on an exercise waiting list. Positive benefits of strengthening exercise on cognition are supported. Additional research is needed to clarify the generalizability of these findings.

Measurement of coping and stress responses in women with breast cancer.

The development of the Responses to Stress Questionnaire-cancer version (RSQ-CV) to assess coping with and responses to the stress of breast cancer is described. The RSQ-CV was completed by 232 women with breast cancer near the time of their diagnosis. Confirmatory factor analyses verified a model that includes three voluntary coping factors (primary control engagement coping, secondary control engagement coping, disengagement coping) and two involuntary stress response factors (involuntary engagement, involuntary disengagement). Internal consistency reliability, and stability over 12 weeks for the five factors were adequate to excellent. Convergent and discriminant validity was examined through correlations with measures of intrusive thoughts, avoidance, and dimensions of perceived control. Significant correlations with symptoms of anxiety and depression are also reported. Applications of the RSQ-CV for research with breast cancer patients are discussed.

The effects of journaling for women with newly diagnosed breast cancer.

Forty-three women newly diagnosed with breast cancer participated in this study, which examined the role of expressive journal writing characteristics on mood over the course of a 12-week support group. Writing was analyzed using the linguistic inquiry and word count program. Writing characteristics that were examined included: average word count, number of journal entries, positive and negative emotion words, the ratio of positive to negative words, and the use of cognitive mechanism words (i.e. insight and causal words). Regression analyses revealed that increased levels of anxiety and depression, post-intervention, were predicted by the prevalence of negative emotion in writing. Unique variance in mood (anxiety and depression) was accounted for by expression of negative emotion (7 and 6%, respectively). These relationships were significant (p<0.05) and remained significant even after accounting for pre-intervention levels of distress, and for the quantity and frequency of writing. These findings suggest the need for additional research into the naturalistic application of journaling so that appropriate recommendations for writing (e.g. focus, timing, amount) can be offered to patients who might choose to utilize this approach for coping with the stresses of cancer diagnosis and treatment.