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. 2024 Mar 15;64(6):gnae028. doi: 10.1093/geront/gnae028

The Effects of Exergame Telerehabilitation in Persons With Subjective Cognitive Decline

Dereck L Salisbury 1,✉, Keenan A Pituch 2, Fang Yu 3
Editor: Joseph E Gaugler
PMCID: PMC11138364  PMID: 38486359

Abstract

Background and Objectives

The primary aim of this Stage IB randomized controlled trial (RCT) was to test the preliminary effects of a dual-task exergaming telerehabilitation intervention on cognition and aerobic fitness, compared to aerobic exercise (AEx) only and attention control (stretching) in older adults with subjective cognitive decline.

Research Design and Methods

This RCT randomized 39 participants on a 2:1:1 allocation ratio to supervised exergame (n = 20), AEx (n = 11), and stretching (n = 8) for 12 weeks. The dual-task exergaming was concurrent moderate-intensity cycling and BrainFitRx cognitive telerehabilitation. Cognition was assessed by NIH Toolbox Cognitive Battery and aerobic fitness by 6-minute walk test (6MWT) and shuttle walk test.

Results

The participants were 74.6 (7.4) years old and 69% were female. The effect of time was significant, F(1, 23.9) = 13.16, p = .001, for the Fluid Composite score, and significant within-group changes were seen for the exergame group, t(14.08) = 2.53, p = .024, d = 0.33. Between-group changes did not reach significant levels for any cognitive test. Between-group changes for the 6MWT were not significant.

Discussion and Implications

The exergame participants further improved their fluid cognition, whereas the AEx and stretching groups did not, indicating a potential synergistic effect from AEx and cognitive training. The aerobic fitness changes were similar between the exergame and AEx-only groups, indicating that the feasibility of adding cognitive training to AEx concurrently without sacrificing gains in aerobic fitness from AEx. This study shows the flexibility of exergame delivery and its potentially therapeutic effects in persons at risk for Alzheimer’s dementia.

Clinical Trial Registration Number

NCT04311736

Keywords: Alzheimer’s disease, Cardiorespiratory fitness, Cognitive function, Physical activity/exercise

Subjective cognitive decline (SCD) is typically regarded as the preclinical phase of Alzheimer’s disease (AD; Taylor et al., 2018). Currently, population-based studies suggest that between 50% and 80% of older individuals (aged 70 years and older) who perform within normal ranges on cognitive tests report SCD when asked (Jessen et al., 2010; van Harten et al., 2018). This preclinical state offers a therapeutic window where interventions have strong potential to prevent or delay AD’s progression to the clinical phase (van Harten et al., 2018), which is important as interventions at clinical phases of AD provide only modest benefits (Cummings et al., 2014). Two potential interventions are aerobic exercise (AEx) and cognitive training. It is believed that AEx can have positive effects on cognition, brain integrity, and AD risk mainly through enhancing cerebral blood flow, neurogenesis, and aerobic fitness while reducing potentially modifiable AD risk factors (Burns et al., 2008; Huuha et al., 2022; Tari, Norevik et al., 2019). Cognitive training is thought to generally target cognitive structures and facilitate functional connectivity within areas of the brain (Martin et al., 2011). When used together (e.g., dual-task therapy), they potentially can provide a synergistic effect on brain structure and function, as each works through distinct mechanisms. One form of dual-task therapy is exergaming (“interactive digital or video games that require participants to be physically active to play”; Anderson-Hanley et al., 2012). This dual-task therapy is thought to provide a therapeutic effect via attenuation of AD neurodegeneration and enhancement of neuroplasticity (Torre & Temprado, 2021). The evidence for dual-task exergaming has been growing (Torre & Temprado, 2022), but several questions still remain.

First, the majority of concurrent AEx and cognitive training (and in particular exergaming) have mainly focused on cognitive benefits in clinical phases of AD (i.e., mild cognitive impairment, dementia; Swinnen et al., 2022; Zhao et al., 2020) instead of AD dementia prevention (i.e., preclinical phase), so it is currently unclear how effective exergaming is in persons with SCD. Additionally, the majority of dual-task AEx and cognitive training studies have employed a sequential style of delivery (i.e., AEx followed by cognitive training; Torre & Temprado, 2021), where the AEx delivery is not affected by outside factors (i.e., distraction from other training stimuli). Currently, it is unclear whether aerobic fitness gains are affected when a simultaneous delivery (rather than a traditional sequential mode) is implemented, as a possibility exists that the cognitive training inherent to exergaming may become too distracting (and impact effort of AEx) and therefore prevent gains in aerobic fitness. This is important in the context of the cardiorespiratory fitness hypothesis, which suggests that cardiorespiratory (i.e., aerobic) fitness is the physiological mediator that explains the relationship between physical exercise and improved cognitive performance (Burns et al., 2008).

The primary aim of this Stage 1B RCT (National Institutes on Aging [NIA], 2023) was to test the preliminary effects of a dual-task exergame intervention (BrainFitRx [simultaneous moderate intensity AEx and cognitive training]) delivered in a synchronous, telerehabilitation format in comparison to AEx only and attention control (stretching) on cognition and aerobic fitness in older adults with SCD. First, we hypothesized that the exergame intervention would improve fluid (global) cognition and executive function to a greater extent relative to AEx only and attention control. Secondly, we hypothesized that exergame participants would improve aerobic fitness similarly as AEx-only participants.

Method

Design

This study was a Stage 1B trial according to the NIH Stage Model (NIA, 2023), used a 3-parallel group design, and randomized 39 participants to 3-month supervised exergame, AEx, or stretching control on a 2:1:1 allocation ratio. Randomization, which was concealed electronically through Research Electronic Data Capture (REDCap) randomization module, was stratified by age (<75 and ≥75 years) using random permuted blocks of 4 and 8. Group assignment was concealed from all investigators and data collectors, except for the statistician who generated the randomization sequence. Informed consent was received from participants via e-Consent, administered through REDCap, which has been validated as compliant with FDA 21 CFR Part 11 (Harris et al., 2009, 2019). This study complied with current ethical regulations for research (Harriss et al., 2019) and was approved by the University of Minnesota Institutional Review Board (IRB: # 1610M98324). Details of the trial protocol (NCT04311736; Salisbury, Plocher, et al., 2021) and data regarding its implementation and feasibility have been previously published (Salisbury et al., 2023).

Setting

Three screening visits were conducted over phone or virtually via Zoom. Baseline and 12-week data collections for main outcome variables were conducted on the university campus. Initially, the intervention was to be supervised directly in person; however, the delivery was changed to a telerehabilitation format due to the COVID-19 pandemic. Therefore, all exercise sessions (after an initial session, in-person familiarization) were conducted in participant’s place of residence, supervised virtually by the study interventionists using a synchronous telerehabilitation format (Zoom video).

Participants

To be enrolled in the Exergame Study, participants had to meet the research criteria of having SCD by Jessen et al. (2014), which included: (1) presence and worsening of SCD indicated by answering yes to both, “Do you perceive memory or cognitive difficulties?” and “In the last two years, has your cognition or memory declined?”; (2) no evidence of objective cognitive impairment denoted by a score of >26 on the Telephone Instrument for Cognitive Status (TICS; Seo et al., 2011); (3) absence of a clinical diagnosis of mild cognitive impairment or dementia; and (4) absence of evidence suggesting that chemical dependency, neurological condition, or an uncontrolled or major psychiatric disorder were the likely cause of SCD. In addition, participants were required to be English-speaking, ≥65 years of age, and community dwelling. The exclusion criteria were (1) current participation in an intervention study, (2) physically active (i.e., currently physically active ≥30 min continuously of moderate intensity activity [brisk walk] on ≥3 days per week), and (3) an American College of Sports Medicine (ACSM) exercise contraindication (ACSM, 2018).

Intervention

After completing baseline data collection, participants were enrolled and randomized. Participants completed a 1 session on-boarding period (familiarization) where the study interventionist delivered all necessary equipment to the participants’ home and helped facilitate any necessary set-up (Zoom access, BrainFitRx access, etc.). Each of the three groups was then prescribed three weekly sessions facilitated by the study interventionist using a synchronous telerehabilitation format (Zoom) for 3 months (36 total sessions).

Aerobic exercise

The AEx intervention was conducted on recumbent stationary cycles (Exerpeutic 900SL; Industry, CA) as described previously (Salisbury et al., 2023) To increase the translation potential of the exergame intervention to real life, laboratory-based, cycling-based cardiopulmonary exercise test was not conducted for prescribing moderate intensity. Instead, intensity was prescribed using rating of perceived exertion (RPE) on Borg Category Ratio-15 (6–20) RPE Scale (Borg, 1998). The exercise prescription alternated between progressing by intensity and duration. The week 1 (sessions 1–3) exercise prescription was set at an RPE of 11–12 for 30–35 min in session 1, which was increased by or 1-point on Borg (week 2 [sessions 4–6]) and then by 5 min (week 3 [sessions 7–9]) until the participant was able to exercise at moderate intensity (RPE of 12–14) for 50 min a session.

Exergame

Participants in the exergame group performed aerobic cycling as described in the AEx protocol while engaging in cognitive training for the duration of cycling. Duration was matched to the duration of the AEx and stretching control groups. The cognitive training exergame (BrainFitRx; Moai Technologies, L.L.C.; Maple Grove, MN) was housed on either an Apple TV or iPADs (Apple Inc.; Cupertino, CA). Participants used an Xbox-360 controller (Microsoft Corporation; Redmond, WA) to navigate through any of three potential virtual worlds to reach destinations to unlock and participate in cognitive games (training). Each of the three virtual worlds contained cognitive training consisting of 9–10 different cognitive task scenarios, each with 10 levels of difficulty (Figure 1). The cognitive training was progressed at the individual level based on performance in a specific cognitive game/task. Cognitive tasks in the BrainFitRx reflect tasks that are considered to have high ecological validity (Temprado, 2021) and mimic tasks seen in activities of daily living (i.e., memorizing grocery list, subsequent grocery shopping, etc.).

Figure 1.

Figure 1.

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(A–C) BrainFitRx Exergame System.

Attention control

Participants in the attention control group performed flexibility exercises that we had previously tested (Salisbury, Mathiason, et al., 2021). Sessions were prescribed as light intensity (RPE ≤9) stretching exercises including seated static stretches and range of motion movements.

Main Outcomes and Measures

Cognition

The primary outcome, objective neurocognitive functioning, was measured using the NIH Toolbox Cognition Domain (NIHTB-CB; Version 1.21; Weintraub et al., 2013) at baseline and 12-weeks. The NIH Toolbox is a series of computer-based tests that can be administered in approximately 45 min, has been validated and normed in individuals age 3 to 85, and has minimal floor and ceiling effects (Weintraub et al., 2013). The tests provide age-standardized scores for a Fluid Cognition Composite Score (consisting of executive function, processing speed, working memory, episodic memory, and attention) where fluid cognition is believed to be more adaptable to exercise and other lifestyle interventions compared to crystallized cognition (Hillman et al., 2008).

Aerobic fitness

Shuttle walk test

The shuttle walk test (SWT) was administered following the guidelines by Singh et al. (1992). Briefly, participants were instructed to walk a distance of 10 m around a marking between two cones, placed 0.5 m from each endpoint. Assistive devices were permitted. The test was finished when the participant was not able to maintain the required speed (more than 0.5 m from the cone). Laps were recorded and distance walked in meters was calculated. The SWT is considered a reliable test of aerobic fitness in older adults with multiple chronic conditions (intraclass correlation coefficient [ICC] 0.91–0.97; Wilkinson et al., 2019).

6-Minute walk test

Participants completed the 6-minute walk test (6MWT) according to American Thoracic Society guidelines (ATS, 2002). Briefly, participants were instructed to walk as far as they could in 6 min. Assistive devices and rest were permitted, running and jogging were not. The number of laps completed was quantified and used in the calculation of peak walking distance. The reliability of 6MWT is considered a reliable test of aerobic fitness in older adults with multiple chronic conditions (Steffen et al., 2002).

Statistical Analysis

To describe the sample and examine associations between each baseline measure and treatment group, we obtained descriptive statistics by group and conducted bivariate statistical tests (i.e., Welch’s F test and Fisher-Freeman-Halton’s test of association) in Statistical Package for Social Sciences (SPSS). To assess intervention effects, for each intervention outcome, we estimated linear mixed models having fixed effects of group, time, and the group-by-time interaction, with F tests used to assess these effects. An unstructured specification was used for the variance-covariance matrix, which we estimated for each group without imposing group equality constraints. For these models, we focused on the baseline to week 12 mean change for each group, and tested for differential change across groups, which we obtained through model contrasts. To further characterize the mean change across time, we computed the Cohen’s d effect size by dividing the group mean change across time by the baseline standard deviation for a given group. The mixed models were implemented with SAS PROC MIXED (version 9.4), with parameters obtained by restricted maximum likelihood estimation and the Kenward–Roger correction. Intent-to-treat analysis was used for all analyses, and alpha was set at 0.05 for each test.

To assess statistical power, we used SAS (PROC POWER and PROC GLMPOWER) to determine the minimum detectable Cohen’s d effect size that would achieve power ≥0.80 for the test of the (a) mean change from baseline to 12 weeks for each treatment group and (b) group-mean difference in this change. For the exergame, AEx, and stretching groups (exergame, n = 20; AEx, n = 10; and stretching, n = 8), Cohen’s d of 0.67, 1.0, and 1.16, respectively, achieves power ≥0.80, for the baseline to week 12 mean difference for a given outcome. For the contrast in the mean change across time between the exergame and each of the other groups, Cohen’s d of approximately 1.1 achieves power ≥0.80, whereas a Cohen’s d value of 1.41 is needed to attain ≥0.80 for the contrast between the AEx and stretching groups. Note that for these power analyses, we set alpha (two-tailed) at 0.05 and the baseline to 12-week correlation at 0.5.

Results

Participant Characteristics

Potential participants were screened by phone (screening 1; n = 229), virtual/Zoom (screening 2; n = 94), medical clearance (screening 3; n = 49), and exercise testing (baseline; n = 39). Thirty-nine met eligibility criteria and were enrolled: 20 randomized to exergame, 11 to cycling only, and 8 to stretching (Figure 2). The attrition rate at 3 months was 10.8% (15% exergame vs 10% AEx vs 0% stretching). Of note, all attritions in the exergame group (n = 3) were attributed to the government-mandated COVID-19 shutdown in March 2020, where participants were unable to complete 12-week assessments. The average age of the study sample (n = 39) was 74.6 (7.4) years and 69% were female. Their average TICS was 34.4 (2.4) and 97.4% were non-Hispanic White with an average of 17.7 (2.3) years of education (Table 1).

Figure 2.

Figure 2.

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The Exergame Study consort diagram.

Table 1.

Demographic and Clinical Variables

Variables Total (n = 38) Exergame (n = 20) Cycling (n = 10) Stretching (n = 8) p Value
Mean (SD)
Age (years) 74.6 (7.4) 74.7 (7.6) 75.8 (8.9) 72.6 (4.3) .51
Age of SCD onset (years) 69.8 (7.5) 69.9 (7.4) 71.4 (10.6) 67.3 (6.2) .53
SCD total score (MyCog) 7.2 (3.8) 6.1 (4.1) 9.0 (3.5) 8.1 (2.5) .17
TICS 34.4 (2.4) 35.1 (2.2) 34.3 (1.3) 33.0 (3.1) .12
GDS 2.21 (1.96) 2.45 (2.28) 1.60 (1.35) 2.38 (1.76) .53
Gas-10 2.76 (2.03) 2.50 (2.16) 3.40 (1.78) 2.63 (2.07) .52
BAI 2.95 (2.81) 2.70 (2.27) 3.30 (3.71) 3.13 (3.23) .85
Years of education 17.7 (2.3) 17.5 (2.8) 17.8 (1.7) 17.9 (2.0) .93
Number of medications 3.5 (2.4) 4.2 (2.9) 2.6 (1.4) 3.3 (1.8) .15
 Number (percentage %) with characteristic
Sex (% female) 26 (68.6) 11 (55.0) 9 (90.0) 6 (75.0) .15
Race (% Caucasian) 37 (97.4) 20 (100) 9 (90.0) 8 (100) .47
SCD onset in past 5 years (% yes) 29 (76.3) 17 (85.0) 6 (60.0) 6 (75.0) .19
SCD predominant in memory domain (% yes) 11 (28.9) 5 (25.00) 4 (50.0) 2 (25.0) .62
SCD perceived worse than others (% yes) 6 (15.8) 4 (20.0) 1 (10.0) 2 (25.0) .75
SCD concern enough to ask provider (% yes) 17 (44.7) 9 (45.0) 3 (30.0) 4 (50.0) .67
Have 3 or more SCD + criteria (% yes) 24 (63.2) 13 (65.0) 6 (60.0) 5 (62.5) .99
Depressiona (% yes) 21 (55.3) 13 (65.0) 4 (40.0) 4 (50.0) .48
Heart disease (% yes) 11 (29.9) 8 (40.0) 2 (20.0) 1 (12.5) .36
TIA/stroke (% yes) 4 (10.5) 1 (5.0) 3 (30.0) 0 (0.0) .09
Anxietyb (% yes) 10 (26.3) 4 (20.0) 4 (40.0) 2 (25.0) .56
Depression or anxiety medication (% yes) 11 (28.9) 5 (25.0) 3 (30.00) 3 (37.5) .89
AD medication (% yes) — — — — —
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Notes: AD = Alzheimer’s disease; BAI = Beck’s Anxiety Inventory; Gas-10 = Geriatric Anxiety scale (10-item version); GDS = Geriatric Depression scale (short form); MyCog = SCD Questionnaire Part I (MyCog); SCD = subjective cognitive decline; TIA = transient ischemic attack; TICS = Telephone Instrument for Cognitive Status.

aPhysician diagnosed, nonmajor depressive disorder, considered by physician to be stable and not causative of reported SCD.

bPhysician diagnosed, considered by physician to be stable and not causative of reported SCD.

Adherence

Overall adherence in the Exergame Study was 85.6% over the course of the 12-week intervention. Of the total training sessions completed collectively by the exergame and AEx groups, 87.7% of sessions achieved the prescribed RPE targets (84.3% and 94.9% of sessions, respectively, for the exergame and AEx groups). The AEx group (97.0 [4.3] %) achieved significantly higher attendance than the exergame group (78.2 [4.4] %; p = .02), and average RPE achieved between the exergames (12.8 [0.6]) and AEx (13.0 [0.7]) groups was not significant (p = .14).

Cognitive Outcomes

Table 2 presents the results for each cognitive outcome. The effect of time was significant, F(1, 23.9) = 13.16, p = .001, for the Fluid Composite score, and significant within-group improvements were seen for the exergame, t(14.08) = 2.53, p = .024, d = 0.33, and AEx groups, t(7.74) = 2.93, p = .020, d = 0.21. For the other cognitive outcomes, no other effects or within-group changes were significant, although the Cohen’s d was relatively large for the AEx group for Flanker Inhibitory Control and Attention, t(8.89) = 2.23, p = .053, d = 0.63.

Table 2.

Linear Mixed Model Results of the Baseline to 12 Week Mean Change for the Cognitive Outcomes

Baseline Week 12 Difference Baseline to week 12 group comparisons
Groups M (SD) M (SD) MD (SE) d a Contrasts MD (SE) d
Dimensional change card sort test
Exergame 99.9 (8.0) 98.9 (5.6) −1.0 (1.7) −0.13 Exergame vs stretching −2.0 (2.3) −0.32
AEx 99.5 (8.6) 101.1 (10.4) 1.6 (2.3) 0.19 AEx vs stretching 0.6 (2.7) −0.07
Stretching 99.6 (3.8) 100.6 (4.6) 1.0 (1.5) 0.26 Exergame vs AEx −2.6 (2.9) −0.39
Flanker inhibitory control and attention test
Exergame 92.4 (9.2) 92.9 (7.3) 0.6 (1.7) 0.07 Exergame vs stretching 0.2 (2.6) 0.0
AEx 86.0 (11.8) 93.4 (6.0) 7.4 (3.3) 0.63 AEx vs stretching 7.1 (3.9) 0.56
Stretching 92.6 (6.0) 93.0 (2.8) 0.4 (2.0) 0.07 Exergame vs AEx −6.8 (3.7) −0.56
Fluid composite score
Exergame 88.1 (11.3) 91.8 (9.6) 3.7* (1.5) 0.33 Exergame vs stretching 2.1 (2.1) 0.07
AEx 86.6 (14.3) 89.6 (13.2) 3.0* (1.0) 0.21 AEx vs stretching 1.4 (1.8) −0.05
Stretching 91.1 (6.1) 92.8 (6.6) 1.6 (1.4) 0.26 Exergame vs AEx 0.7 (1.8) 0.07
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Notes: AEx = aerobic exercise only; MD = mean difference.

a d = Mean difference between the 12 week and baseline periods divided by a given group’s baseline SD.

*p < .05.

Aerobic Fitness Outcomes

Table 3 presents the result for the fitness outcomes. For the SWT, the effects of group, F(1, 14.4) = 0.81, p = .384, time, F(1, 17.4) = 1.00, p = .331, and the group-by-time interaction, F(1, 17.4) = 0.19, p = .667, were not significant. There were also no significant within-group changes, as the Cohen’s d estimates were relatively small, with each group d < 0.15. For the 6MWT, the effect of time was significant, F(1, 10.5) = 6.26, p = .030. However, the specific within-group changes were relatively small to moderate in size, and the within-group changes were not significant for the exergame, t(12.08) = 2.11, p = .056, d = 0.16, or AEx groups, t(7.00) = 1.75, p = .123, d = 0.31.

Table 3.

Linear Mixed Model Results of the Baseline to 12 Week Mean Change for the Aerobic Fitness Outcomes

Baseline Week 12 Difference Baseline to week 12 comparisons
Groups M (SD) M (SD) MD (SE) d a Contrasts MD (SE) d
Shuttle walk test (m)
Exergame 255.5 (105.1) 263.4 (131.6) 8.0 (23.7) 0.08 Exergame vs AEx −12.4 (28.3) −0.05
AEx 298.4 (153.3) 318.7 (151.9) 20.4 (15.5) 0.13 — — —
Six-minute walk test (ft)
Exergame 1,334.5 (427.1) 1,404.5 (423.5) 70.0 (33.1) 0.16 Exergame vs AEx −49.0 (75.5) −0.15
AEx 1,475.5 (383.6) 1,594.4 (427.8) 119.0 (67.9) 0.31 — — —
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Notes: AEx = aerobic exercise only; MD = mean difference.

a d = Mean difference between the 12 week and baseline periods divided by a given group’s baseline SD.

Discussion

Our primary hypothesis was that the exergame intervention would improve fluid (global) cognition and executive function to a greater extent relative to AEx only and attention control. This hypothesis was partially supported, as the change scores for fluid cognition were superior for the exergame versus AEx group, with both showing significant within-group changes. However, the between-group changes were nonsignificant. The findings from this study agree with those published in meta-analysis suggesting that exergame has the ability to enhance cognitive function and therefore may be an important strategy for active aging, particularly for people at risk for cognitive impairment (Yen & Chiu, 2021). Interestingly, the exergame did not have a strong (or significant) effect on executive function, which did not support the primary hypothesis of the study. This was surprising given that executive function is believed to be the cognitive domain considered to be most adaptable to exercise and cognitive training (Chen et al., 2020).

Direct comparisons to other combined exercise and cognitive training (including exergame) studies are challenging given the heterogeneity of the exercise modalities, intensities employed, and the cognitive training involved. Torres and colleagues have begun a classification system for defining different types of exercise-cognitive training to help address this heterogeneity (Torre & Temprado, 2021). The three-level classification system includes: (1) physical-cognitive training (i.e., combination of cognitive training with aerobic) and/or resistance training; (2) motor-cognitive training (i.e., combination of complex motor skills training and additional cognitive training); and (3) multidomain training (i.e., combination of physical + motor + cognitive training). To our knowledge, only three other physical-cognitive exergame studies have been conducted in older adults. Two studies employed a “cyber-cycle” system, which allowed participants to move on a 3D virtual bike tour where participants were asked to navigate a virtual environment while performing aerobic cycling (Anderson-Hanley et al., 2012; Barcelos et al., 2015). In the third study of an interactive physical and cognitive exercise system (“iPACES system”), participants were instructed to learn a list of neighborhood errand locations, pedal along a scenic pathway, choose the correct location at each fork in the road, and then retrace the same path (Anderson-Hanley et al., 2018). Overall, the exergame systems conducted at low intensity (intensity adherence not reported in the “iPACES” study) over a 12-week period improved measures of executive function compared to a cognitive-training-only control (Anderson-Hanley et al., 2018), cycling only control (Anderson-Hanley et al., 2012), or low cognitive demand cycling group (Barcelos et al., 2015).

We believe that the successful delivery of moderate intensity, continuous AEx achieved in the exergame group is important to point out. Mechanistically, it is believed that the sustained moderate-intensity AEx is a metabolically demanding promoter for the release of muscle-derived neurotrophic factors (Tari, Norevik et al., 2019), which are believed to be released in an intensity-dependent manner (Reycraft et al., 2020). Circulating neurotrophic factors are then delivered to the brain because of exercise-induced increases in cerebral blood flow (Barnes & Corkery, 2018). Therefore, the AEx acts as a primer to the brain for the concurrent cognitive training, which directly targets cognition and promotes a synergistic effect on neuroplasticity (Tari, Norevik et al., 2019; Torre & Temprado, 2021). Additionally, the successful completion of the moderate-intensity AEx prescription promotes the achievement of the current guidelines of 150 min per week of moderate intensity physical activity, recommended for the reduction of AD/ADRD risk factors and other chronic diseases (Piercy et al., 2018).

To our knowledge, no study implementing a simultaneous-delivered physical-cognitive training exergame has evaluated effects on 6MWT and SWT. However, non-exergame, physical-cognitive training delivered in a sequential manner has consistently produced favorable effects on physical fitness as indicated by improvements in 400-m walk time (Legault et al., 2011), estimated peak oxygen consumption from the 2-km walk test (Linde & Alfermann, 2014), and SWT (Shah et al., 2014). Although there were no significant between-group differences regarding the mean baseline to week 12 change in our sample, the exergame group adjusted 12-week changes for the 6MWT was 21.3 m, which represents a meaningful change in older adults (Perera et al., 2006). This suggests that the exergame does not detract from the ability for the participant to receive quality AEx in order to promote a meaningful change in their aerobic fitness, supporting the study’s secondary hypothesis. Interestingly, in the exergame group, change in the Flanker Inhibitory Control and Attention test showed a weak-moderate correlation with change in 6MWT (r = 0.44; p = .15), whereas the AEx group showed a weak correlation between change in Dimensional Change Card Sort test and change in SWT (r = 0.30; p = .47). These positive associations add to the evidence showing the importance of CRF as a moderating factor in cognitive changes. Support for this has been provided by the large population-based HUNT study (Tari, Naumann et al., 2019), where a subcohort of 320 adults were followed over 7.6 years. Participants who had improved their estimated CRF from baseline over time with each 1-metabolic equivalent of task (MET [estimate of CRF]) increase in CRF reduced their risk of dementia by 16%. After a follow-up time of 19.6 years, each 1-MET improvement reduced the risk by 10%. To date, associations between changes in CRF and cognitive reserve in persons at risk for AD are understudied. In 101 cognitive unimpaired older adults, the magnitude of change in CRF, following an AEx intervention was strongly correlated (β = 2.30 [0.71]; p < .01) with performance in cognitive tasks (Vidoni et al., 2015).

As reported previously, the telerehabilitation exergame delivery was both feasible and safe, as indicated by high attendance and adherence to the exercise prescription and low adverse events (Salisbury et al., 2023). However, the synchronous, audiovisual delivery of the exergame telerehabilitation program has direct clinical relevance. Specifically, we believe that this is the first study that has investigated the effects of exergame telerehabilitation in persons with SCD, a population with significantly higher risk for future development of mild cognitive impairment and dementia (Mendonça et al., 2016). Although not directly assessed in this study, exergaming is generally considered more enjoyable and preferred to exercise alone (McDonough et al., 2018). Therefore, exergaming could represent a more engaging and fun mode of physical activity that can help older adults with greater ADRD risk reduce their sedentary time, while enhancing fluid cognition. Equally important, the telerehabilitation delivery represents a potential to increase the access to therapy in structurally weak areas, where appropriate healthcare structures and offers are missing.

The predominant weakness of this study was that our study was limited by its design as a Stage 1B trial with a small sample size, which contributed to our inability to detect significant between-group differences. The purpose of Stage 1B trials is to pilot test an intervention, so the findings are preliminary (NIA, 2023). However, there have been few studies that evaluated the preliminary effects of a physical-cognitive-focused exergame on cognition and CRF, so Stage 1B trials are appropriate and it is premature to conduct a fully powered trial without first testing the exergame intervention in a pilot study. The Exergame Study was conducted for the majority of its time during the COVID-19 pandemic, which affected recruitment/enrollment and some data collection, although the telerehabilitation delivery was relatively unaffected. Although depression and anxiety, which can affect cognitive performance, were screened thoroughly at baseline, it is possible that family/life changes induced by COVID-19 during the Exergame Study intervention phase may have influenced anxiety and depressive symptoms, not evidenced at the baseline phase. As a result, this may influence cognitive testing at the 12-week posttesting. Lastly, the generalizability of the findings may be affected by the lack of a diverse sample, as it was 100% non-Hispanic White.

There are several strengths to the study that should be mentioned. First, the Exergame Study included a rigorous design and implementation following clinical trial guidelines with interventionist-supervised exercise delivery, which promoted high attendance and adherence to the protocols. Secondly, the BrainFitRx exergame utilizes ecologically valid and cognitively challenging cognitive games (Temprado, 2021), while implementing an AEx program that follows gold standard ACSM guidelines for improving aerobic fitness in older adults (ACSM, 2018). Currently, most “exergame” studies have tested “off the shelf” exergame (Nintendo Wii, etc.) or free “cognitively interactive games” (mental leisure activities [Sodoku, etc.]), which typically (1) disregard industry standard practices of exercise prescription, (2) lack proper theoretical founding concepts or cognition influence, and (3) lack game scenarios that are tailored to older adults and do not focus on cognitive domains or demands (Temprado, 2021). Lastly, this study employed gold standard, clinically utilized field tests of aerobic fitness (SWT and 6MWT), where the majority of studies that have focused on cognitive effects of “laboratory-produced” exergames (Anderson-Hanley et al., 2012, 2017, 2018) have failed to assess changes in aerobic fitness, which is a hypothesized mediator in cognitive gains (Tari, Norevik et al., 2019).

Conclusion

Exergame delivered through the BrainFitRx system significantly improved fluid cognition and its effect was stronger compared to AEx or stretching control group, indicating a potential synergistic effect from AEx and cognitive training. The aerobic fitness changes were similar between the exergame and AEx-only groups, indicating that the feasibility of adding cognitive training to AEx concurrently without sacrificing gains in aerobic fitness from AEx. This finding is significant because aerobic fitness has been supported as a physiological mechanism for cognitive gains. Further controlled studies with greater sample size and greater diversity are required to expand the results of this study.

Acknowledgments

The authors thank the participants, their family members, and the study staff of the Exergame Study.

Contributor Information

Dereck L Salisbury, School of Nursing, University of Minnesota, Minneapolis, Minnesota, USA.

Keenan A Pituch, Edison College of Nursing and Health Innovation, Arizona State University, Phoenix, Arizona, USA.

Fang Yu, Edison College of Nursing and Health Innovation, Arizona State University, Phoenix, Arizona, USA.

Funding

This work was supported by a Small Business Innovation Research award from the National Institute on Aging of the National Institutes of Health [4R44AG055176-02].

Conflict of Interest

None.

Data Availability

Data sharing is available upon reasonable request with the corresponding author. This study was not preregistered.

Author Contributions

Study concept and design, D. L. Salisbury and F. Yu; acquisition of subjects and/or data, analysis and interpretation of data, D. L. Salisbury, K. A. Pituch, and F. Yu; preparation of manuscript, D. L. Salisbury, K. A. Pituch, and F. Yu.

Sponsor Role

The sponsor had no role in the design, methods, subject recruitment, data collections, analysis, and preparation of paper. The content is solely the responsibility of the authors and does not necessarily present the official review of the National Institutes of Health.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Data sharing is available upon reasonable request with the corresponding author. This study was not preregistered.

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