Kohei Sakaki
email: kohei.sakaki@tohoku.ac.jp

Rui Nouchi

Yutaka Matsuzaki
email: yutaka.matsuzaki.e5@tohoku.ac.jp

Toshiki Saito
email: toshiki.saito.e1@tohoku.ac.jp

Jérôme Dinet
email: jerome.dinet@univ-lorraine.fr

Ryuta Kawashima

R.N K S Conceptualization

R K ; Methodology

R K ; Visualization

Benefits of VR Physical Exercise on Cognition in Older Adults with and without Mild Cognitive Decline: A Systematic Review of Randomized Controlled Trials

Keywords: virtual reality, cognitive function, cognitive declines, physical intervention, older adults

It is well known that physical exercise has beneficial effects on cognitive function in older adults. Recently, several physical exercise programs with virtual reality (VR) have been proposed to support physical exercise benefits. However, it is still unclear whether VR physical exercise (VR-PE) has positive effects on cognitive function in older adults. The purpose of this study was to conduct a systematic review (SR) of the effects of VR-PE on cognitive function in older adults with and without cognitive decline. We used academic databases to search for research papers. The criteria were intervention study using any VR-PE, participants were older adults with and without mild cognitive decline (not dementia), and cognitive functions were assessed. We found that 6 of 11 eligible studies reported the significant benefits of the VR-PE on a wide range of cognitive functions in aging populations. The SR revealed that VR-PE has beneficial effects on the inhibition of executive functions in older adults with and without mild cognitive decline. Moreover, VR-PE selectively leads to improvements in shifting and general cognitive performance in healthy older adults. The SR suggests that VR-PE could be a successful approach to improve cognitive function in older adults with and without cognitive decline.

Introduction

Cognitive function declines with age [START_REF] Wilson | Normative Cognitive Decline in Old Age[END_REF]. This decline is an indicator of lower wellbeing [START_REF] Yagi | The Role of Cognitive Control in Age-Related Changes in Well-Being[END_REF] and a risk of dementia in the future [START_REF] Jongstra | Improving Prediction of Dementia in Primary Care[END_REF][START_REF] Xie | Predictors of future cognitive decline in persons with mild cognitive impairment[END_REF]. Considering the growth of the older adult population, it is important to delay or prevent dementia in healthy older adults and older adults with mild cognitive decline [START_REF] Livingston | Dementia prevention, intervention, and care: 2020 report of the Lancet Commission[END_REF]. Physical exercise (PE) plays an important role in maintaining and improving cognitive function in the aging population [START_REF] Guure | Impact of Physical Activity on Cognitive Decline, Dementia, and Its Subtypes: Meta-Analysis of Prospective Studies[END_REF]. A previous cohort study has reported that physical exercise reduces dementia risk in older adults [START_REF] Larson | Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older[END_REF]. Previous intervention studies have reported that physical exercise programs using aerobic exercise [START_REF] Hsu | Aerobic exercise promotes executive functions and impacts functional neural activity among older adults with vascular cognitive impairment[END_REF][START_REF] Formenti | Acute Effect of Exercise on Cognitive Performance in Middle-Aged Adults: Aerobic Versus Balance[END_REF], balance exercise [START_REF] Formenti | Acute Effect of Exercise on Cognitive Performance in Middle-Aged Adults: Aerobic Versus Balance[END_REF], combination physical exercises [START_REF] Nouchi | Four weeks of combination exercise training improved executive functions, episodic memory, and processing speed in healthy elderly people: Evidence from a randomized controlled trial[END_REF][START_REF] Nouchi | A Single 30 Minutes Bout of Combination Physical Exercises Improved Inhibition and Vigor-Mood in Middle-Aged and Older Females: Evidence From a Randomized Controlled Trial[END_REF], or cardiovascular and coordination training [START_REF] Voelcker-Rehage | Cardiovascular and Coordination Training Differentially Improve Cognitive Performance and Neural Processing in Older Adults[END_REF] have acute and long-term benefits on cognitive functions.

Although these previous studies have demonstrated the beneficial effects of physical exercise on cognitive functions, a large proportion of the aging population does not participate in adequate physical exercise [START_REF] Haskell | Physical activity and public health: Updated recommendation for adults from the American College of Sports Medicine and the American Heart Association[END_REF]. There are external and internal barriers for older adults to participate in physical exercise [START_REF] Justine | Barriers to participation in physical activity and exercise among middle-aged and elderly individuals[END_REF]. For example, older adults have reported that the "lack of infrastructure" is one of the main external barriers and "lack of motivation" one of the main internal barriers [START_REF] Justine | Barriers to participation in physical activity and exercise among middle-aged and elderly individuals[END_REF].

Recent technologies, such as the virtual reality (VR) technique, are expected to support physical exercise in the aging population. VR is defined as the simulation, in real time, of an interactable environment, scenario, or activity [START_REF] De Bruin | Use of virtual reality technique for the training of motor control in the elderly[END_REF]. Several VR physical exercises (VR-PE) have been proposed [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Anderson-Hanley | 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[END_REF][START_REF] Bacha | Effects of Kinect Adventures Games Versus Conventional Physical Therapy on Postural Control in Elderly People: A Randomized Controlled Trial[END_REF][START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF][START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF][START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF][START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF], in which people at their homes use commercially available VR systems, such as video gaming consoles or personal computers [START_REF] De Bruin | Use of virtual reality technique for the training of motor control in the elderly[END_REF]. These products can help to overcome the barriers of lack of infrastructure and motivation since almost all VR-PE include gaming factors to enhance motivation and increase user participation [START_REF] Holden | Use of virtual environments in motor learning and rehabilitation[END_REF]. Previous studies have shown that physical exercise with VR has the potential to increase exercise behavior in older adults [START_REF] Van Schaik | Virtual Augmented Exercise Gaming for Older Adults[END_REF].

Previous intervention studies using gaming factors showed significant improvements in a wide range of cognitive functions and a small dropout ratio from the intervention in older adults [START_REF] Nouchi | Brain Training and Sulforaphane Intake Interventions Separately Improve Cognitive Performance in Healthy Older Adults, Whereas a Combination of These Interventions Does Not Have More Beneficial Effects: Evidence from a Randomized Controlled Trial[END_REF][START_REF] Nouchi | Newly Developed TV-Based Cognitive Training Games Improve Car Driving Skills, Cognitive Functions, and Mood in Healthy Older Adults: Evidence From a Randomized Controlled Trial[END_REF][START_REF] Nouchi | Small Acute Benefits of 4 Weeks Processing Speed Training Games on Processing Speed and Inhibition Performance and Depressive Mood in the Healthy Elderly People: Evidence from a Randomized Control Trial[END_REF][START_REF] Nouchi | Brain training game improves executive functions and processing speed in the elderly: A randomized controlled trial[END_REF]. It is also reported that VR-PE led to improvements both in cognitive function in healthy older adults [START_REF] Anderson-Hanley | 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[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF][START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF] and older adults with cognitive decline [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF]. Therefore, it seems possible to use VR-PE to enhance cognitive function in older adults. However, to the best of our knowledge, there is no systematic review (SR) and metaanalysis of RCTs to assess the benefits of VR-PE on cognitive function in older adults with or without mild cognitive decline (not dementia). Therefore, we aimed to conduct a systematic review of the beneficial effects of VR-PE on cognition.

Materials and Methods

Protocol and Registration

This protocol followed the statement and general principles of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [START_REF] Moher | Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement[END_REF] (Supplementary Table S1), and it was designed using the International Prospective Register of Systematic Reviews (PROSPERO) with the registration number CRD42020220020 (https://www.crd.york.ac. uk/prospero/display_record.php?RecordID=220020 (accessed on 10 December 2020)).

Search Strategy

Our review question was "does VR-PE have the effect of improving cognitive functions in older adults with and without mild cognitive declines?". We searched PubMed and Scopus for studies using specific search terms (Supplementary Table S2). Only articles published in English were included, and their publication period was unrestricted.

Inclusion and Exclusion Criteria

This SR included studies where participants were men and women aged 60 years or older with and without mild cognitive decline. Participants with a current diagnosis of Alzheimer's disease, dementia, vascular dementia, stroke, head injury, depression, or other neurologic disorders were excluded. Only intervention studies to assess the beneficial effects of VR-PE on cognitive function were included. We defined VR as the simulation, in real time, of an interactable environment, scenario, or activity [START_REF] De Bruin | Use of virtual reality technique for the training of motor control in the elderly[END_REF]. There were no restrictions on which type of VR device could be used for intervention. The eligible outcomes were cognitive functions measured using any validated measure, including computerized tests. Cognitive functions, including general cognitive functions, executive function, working memory capacity/short-term memory, episodic (long-term) memory, processing speed, and attention, among others, were considered in this SR.

Quality Assessment

The quality of each study was assessed using the modified Delphi list [START_REF] Verhagen | The Delphi list: A criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus[END_REF]. These quality assessment criteria were based on previous systematic review papers [START_REF] Nouchi | Improving Cognitive Function from Children to Old Age: A Systematic Review of Recent Smart Ageing Intervention Studies[END_REF][START_REF] Nouchi | Effects of Lutein and Astaxanthin Intake on the Improvement of Cognitive Functions among Healthy Adults: A Systematic Review of Randomized Controlled Trials[END_REF].

Results

Study Selection and Characteristics

Overall, 412 scientific articles were identified through database searches. After excluding duplicates (n = 36), we identified 376 articles. At the title and abstract screening, we excluded 352 studies that were not intervention studies, did not assess cognitive functions as an outcome, or intended to treat physical, cognitive, or mental diseases. Of the 24 articles selected for full-text assessment, 13 were excluded for including clinical patients who suffered from physical or cognitive disorders (n = 4) or young adults (n = 2), case reports (n = 2), secondary analysis (n = 2), one-shot intervention (n = 1), no cognitive assessments (n = 1), or full-text unavailable (n = 1). Eleven articles were eligible for the current review, based on the inclusion and exclusion criteria. The study selection process is presented in the PRISMA flowchart (Figure 1). The characteristics of the included studies are summarized in Table 1. Six studies included healthy older adults [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Bacha | Effects of Kinect Adventures Games Versus Conventional Physical Therapy on Postural Control in Elderly People: A Randomized Controlled Trial[END_REF][START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF][START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF], and five included older adults with mild cognitive decline (mild cognitive impairment [MCI] or mild dementia) [START_REF] Anderson-Hanley | 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[END_REF][START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF][START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF]. The sample size ranged from 10 to 84. The mean age of the participants ranged from 68.0-87.2 years.

Quality Assessment

The methodological quality of the included studies is shown in Table 2. The range of the quality assessment score was 6-12, with an average of 8.1 (SD = 2.02).

? ? Y N N N N Y N 6 Liao; 2020; Taiwan Y Y Y Y Y N N Y N N Y Y Y N 9 Monteiro-Junior; 2017; Brazil Y ? Y Y ? N Y N N N Y Y Y N 7
Park Eight studies fulfilled the requirements of Item 11 (adequate description of the control/comparison group) [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Anderson-Hanley | 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[END_REF][START_REF] Bacha | Effects of Kinect Adventures Games Versus Conventional Physical Therapy on Postural Control in Elderly People: A Randomized Controlled Trial[END_REF][START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF][START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF][START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF]. Seven of eight studies used the physical exercise only group as the control group [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Anderson-Hanley | 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[END_REF][START_REF] Bacha | Effects of Kinect Adventures Games Versus Conventional Physical Therapy on Postural Control in Elderly People: A Randomized Controlled Trial[END_REF][START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF][START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF]. Two studies used the physical and cognitive exercise group as the control group [START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF][START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF]. The other three studies used a no-intervention group as the control group [START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF].

The scores of Item 2 (Treatment Allocation Concealed), Item 5 (Blinded Outcome Assessor), Item 6 (Care Provider Blinded), Item 7 (Patient Blinded), Item 9 (intention-to-treat analysis), Item 10 (details of random allocation methods), and Item 14 (reporting CONSORT statement) were low. It seems to be difficult to blind participants and caregivers on the type of intervention they received because of the nature of the intervention methods. Thus, only five studies used blinded outcome assessors.

Intervention

The characteristics of intervention methods in the included studies are summarized in Table 3. The intervention period of the included studies was six-weeks-six-months. Three studies were conducted for six months [START_REF] Anderson-Hanley | 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[END_REF][START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF], two studies were conducted for three months [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF], one study was conducted for eight weeks [START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF], one study was conducted for seven weeks [START_REF] Bacha | Effects of Kinect Adventures Games Versus Conventional Physical Therapy on Postural Control in Elderly People: A Randomized Controlled Trial[END_REF], and four studies were conducted for six weeks [START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF][START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF]. Three studies used a stationary bike equipped with a VR display ("Cybercycle" or "Cycle-ergometer") as the method of VR-PE [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Anderson-Hanley | 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[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF]. One study used Kayak ergometers with 3-D images on the screen [START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF]. Five studies used a motion capture system ("Xbox 360 Kinect" or "Wii Fit") to provide feedback information on movements during physical exercise [START_REF] Bacha | Effects of Kinect Adventures Games Versus Conventional Physical Therapy on Postural Control in Elderly People: A Randomized Controlled Trial[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF][START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF]. Two studies used a pressure sensitive platform ("BioRescue" or "Impact Dance Platforms") to provide feedback information about steps or balance during physical exercise [START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF][START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF].

Outcome

Among the 11 studies, a variety of cognitive tests were used to examine the impact of the intervention on cognitive function. Some studies employed a general assessment measure, such as the Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA). Others combined multiple tests to assess a single cognitive domain. In this SR, the cognitive tests were divided into seven cognitive domains-general cognitive functions, executive function, working memory capacity/short-term memory, episodic (longterm) memory, processing speed, attention, and others-based on a previous study [START_REF] Nouchi | Improving Cognitive Function from Children to Old Age: A Systematic Review of Recent Smart Ageing Intervention Studies[END_REF]. The various psychological tests used to assess cognitive function in the included studies are summarized in Table 4.

General Cognitive Functions

Two general cognitive function outcomes were measured using the MMSE or MoCA in seven studies [START_REF] Bacha | Effects of Kinect Adventures Games Versus Conventional Physical Therapy on Postural Control in Elderly People: A Randomized Controlled Trial[END_REF][START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF][START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF][START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF][START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF]. The test of general cognitive functions performed for healthy older adults indicated a statistically significant improvement in MoCA compared to the control group [START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF][START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF]. Another study on healthy older adults [START_REF] Bacha | Effects of Kinect Adventures Games Versus Conventional Physical Therapy on Postural Control in Elderly People: A Randomized Controlled Trial[END_REF] and older adults with mild cognitive decline [START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF] showed a statistically significant improvement in MoCA from baseline. In contrast, one study of healthy older adults and two studies of older adults with mild cognitive decline reported no significant change in the MoCA score [START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF] or MMSE score [START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF].

Executive Function

Four cognitive domains (inhibition, shifting, updating, and the others) in executive function assessed by 12 tests (trail making test part B (TMT-B) [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF], color trails [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Anderson-Hanley | 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[END_REF], Stroop [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Anderson-Hanley | 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[END_REF], verbal fluency [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF], executive control task [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF], timed up and go test cognition (TUG-cog) [START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF], abstract thinking and judgment [START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF], animal name fluency [START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF], frontal assessment battery (FAB) [START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF], TUG dual attention task (TUG-DT) [START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF], executive interview 25 (EXIT-25) [START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF], floor maze test (FMT) [START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF]) were assessed in nine studies.

Inhibition measured by the Stroop test performed by healthy older adults indicated a statistically significant improvement compared to the control group [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF]. One study of older adults with mild cognitive decline showed statistically significant improvements in the Stroop test from baseline [START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF].

Shifting as measured by color trails performed by healthy older adults indicated statistically significant improvements compared to the control group [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF] but not in older adults with mild cognitive decline [START_REF] Anderson-Hanley | 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[END_REF]. TMT-B performed by healthy older adults indicated a statistically significant improvement from baseline [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF]. One study that performed TMT-B in older adults was excluded from the analysis because the number of participants who completed the task was too small [START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF].

Updating measured by the executive control task performed for healthy older adults indicated a statistically significant improvement from the baseline [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF]. Other studies performing verbal fluency or animal name fluency in healthy older adults [START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF] and in older adults with mild cognitive decline [START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF] did not indicate statistically significant improvements. Other types of executive function measures were used in six studies [START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF][START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF]. Dualtask performance during motor and cognitive tasks measured by TUG-cog performed by healthy older adults indicated statistically significant improvement compared to the control group [START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF] but not TUG-DT performed by older adults with mild cognitive decline [START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF]. Abstract thinking in the cognitive abilities screening instrument (CASI) [START_REF] Teng | The Cognitive Abilities Screening Instrument (CASI): A practical test for cross-cultural epidemiological studies of dementia[END_REF] performed by older adults with mild cognitive decline indicated statistically significant improvement compared to the control group [START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF]. FAB performed by older adults with mild cognitive decline did not indicate a statistically significant improvement [START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF]. EXIT-25 performed by older adults with mild cognitive decline indicated statistically significant improvements from the baseline [START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF]. The floor maze test performed by healthy older adults did not indicate a statistically significant improvement [START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF].

Working Memory Capacity and Short-Term Memory

Working memory capacity was assessed using the backward digit Span in four studies [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Anderson-Hanley | 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[END_REF][START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF]. One study that performed digit span backward in healthy older adults indicated statistically significant improvements compared to the control group [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF]. Additionally, one study performed in healthy older adults indicated statistically significant improvements from the baseline [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF]. In contrast, one study performed in healthy older adults [START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF] and in older adults with mild cognitive decline [START_REF] Anderson-Hanley | 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[END_REF] reported no significant change.

Two short-term memory outcomes were assessed using the digit span forward or the subtest of CASI in three studies [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF]. One study that performed digit span forward in healthy older adults indicated statistically significant improvements compared to the control group [START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF]. In contrast, one study performed in healthy older adults [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF] and in older adults with mild cognitive decline [START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF] reported no significant change.

Episodic (Long-Term) Memory

Verbal episode memory outcomes were assessed using the Rey auditory verbal learning test (RAVLT) [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF], ADAS word list [START_REF] Anderson-Hanley | 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[END_REF], logical memory (story recall) in WMS-R [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF], and Chinese version of the California verbal learning test (CVVLT) [START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF] in five studies. One study that performed the ADAS word list for older adults with mild cognitive decline indicated statistically significant improvement compared to the control group [START_REF] Anderson-Hanley | 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[END_REF]. Additionally, one study performing logical memory (story recall) in WMS-R for healthy older adults [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF] and one study performing CVVLT for older adults with mild cognitive decline [START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF] indicated a statistically significant improvement from the baseline but not RAVLT [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF].

Visual episode memory outcomes were assessed using the paired associates learning task [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF] or delayed recall [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF]. The paired associates learning task performed for healthy older adults indicated statistically significant improvements from the baseline [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF] but not in figure delayed recall [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF].

Processing Speed

Two processing speed outcomes were assessed using the trail making test part A (TMT-A) and digit symbol substitution task from Wechsler adult intelligence scale-revised (WAIS-R) in three studies [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF]. The tests of processing speed performed by healthy older adults indicated statistically significant improvements from the baseline [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF]. In contrast, one study performed in healthy older adults [START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF] and in older adults with mild cognitive decline [START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF] reported no significant change.

Attention

Four attention outcomes were assessed using a subtest of CASI (ATTEN), attentional matrices test, age concentration tests A and B, and letter digit symbol test in four studies [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF]. Only age concentration tests A and B performed by healthy older adults indicated statistically significant improvements from the baseline [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF], but this did not occur in three studies [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF].

Others

Visuospatial functions were assessed in two studies [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF]. Figure copy and clock performed by healthy older adults [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF] and the Rey-Osterrieth complex figure test performed by older adults with mild cognitive decline [START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF] did not indicate statistically significant improvements.

The ecological validity questionnaire, which is a self-report measure of cognitive function, was assessed in a study of older adults with mild cognitive decline and showed statistically significant improvements compared to the control group [START_REF] Anderson-Hanley | 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[END_REF].

Subdomains in the CASI (mental manipulation, orientation, language, drawing, longterm memory) performed by older adults with mild cognitive decline did not indicate statistically significant improvements [START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF].

Discussion

This study first conducted an SR to investigate the effects of VR-PE on cognitive functions in older adults with and without mild cognitive decline. Eleven studies (six studies including healthy older adults and five studies including older adults with mild cognitive decline) met the SR criteria [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Anderson-Hanley | 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[END_REF][START_REF] Bacha | Effects of Kinect Adventures Games Versus Conventional Physical Therapy on Postural Control in Elderly People: A Randomized Controlled Trial[END_REF][START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF][START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF][START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF][START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF]. We found that 6 of 11 studies (four studies for healthy older adults and two studies for older adults with mild cognitive decline) reported the significant benefits of VR-PE on general cognitive function [START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF][START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF], executive function [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF], working memory capacity [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF], short-term memory [START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF] and verbal episodic memory [START_REF] Anderson-Hanley | 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[END_REF] compared to the control groups.

In the SR, three of nine studies that assessed executive functions reported a significant improvement in executive functions in healthy older adults and older adults with mild cognitive decline compared to the control groups. These studies included diverse aspects of executive function, such as inhibition, shifting, updating, dual-task performance, and abstract thinking in older adults with and without mild cognitive decline. We discuss the effects of VR-PE on each subdomain in executive functions separately. For inhibition, VR-PE should have beneficial effects on inhibition performance in older adults with and without mild cognitive decline [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF]. For shifting, results indicate a potential beneficial effect of VR-PE on shifting performance as measured by trial making [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF] or color trials [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF] in healthy older adults. For the dual-task task, we found only two studies that measured dual-task performance [START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF][START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF] and one study that measured abstract thinking [START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF]. It is difficult to conclude the positive effects of VR-PE on dual-task and abstract thinking in executive functions. In future studies, it would be important to investigate the beneficial effects of VR-PE on dual-task and abstract thinking in older adults.

We found inconsistent results in general cognitive function, working memory capacity, short-term memory, and verbal episodic memory. For general cognitive function, two of seven studies indicate statistically significant improvement compared to the control group [START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF][START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF] but not the five studies [START_REF] Bacha | Effects of Kinect Adventures Games Versus Conventional Physical Therapy on Postural Control in Elderly People: A Randomized Controlled Trial[END_REF][START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF][START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF]. For working memory capacity and short-term memory, the result should be interpreted with limitations due to the small number of studies that assessed working memory capacity and short-term memory [START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF]. For verbal episodic memory, results indicate that VR-PE does not have positive effects on verbal memory performance in older adults with and without mild cognitive decline [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Anderson-Hanley | 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[END_REF][START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF][START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF].

It is important to consider the differences in the effects of VR devices on cognition among the included studies. Four types of VR devices were included in the studied papers: stationary bikes equipped with VR displays ("Cybercycle" or "Cycle-ergometer"), Kayak ergometers, motion capture ("Xbox 360 Kinect" or "Wii Fit"), and pressure-sensitive platforms ("BioRescue" or "Impact Dance Platforms"). We did not find any significant improvements when participants used pressure-sensitive platforms compared to the control group [START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF][START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF]. However, for motion capture, three of five studies reported significant improvements in abstract thinking and dual task performance in executive functions in healthy older adults [START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF] as well as older adults with mild cognitive decline [START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF] and in short-term memory in healthy older adults [START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF]. For the stational bike equipped with VR, one of two studies showed significant improvements in shifting and inhibition performance in executive functions in healthy older adults [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF]. Moreover, one study reported a pre-post difference in inhibition in older adults with mild cognitive decline [START_REF] Anderson-Hanley | 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[END_REF]. For the Kayak ergometers, one study showed significant improvements in general cognitive function in healthy older adults [START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF]. Taken together, the motion capture, stationary bike equipped with a VR display, and Kayak ergometers should be suitable VR devices to improve cognitive function.

A previous systematic review and meta-analysis suggested that sufficient cognitive challenges seemed important for a combined program of physical and cognitive activity [START_REF] Gheysen | Physical activity to improve cognition in older adults: Can physical activity programs enriched with cognitive challenges enhance the effects? A systematic review and meta-analysis[END_REF]. In our systematic review, we focused on the gaming factors which could enhance motivation rather than cognitive challenges of PE programs combined with VR devices. Not only the studies used VR-PE with cognitive challenges [START_REF] Anderson-Hanley | 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[END_REF][START_REF] Bacha | Effects of Kinect Adventures Games Versus Conventional Physical Therapy on Postural Control in Elderly People: A Randomized Controlled Trial[END_REF][START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF][START_REF] Eggenberger | Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF][START_REF] Liao | Using virtual reality-based training to improve cognitive function, instrumental activities of daily living and neural efficiency in older adults with mild cognitive impairment[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF] but also without high cognitive challenges [START_REF] Anderson-Hanley | Exergaming and older adult cognition: A cluster randomized clinical trial[END_REF][START_REF] Hsieh | The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment[END_REF][START_REF] Htut | Effects of physical, virtual reality-based, and brain exercise on physical, cognition, and preference in older persons: A randomized controlled trial[END_REF][START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF] reported significant improvement of cognitive functions. In future studies, it would be important to investigate the effect of cognitive or psychological components of the VR-PE such as cognitive challenges and gaming factors on improving cognitive function.

A previous meta-analytical review suggested that balance training using VR was an acceptable method for improving balance performance and functional mobility in community-dwelling older adults [START_REF] Donath | Effects of Virtual Reality Training (Exergaming) Compared to Alternative Exercise Training and Passive Control on Standing Balance and Functional Mobility in Healthy Community-Dwelling Seniors: A Meta-Analytical Review[END_REF]. In this SR, three studies were performed for community-dwelling older adults with and without mild cognitive decline [START_REF] Anderson-Hanley | 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[END_REF][START_REF] Bacha | Effects of Kinect Adventures Games Versus Conventional Physical Therapy on Postural Control in Elderly People: A Randomized Controlled Trial[END_REF][START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF]. Two studies of healthy older adults reported a significant improvement compared to the control group [START_REF] Park | A New Approach to Improve Cognition, Muscle Strength, and Postural Balance in Community-Dwelling Elderly with a 3-D Virtual Reality Kayak Program[END_REF] and pre-post change [START_REF] Bacha | Effects of Kinect Adventures Games Versus Conventional Physical Therapy on Postural Control in Elderly People: A Randomized Controlled Trial[END_REF] in general cognitive function. Moreover, one study performed for older adults with mild cognitive decline reported significant improvements in long-term memory and a self-report measure of cognitive function, and a pre-post difference in executive function [START_REF] Anderson-Hanley | 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[END_REF]. Although the number of included studies was small, this SR suggested the potential of the VR-PE to improve cognitive functions of community-dwelling older adults.

This study had some limitations. The first limitation was the small number of included studies. We found only six studies in healthy older adults and five studies in older adults with mild cognitive decline investigating VR effects on physical exercise. The second limitation is that previous studies used a wide variety of cognitive function measures, only a few studies used common cognitive function measures, such as the Stroop task. The third limitation was the small sample size of the included studies. Four of the eleven studies included fewer than 10 participants in each group [START_REF] Anderson-Hanley | 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[END_REF][START_REF] Delbroek | The effect of cognitive-motor dual task training with the biorescue force platform on cognition, balance and dual task performance in institutionalized older adults: A randomized controlled trial[END_REF][START_REF] Mrakic-Sposta | Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study[END_REF][START_REF] Monteiro-Junior | Virtual Reality-Based Physical Exercise With Exergames (PhysEx) Improves Mental and Physical Health of Institutionalized Older Adults[END_REF]. Due to these limitations, it is difficult to generalize the beneficial effects of VR-PE on each cognitive domain. However, as discussed above, the available evidence was enough to show that VR-PE has the potential to improve cognitive function in older adults.

Conclusions

We first conducted the SR for RCTs to investigate the benefits of VR-PE on cognitive function in older adults with and without mild cognitive decline. From 11 RCT studies (six studies for healthy older adults and five studies for older adults with mild cognitive decline), six studies reported significant improvements in several cognitive functions (general cognitive function, executive functions, working memory capacity, short-term memory, and verbal episodic memory) compared to the control group. The SR revealed that VR-PE could have beneficial effects on inhibition in older adults with and without mild cognitive decline. Moreover, VR-PE selectively leads to improvements in shifting and general cognitive performance in healthy older adults. The SR indicates that VR-PE would have a possibility to improve cognitive function in older adults. However, due to a small number of included studies, further studies will be necessary to draw a conclusion of the benefits of VR-PE on cognition. In addition, it would be important to investigate whether the VR-PE would have a positive effect on cognition in the young population as well as an aging population.

Figure 1 .

 1 Figure 1. PRISMA flowchart.

Figure 1 .

 1 Figure 1. PRISMA flowchart.

  Note. VE: VR-based exercise group; EC: exercise only control group; CC: cognitive only control group; ECC: exercise and cognitive control group; NC: no treatment control group; SD: standard deviation; Q1: first quartile; Q3: third quartile; MMSE: mini-mental state examination; MoCA: Montreal cognitive assessment; *: statistically significant improvement compared to the control group; †: statistically significant improvement from the baseline; n.s.: not significant.

	Healthcare 2021, 9, x FOR PEER REVIEW			4 of 15
	2016;	VE: 36	VE: 73.0 ± 3.0	VE: 22.6 ± 4.9
	Korea *	EC: 36	EC: 74.1 ± 2.9	EC: 22.9 ± 4.2

Table 1 .

 1 Characteristics of participants in the included studies.

Lead Author; Year; Country Sample Size (Female (%)) Age Cognitive Status

	Hsieh;	60 (72%)	(mean ± SD)
	2018;	VE: 31	VE: 76.4 ± 7.6	MMSE score 11-26
	Taiwan *	NC: 29	NC: 80.0 ± 7.5
	Eggenberger; 2015; Switzerland †	71 (65%) VE1: 24 VE2: 22 EC: 25	(mean ± SD) VE1: 77.3 ± 6.3 VE2: 78.5 ± 5.1 EC: 80.8 ± 4.7	MMSE (mean ± SD) VE1: 28.4 ± 1.4 VE2: 28.3 ± 1.2 EC: 28.0 ± 1.7
	Anderson-Hanley;	14 (50%)	(mean ± SD)	MoCA (mean ± SD)
	2018;	VE: 7	VE: 75.4 ± 9.83	VE: 22.0 ± 3.21
	United States *	EC: 7	EC: 80.9 ± 12.3	EC: 21.6 ± 2.70
	Mrakic-Sposta; 2018; Italy (n.s.)	10 (60%) VE: 5 NC: 5	(mean ± SD) VE: 72.0 ± 5.15 NC: 74.6 ± 6.43	MMSE (mean ± SD) 23.0 ± 3.4
				Performance ≤ -1.5 SD of
	Anderson-Hanley;	79 (78%)	(mean ± SD)	norm on at least one subtest
	2012;			(n)
	United States *	VE: 38	VE: 75.7 ± 9.9	VE: 16
		EC: 41	EC: 81.6 ± 6.2	EC: 14
	Bacha;	46 (74%)	(Medium [Q1; Q3])	MoCA (mean ± SD)
	2018;	VE: 23	VE: 71.0 (66.0; 74.5)	VE: 23.48 ± 4.94
	Brazil †	EC: 23	EC: 66.5 (65.0; 71.8)	EC: 22.52 ± 3.47
		84 (44%)	(mean ± SD)	MMSE (mean ± SD)
	Htut;	VE: 21	VE: 75.8 ± 4.89	VE: 25.5 ± 1.22
	2018;	EC: 21	EC: 75.9 ± 5.65	EC: 24.7 ± 0.96
	Thailand *	CC: 21	CC: 75.6 ± 5.33	CC: 25.2 ± 1.41
		NC: 21	NC: 76.0 ± 5.22	NC: 25.2 ± 1.00
	Delbroek;	20 (65%)	(mean ± SD)	MoCA (mean ± SD)
	2017;	VE: 10 (dropout: 2)	VE: 86.9 ± 5.6	VE: 17.7 ± 5.3
	Belgium (n.s.)	NC: 10 (dropout: 1)	NC: 87.5 ± 6.6	NC: 16.8 ± 5.8
	Liao;	34 (68%)	(mean ± SD)	MMSE (mean ± SD)
	2020;	VE: 18	VE: 75.5 ± 5.2	VE: 27.2 ± 1.9
	Taiwan †	ECC: 16	ECC: 73.1 ± 6.8	ECC: 28.3 ± 1.2
	Monteiro-Junior;	18 (67%)	(mean ± SD)	MMSE (mean ± SD)
	2017;	VE: 9	VE: 85.0 ± 8.0	VE: 21.0 ± 5.0
	Brazil *	EC: 9	EC: 86.0 ± 5.0	EC: 24.0 ± 4.0
	Park;	72 (94%)	(mean ± SD)	MoCA (mean ± SD)
	2016;	VE: 36	VE: 73.0 ± 3.0	VE: 22.6 ± 4.9
	Korea *	EC: 36	EC: 74.1 ± 2.9	EC: 22.9 ± 4.2

Note. VE: VR-based exercise group; EC: exercise only control group; CC: cognitive only control group; ECC: exercise and cognitive control group; NC: no treatment control group; SD: standard deviation; Q1: first quartile; Q3: third quartile; MMSE: mini-mental state examination; MoCA: Montreal cognitive assessment; *: statistically significant improvement compared to the control group; †: statistically significant improvement from the baseline; n.s.: not significant.

Table 2 .

 2 Quality assessment scores of included studies using modified Delphi list.

	Lead Author; Year; Country	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8	Q9 Q10 Q11 Q12 Q13 Q14	Total Score (Max. = 14)
	Hsieh; 2018; Taiwan	N	?	Y	Y	N	N	N	Y	Y	N	N	Y	Y	N	6
	Eggenberger; 2015; Switzerland	Y	Y	Y	Y	N	N	Y	N	N	Y	Y	Y	Y	Y	10
	Anderson-Hanley; 2018; United States	Y	?	Y	Y	?	?	?	Y	N	N	Y	Y	Y	Y	8
	Mrakic-Sposta; 2018; Italy	Y	?	Y	Y	?	?	?	Y	N	N	N	Y	Y	N	6
	Anderson-Hanley; 2012; United States	Y	Y	Y	Y	Y	?	?	Y	Y	Y	Y	Y	Y	Y	12
	Bacha; 2018; Brazil	Y	Y	Y	Y	Y	?	N	Y	N	Y	Y	Y	Y	Y	11
	Htut; 2018; Thailand	Y	?	Y	Y	Y	?	N	N	N	N	Y	Y	Y	N	7
	Delbroek; 2017; Belgium	Y	?	Y	Y	Y

Table 3 .

 3 Characteristics of intervention methods in the included studies.

	Lead Author; Year; Country	Periods of Intervention	VR Device	Experimental Group	Control Group
				VE: VR-based
	Hsieh; 2018; Taiwan *	Two 60 min sessions/week for 6 months	Xbox 360 Kinect, 100-inch flat screen	Tai Chi exercise exercise with (Chinese mind-body	NC: No intervention
				biofeedback)
				VE1: Video game
	Eggenberger; 2015; Switzerland †	Two 60 min sessions/week for 6 months	Impact Dance Platform, large screen	dancing on the pressure sensitive areas to detect steps VE2: Treadmill walking with verbal	EC: Treadmill walking without an additional cognitive task
				memory exercise
	Anderson-Hanley; 2018; United States *	≥Two ≥20 min sessions/week for 6 months	Cybercycle, virtual reality display (small monitor)	VE: VR-bike rides with effortful cognitive videogame	EC: VR-bike rides with passive cognitive processing
	Mrakic-Sposta;	Three 40-45 min	Cycle-ergometer,	VE: Cycling exercise
	2018;	sessions/week	finger touch	with VR-based	NC: No treatment
	Italy (n.s.)	for 6 weeks	projector	cognitive training
	Anderson-Hanley; 2012; United States *	Five 45 min sessions/week for 3 months	Cybercycle, virtual reality (small monitor) display	VE: VR-bike rides with virtual 3D tours	EC: Traditional stationary bike rides
	Bacha;	Two 60 min	Xbox Kinect	VE: Playing Kinect	EC: Conventional
	2018;	sessions/week	Adventures,	games including	physical therapy
	Brazil †	for 7 weeks	50-inch TV	cognitive demands	exercises
					EC: Strength and
	Htut; 2018; Thailand *	Three 30 min sessions/week for 8 weeks	Xbox 360	VE: VR-based exercise games	balance exercises CC: Brain exercise games
					NC: no exercise
	Delbroek; 2017; Belgium (n.s.)	Two 18-30 min sessions/week for 6 weeks	BioRescue, 55-inch TV-flat screen	VE: VR cognitive-motor dual task training	NC: No intervention (usual care)
	Liao; 2020; Taiwan †	Three 60 min sessions/week for 12 weeks	Microsoft Kinect, VIVE system	VE: VR-based physical and cognitive training	ECC: Combined physical and cognitive training
	Monteiro-Junior; 2017; Brazil *	Two 30-45 min sessions/week for 6-8 weeks	Wii Fit Plus	VE: Playing VR-based exercise games	EC: Playing exercise games
	Park; 2016; Korea *	Two 30+20 min sessions/week for 6 weeks	Kayak ergometers 3-D beam projector	VE: Conventional exercise & VR kayak paddling exercise	EC: Conventional exercise
	Note. VE: VR-based exercise group; EC: Exercise only control group; CC: Cognitive only control group; ECC: Exercise and cognitive control
	group; NC: No treatment control group; *: Statistically significant improvement compared to the control group; †: Statistically significant
	improvement from the baseline; n.s.: Not significant.

Table 4 .

 4 Description of Measured Cognitive Function.

	Lead
	Author;
	Year; Country

Table 4 .

 4 Cont.

	Liao;
	2020;	MoCA †	EXIT-25 †
	Taiwan †

*: Statistically significant improvement compared to the control group; †: Statistically significant improvement from the baseline; n.s.: Not significant; MMSE: Mini-mental state examination; MoCA: Montreal cognitive assessment; ABSTR: Abstract thinking and judgment; CASI: Cognitive abilities screening instrument; ANML: Animal name fluency; ATTEN: Attention; MENMA: Mental manipulation; TMT-B: Trail making test part B; WMS-R: Wechsler memory scale-revised; TMT-A: Trail making test Part A; DSST: Digit symbol substitution task; WAIS-R: Wechsler adult intelligence scale-revised; ADAS: Alzheimer's disease assessment scale; FAB: Frontal assessment battery; VF: Verbal fluency test; RAVLT_I: Immediate recall of Rey auditory verbal learning test; RAVLT_D: Delayed recall of Rey auditory verbal learning test; AM: Attentional matrices test; ROCFT: Rey-Osterrieth complex figure test; FAQ: Functional activity questionnaire; COWAT: Controlled oral word association test; LDST: Letter digit symbol test; TUG-cog: Timed up and go test cognition; TUG-DT: Timed up and go test dual attention task; EXIT-25: Executive interview 25; CVVLT: Chinese version of the California verbal learning test; FMT: Floor maze test; ANOVA: Analysis of variance; ANCOVA: Analysis of covariance.

This study was supported by a grant from the Tohoku University-Université de Lorraine Joint Research Fund 2020. We were also supported by JSPS KAKENHI Grant Numbers 16KT0002 and 19H01760 (Grant-in-Aid for Scientific Research (B) and 19H05003 (Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)). None of the funding sources had any involvement in the study design, collection, analysis, interpretation of data, or writing of the paper.

Institutional Review Board Statement: Not applicable.

Data Availability Statement: Not applicable.

Conflicts of Interest:

The authors declare no conflict of interest.