Table 1.

Summary of the included studies.

Study	Sample	Multimorbidity, chronicity, and frailty assessment	Primary outcomes	CMDTa technology	Type of intervention	Session details	Main results
Mirelman et al [51], 2011	20 PDb	Disease duration	Usual gait Gait during DTc Gait during endurance testing Obstacle negotiation TMT-ABd UPDRSe motor scores, FSSTf, PDQ-39g	Semi-immersive VRh motion system (V-TIMEi project)	Open-label trial CMDT group: walking on a treadmill while negotiating virtual obstacles presented on a screen in front of the treadmill. TAUj group: historical active control group (physical treadmill training)	6 weeks: 18 sessions, 3 times a week for 45 minutes follow-up: 4 weeks	Similar results were obtained for the CMDT and TAU groups for DT gait parameters (eg, gait speed, stride length). However, gains were greater for the experimental group. Gait speed during usual walking, endurance, gait speed while obstacles negotiation increased after CMDT, and they were maintained over follow-up. DT gait speed and DT gait variability improved after training and at follow-up. Major improvements were found also in TMT-AB, UPDRS motor scores, FSST, and PDQ-39.
Mirelman et al [20], 2016	282 patients: 130 PD, 43 MCIk, 109 with IFl	PD duration, number of prescribed medications, history of falls	Incident rate of falls in the 6 months after the end of the training	Semi-immersive VR motion system (V-TIME project)	RCTm CMDT group: walking on a treadmill while negotiating virtual obstacles presented on a screen in front of the treadmill. TAU group: walking on a treadmill	6 weeks: 18 sessions, 3 times a week for 45 minutes Follow-up: 6 months	CMDT outperforms TAU condition in reducing fall incident rate, especially in PD. Obstacle clearance was improved in the CMDT compared with TAU. Endurance, obstacle clearance, mobility, and quality of life were maintained at follow-up in the CMDT group. Gait speed during usual and obstacle negotiation gait, cognitive functions, and physical performance improved in both groups.
Delbroek et al [52], 2017	20 MCI	Not reported	MoCAn POMAo and iTUGp iTUG during DT	VR exergame (BioRescue)	RCT CMDT group: 9 exercises, including obstacle negotiation, weight-bearing transfer exercises, and cognitive operation with weight-bearing exercises. TAU group: low-intensity strength and flexibility exercises for the upper body while seated.	6 weeks: 12 sessions 2 times a week. The duration gradually increased from 18 minutes (week 1) to 30 minutes (week 5) No follow-up	iTUG parameters improved for the CMDT compared with TAU. No changes in the POMA, iTUG, and MoCA scores in both groups were observed.
Wiloth et al [13], 2017	99 cognitive impairment (probable dementia)	Number of medications and diagnoses, history of falls, living situation	Physiomat performance (trained and untrained)	VR exergame (Physiomat)	RCT CMDT group: by shifting weight while holding onto the handles of the Physiomat, participants had to complete 2 cognitive tasks FTBTq: moving a yellow ball on the screen as fast as possible from the center of the screen to the target items PTMTsr: connect numbers provided as fast as possible on 5 different levels. TAU group: nonspecific, low-intensity training on strength and flexibility for the upper body while seated.	10 weeks: 20 sessions, 2 times a week for 90 minutes Follow-up: 3 months	Trained and untrained FTBT and PTMTs parameters (eg, accuracy, time) improved after CMDT compared with TAU group. Effects were maintained at follow-up for trained tasks.
Maidan et al [53], 2018	64 PD	Disease duration	Prefrontal HbO2s with f-NIRSt and gait were assessed during 3 walking tasks: usual walking, walking while serially subtracting 3 seconds from a given 3-digit number (DT), and walking while negotiating obstacles Incident rate of falls in the 6 months after the end of the training Neuropsychological test battery	Semi-immersive VR motion system (V-TIME project)	RCT CMDT group: walking on a treadmill while negotiating virtual obstacles presented on a screen in front of the treadmill. TAU group: walking on a treadmill.	6 weeks: 18 sessions, 3 times a week for 45 minutes Follow-up: 6 months	CMDT reduced prefrontal activation during usual walking and complex walking conditions compared with TAU. EFu and falls incident rate at 6 months improved in the CMDT group. Both interventions improved gait parameters (eg, speed, stride length).
Werner et al [54], 2018	99 cognitive impairment (probable dementia)	Number of medications and diagnoses, history of falls, living situation	Physiomat performance (FTBT, PTMTs)	VR exergame (Physiomat)	Secondary analyses of an RCT CMDT group: see Wiloth et al [13], 2017. ERsv: participants with an individual decrease in the duration after TS7w that exceeded the RCIx either for the most complex Physiomat task completed at T1y or for at least 50% of the Physiomat tasks completed at T1. NERsz: all other participants. TAU group: low-intensity strength and flexibility exercises for the upper body while seated.	10 weeks: 20 sessions, 2 times a week for 90 minutes No follow-up	From T1 to TS7: substantial improvements in the FTBT and PTMT level 1, 2, and 3-5. From TS7 to TS14: substantial improvements in the PTMT level 2 and 4. From TS14 to T2: substantial improvements in the PTMT level 1 and 4. From TS7 to T2: substantial improvements in the FTBT and PTMT level 1 and 3-5. ERs had lower visuospatial ability, DT performance, and Physiomat compared with NERs. The predictors of an early CMDT response are visuospatial ability, DT performance, and Physiomat
Pelosin et al [55], 2018	96 PD	Disease duration, history of falls	Gait under dual-task condition EF Incident rate of falls in the 6 months after the end of the training	Semi-immersive VR motion system (V-TIME project)	RCT 6 versus 12 weeks of CMDT training aided with technology CMDT group: walking on a treadmill while avoiding virtual obstacles projected on the screen.	6 weeks: 18 sessions, 3 times a week for 45 minutes Follow-up: 1 and 6 months 12 weeks: 32 sessions, 3 times a week for 45 minutes Follow-up: 1 and 6 months	Both interventions improved, and maintained over follow-up, gait parameters during DT, obstacle negotiation, or usual gait. EF improved at posttest and 1-week follow-up for the 12-week CMDT. Incident rate of falls improved in both groups, but results were stronger for the 12-week interventions. Fear of falling improved and was maintained in the 12-week program
Spanò et al [34], 2022	26 CVDaa with history of falls	No detailed information reported	Balance and gait (also DT) Fear of falling Physical performance and gait speed	Semi-immersive virtual room with a motion-tracking system	RCT pilot study CMDT group: simultaneous administration of motor and cognitive tasks, with sensory carpets and with walkable LED floor. TAU group: individual underwent combined motor and cognitive training.	DT: 5 weeks: 15 sessions, 3 times a week for 40 minutes No follow-up TAU: 5 weeks: 15 sessions, 3 times a week for 60 minutes total	CMDT improved gait and balance (POMA) and fear of falling but not gait endurance. TAU did not show any improvements. Gait under DT was improved in the CMDT group only. No other effects were found.

^aCMDT: cognitive-motor dual-task.

^bPD: Parkinson disease.

^cDT: dual-task.

^dTMT-AB: Trail Making Test A/B.

^eUPDRS: Unified Parkinson’s Disease Rating Scale.

^fFSST: four square step test.

^gPDQ-39: Parkinson’s Disease Questionnaire.

^hVR: virtual reality.

ⁱV-TIME: Virtual Reality-Treadmill Combined Intervention for Enhancing Mobility and Reducing Falls in the Elderly.

^jTAU: treatment as usual.

^kMCI: mild cognitive impairment.

^lIF: idiopathic falls.

^mRCT: randomized control trial.

ⁿMoCA: Montreal Cognitive Assessment.

^oPOMA: performance-oriented mobility assessment.

^piTUG: instrumented Timed Up and Go.

^qFTBT: follow the ball task.

^rPTMT: trail making task.

^sHbO₂: oxyhemoglobin.

^tf-NIRS: functional near-infrared spectroscopy.

^uEF: executive function.

^vER: early responders.

^wTS: training session.

^xRCI: reliable change index.

^yT1: baseline.

^zNER: nonearly responder.

^aaCVD: cerebrovascular disease.