Motor-Cognitive Training for Motoric Cognitive Risk Syndrome

The objective of this single-blind randomized controlled trial is to compare the effects of combined motor-cognitive training using a virtual reality treadmill with motor training using a conventional treadmill in older adults with Motoric Cognitive Risk (MCR) syndrome. MCR is a geriatric condition characterized by slow gait speed and subjective cognitive complaints. The coexistence of motor and cognitive impairments in individuals with MCR significantly increases their risk of developing dementia. To date, randomized controlled trials investigating active interventions that simultaneously target both motor and cognitive functions remain scarce. This study will examine whether 18 training sessions, delivered over six weeks at a frequency of three 1-hour sessions per week, using a virtual reality treadmill lead to greater improvements in motor and cognitive outcomes compared to conventional treadmill training.

• Virtual Reality Treadmill Training (Behavioral): The Virtual Reality Treadmill Training (VRTT) group will complete 18 training sessions over six weeks (three 1-hour sessions per week). Participants will perform prescribed tasks designed to challenge motor, cognitive, and motor-cognitive functions within a VR environment projected onto a screen in front of the treadmill (Fig 1). The VRTT system includes a conventional treadmill with a harness suspension system, camera-based motion capture (Intel RealSense, Santa Clara, CA), and a computer-generated simulation (GaitBetter, Tel Aviv, Israel). The camera tracks the participant's feet movements, which are displayed within the VR environment, allowing participants to see their feet navigating obstacles, pathways, and narrow corridors. Each session will include three walking bouts interspersed with rest breaks, targeting at least 40 minutes of active motor-cognitive training.
• Treadmill Training (Behavioral): Participants in the Treadmill Training (TT) intervention will follow a traditional TT program without feedback from the VR system. 70 The focus will be on increasing gait speed and distance, with no motor-cognitive training such as obstacle crossing or cognitive tasks while walking.

Primary outcomes

• Dual-task gait speed [From enrollment to the end of treatment at 6 weeks]: 6 minute walk test on a 25-meter walkway while completing auditory oddball task
• Cognition [From enrollment to the end of treatment at 6 weeks]: Uniform Data Set (UDS) 4.0 global cognition composite score
• Gait speed [From enrollment to the end of treatment at 6 weeks]: Gait speed on 4-meter walk test (4MWT)
• Cognitive complaints [From enrollment to the end of treatment at 6 weeks]: Self-report of cognitive complaints based on memory item of the Geriatric Depression Scale (GDS): yes - no

Secondary outcomes

• Dual task cost [From enrollment to the end of treatment at 6 weeks]: Motor and cognitive dual task cost defined using ((dual task - single task) / single task) * 100
• Spatiotemporal gait characteristics [From enrollment to the end of treatment at 6 weeks]: Inertial Motion Units will collect spatiotemporal gait characteristics during single-task and dual-task walking
• Cognitive domain scores [From enrollment to the end of treatment at 6 weeks]: Uniform Data Set 4.0 (UDS) cognitive domain scores
• P3 event-related potential (ERP) [From enrollment to the end of treatment at 6 weeks]: P3 event-related potential (ERP) extracted from electroencephalography during oddball test
• Mitochondrial function [From enrollment to the end of treatment at 6 weeks]: Mitochondrial functional index collected from blood serum

Other outcomes

• Real-world physical activity and gait data [From enrollment to the end of treatment at 6 weeks]: Physical activity and gait data collected from activity sensors
• Depression [From enrollment to the end of treatment at 6 weeks]: Scores on the Geriatric Depression Scale (GDS): range 0 - 15; higher score is worse
• Health-related Quality of life [From enrollment to the end of treatment at 6 weeks]: Scores on Short Form 36 (SF-36): range 0 - 100; higher score is better
• Frailty [From enrollment to the end of treatment at 6 weeks]: Scores on the Evaluative Frailty Index for Physical Activity (EFIPA): range 0 - 1; higher score is worse
• Falls [From enrollment to the end of treatment at 6 weeks]: Self-report of falls via falls diaries
• Resilience [From enrollment to the end of treatment at 6 weeks]: Brief Resilience Scale (BRS): range 6 - 30; higher scores are better

Sex: All, ages: 65 Years to any

Inclusion Criteria:

* Age ≥ 65
* English speaking
* Normal cognition (CDR=0)
* Meet MCR criteria
* Voluntary consent

Exclusion Criteria:

* Major chronic unstable disease or neurological condition (e.g., seizures)
* Diagnosed dementia
* Active psychiatric conditions
* Musculoskeletal conditions that affect walking for more than 2 minutes
* Severe visual or hearing impairments
* Sedating drugs (new use of narcotics or anxiolytics within the past month or chronic use that causes sedation)
* Currently engaged in other non-pharmacological interventions to improve cognition or walking