Age-associated motor and cognitive deficits increase the risk of falls, a major cause of morbidity and mortality. Emerging evidence suggests that inflammatory mediators lead to impaired functional capacity and frailty in the elderly and suggests that immune system mediated inflammation in the brain play an important role in cognitive decline. Substantial literature has also demonstrated that age-targeted physical activity training are promising strategies for promoting the motor-cognitive process across the adult lifespan. Recently, the virtual reality (VR) application has been implemented in the neuropsychological rehabilitation settings suggesting that the VR-infused daily living activities may benefit the transfer of intervention outcomes and to promote autonomy in function of daily living such as cooking or grocery shopping. However, it remains unclear the effect of the VR-based exercise intervention (motor-cognitive impact) on older adults' cognitive function and fall prevention. The literature suggests that the similarity of VR exercises with real life activities may improve generalizability by extending the transfer of gains of training to everyday living and promote some aspects of quality of life in older adults. It is also unclear to what extent these aging-associated motor- cognitive changes may be affected by VR rehab games and whether systemic- and neuro-inflammation is ameliorated by this novel intervention in older adults.

This purpose of this study is to design and implement a Virtual Reality-Infused Treadmill Training on Aging-Related Outcomes (V-TARGET) intervention, focusing on adults (aged up to 75 years old). The study will compare the effects of V-TARGET intervention (self-paced treadmill-simulator exercise with VR rehab games) against a control group on motor-cognitive function, health-related quality of life (HRQOL), circulating inflammatory markers and cerebral/peripheral blood flow through this 5-week intervention (2 times/week, 30-minutes/session, 10 sessions total).

A randomized controlled trial using a repeated measure design with a 1-month follow-up assessment will be employed. The study will compare the effects of V-TARGET intervention (self-paced treadmill exercise augmented by VR rehab games) against an active-control paradigm (self-paced treadmill exercise without VR rehab games) on motor-cognitive function, health-related quality of life (HRQOL), and circulating inflammatory markers through a 5-week V-TARGET intervention (2 times/week, 30-minutes/session, total 10 sessions). Specifically,

Primary Aim 1: To examine the effects of a 5-week V-TARGET intervention on motor function (i.e., balance/mobility and rate of fall), cognitive function (i.e., working memory and executive function), and HRQOL among older adults.

It is hypothesized that after controlling for socio-demographic variables (i.e., age, gender, SES, body mass index [BMI]), and physical activity history, individuals in the V-TARGET group would exhibit more improvement in the motor and cognitive function and better HRQOL after the intervention compared to individuals in the active control group. It is hypothesized that gains made by the experimental group at post-treatment would be maintained or enhanced at the 1-month follow-up.

Secondary Aim 2: To determine whether a 5-week V-TARGET intervention alters circulating inflammatory markers in older adults. Circulating levels of interferon (IFN)-γ, CXCL10, T cell IFN-γ production and cell surface expression of CXCR3 (the receptor for CXCL10) will be measured .

It is hypothesized that V-TARGET intervention will result in downregulation of the T cell/IFN-γ/CXCL10 inflammatory cascade and that these changes represent a potential biological mechanism by which the V-TARGET intervention improves motor-cognitive function in older adults with high risk of fall. It is hypothesized that gains made by the experimental group at post-treatment would be maintained or enhanced at the 1-month follow-up.

Secondary Aim 3: To examine the effects of a 5-week V-TARGET intervention on Cerebrovascular Health among older adults.

It is hypothesized that after controlling for socio-demographic variables (i.e., age, gender, SES, body mass index [BMI]), and physical activity history, individuals in the V-TARGET group would exhibit more improvement in the Cerebrovascular Health after the intervention compared to individuals in the active control group. It is hypothesized that gains made by the experimental group at post-treatment would be maintained or enhanced at the 1-month follow-up.

Inclusion Criteria:

1. adults aged up to 75 years old
2. able to walk independently, without use of an assistive device
3. English speaking

Exclusion Criteria:

1. self-disclosed limited mobility in joint(s) due to arthritis or other condition that would prevent participation
2. any ongoing orthopedic injury
3. cardiac surgery or any ongoing cardiovascular issues preventing participation or physical activity.
4. motor/cognitive disorders (Alzheimer's disease, Parkinson's disease, dementia, etc.)
5. use of a wheelchair

This study is open to participants of all genders, including individuals who self-identify as male, female, non-binary, genderqueer, or any other gender identity. Individuals who self-identify as transgender or cisgender are welcomes. If participants' gender identity does not fit within traditional male or female categories, participation of the study is still welcomed.

Individual participant data (IPD) may not be shared due to concerns related to participant privacy and confidentiality. While efforts are made to de-identify all data, the sensitive nature of the information collected in this study could potentially lead to the identification of participants if shared publicly. Additionally, current consent forms do not explicitly allow for the sharing of individual data outside of the research team.

If future updates to consent or data protection protocols allow for IPD sharing, and with appropriate safeguards in place, it may be reconsidered to share IPD under controlled access conditions. For now, only aggregated data and study results will be shared to maintain the privacy of our participants.