Enhancing Physical Reserve to Promote Resilience in Physically Frail Older Adults (MRI exercise)

Enhancing Physical Reserve to Promote Cognitive and Physical Resilience in Physically Frail Older Adults: A 3-Month Randomized Controlled Trial

The goal of this clinical trial is to assess the efficacy of combined aerobic and resistance training in enhancing physical reserve in older adults with physical frailty. Investigator contend that enhanced physical reserve will enable preservation of cognitive and physical function. The main questions aims to answer are: (1) Compared with usual care (i.e., CON), will 3-month aerobic and resistance training (ATRT) improve physical reserve in older adults with physical frailty? (2) Compared with CON, will ATRT lead to changes in the neural network organization? (3) Will improved physical reserve lead to better maintenance of cognitive and physical functioning in spite of presence of white matter hyperintensities (WMH)?

Study Overview

• Status: Recruiting
• Conditions: Frailty at Older Adults
• Intervention / Treatment: Behavioral: Aerobic and resistance training; Behavioral: Usual Care

Detailed Description

Objectives: (1) To compared with usual care (i.e., CON), will 3-month aerobic and resistance training (ATRT) improve physical reserve in older adults with physical frailty? (2) Compared with CON, will ATRT lead to changes in the neural network organization? (3) Will improved physical reserve lead to better maintenance of cognitive and physical functioning in spite of presence of white matter hyperintensities (WMH)? (4) What is the association between exercise, neural network, and physical reserve? Hypotheses: Investigator hypothesize that (1) compared to participants randomly assigned to the CON, participants randomly assigned to the 3-month ATRT will show significantly enhanced physical reserve. (2) compared with participants randomly assigned to CON, participants randomly assigned to ATRT will show reduction in Dorsal Attention Network connectivity. (3) Enhanced physical reserve will moderate the negative association between WMH and Trail Making Test performance, as well as WMH and Short Physical Performance Battery performance. (4) combined aerobic and resistance training will enhance physical reserve via a mediated relationship with reduced Dorsal Attention Network connectivity.

Design and subjects: A randomized controlled trial involving 224 community-dwelling older adults with physical frailty Study instruments: Magnetic resonance imaging Interventions: The designed exercise training will be progressive and moderate in intensity. Participants randomized to the ATRT group will undergo a 3-month (i.e., 13-weeks) four-sessions-per-week, 60-minute-per-session exercise with a 10-minute warm-up, 40-minute of moderate intensity exercise training, and 10-minute cool-down. There will be a total of 52 exercise sessions with a 1:3 research staffs (i.e., instructor and assistants) to study participants ratio. To promote participant safety, investigator will limit each session to 12 study participants. To ensure fidelity of the intervention across time, a detailed manual of procedures for each experimental group will be developed and used for staff training.

Data analysis: All analyses will follow the intent to treat principle. The principle investigator will lead all analyses with support from collaborators on WMH quantification and structural MRI analyses. The intention-to-treat analysis will be conducted with multiple imputation followed by a complete-case analysis. Statistical significance for all analyses will be defined at α < 0.05.

• Study Type: Interventional
• Enrollment (Estimated): 224
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chun Liang HSU, PhD; Phone Number: 852-27666755; Email: chun-liang.hsu@polyu.edu.hk

Study Locations

• Hong Kong
  • Hong Kong
    • Hong Kong, Hong Kong, Hong Kong, 0000000
      • Recruiting
      • The Hong Kong Polytechnic University, Department of Rehabilitation Sciences
      • Contact: Chun Liang HSU, PhD; Phone Number: 27666755; Email: chun-liang.hsu@polyu.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. are community-dwelling (i.e., not residing in a nursing home or extended care unit) ;
2. scored < 9/12 on the SPPB;
3. scored >18/30 on the MoCA;
4. are able to walk independently; use of walking aid is acceptable;
5. are able to safely engage in exercise as indicated by the Physical Activity Readiness Questionnaire Plus33 and confirmed by their physician;
6. have internet at home; and
7. are able to provide written informed consent.

Exclusion Criteria:

1. diagnosed with dementia or stroke;
2. self-report engaging in strength and balance training exercises > two-times-per-week in the 3 months prior to screening;
3. unable to understand, speak, and read Cantonese/Chinese/English proficiently; and
4. contraindications for MRI such as MRI-incompatible implants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aerobic and resistance training; Participants will complete two aerobic training sessions and two resistance training sessions per week for a total of four exercise training sessions each week lasting for 3-month (i.e., 13-weeks). Aerobic exercise intensity will be tracked through heart-rate monitors with an age-specific targeted heart-rate-reserve initially set at 50% and progressively increased by 5% weekly until 70% heart-rate-reserve is reached in Week-5, then it will be sustained for the remainder of the trial. The first four weeks of the resistance training program will emphasize on assisting the study participants in gaining familiarity with proper technique. The intensity of the resistance training stimulus will be set to a weight where the participants can complete two sets of 10-15 repetitions, then progressed from 45% to 85% of predicted 1-repetition-maximum determined at Week-4 using the 8-rep maximum test. The 8-rep maximum test is rrepeated every 4 weeks to ensure the exercise intensity is maintained	Behavioral: Aerobic and resistance training; The aerobic training sessions will involve standardized sets of stationary training, including on-spot jogging, burpees, aerobic steppers, agility ladders, and non-contact boxing. Each participant will rotate through the stations within the 40-minute training period, with one-minute of rest breaks in-between each station. A 20-point rate-of-perceived exertion will be used to monitor participant status during training with a target rate-of-perceived exertion of 16-17. The resistance training sessions will involve utilizing free weights and resistance bands to stimulate muscle strength. The set of movements include triceps extension, dumbbell bicep curls, seated overhead dumbbell press, bent-over dumbbell row, wall squats, standing calf raises, wall push-ups.
Placebo Comparator: Usual care; Participant Retention and Care: Investigator will implement strategies to promote participant retention by: (1) conducting monthly phone calls by the project assistant to encourage and motivate participants to stay within the study; (2) discussing participant barriers/distress and developing coping/action plans; (3) providing monthly updates in the form of in-person/online/phone sessions; and (4) offering a comprehensive report on cognitive function, mobility, brain MRI, and monetary compensation for their time upon completion of the study. Investigator will facilitate participant care by recording incidental findings from the MRI and providing clinical assessment data that may be shared with healthcare providers upon request. All personnel on the research team will be trained to detect/assess distress or any possibility of harm and respond appropriately.	Behavioral: Usual Care; Participant Retention and Care: Investigator will implement strategies to promote participant retention by: (1) conducting monthly phone calls by the project assistant to encourage and motivate participants to stay within the study; (2) discussing participant barriers/distress and developing coping/action plans; (3) providing monthly updates in the form of in-person/online/phone sessions; and (4) offering a comprehensive report on cognitive function, mobility, brain MRI, and monetary compensation for their time upon completion of the study. Investigator will facilitate participant care by recording incidental findings from the MRI and providing clinical assessment data that may be shared with healthcare providers upon request. All personnel on the research team will be trained to detect/assess distress or any possibility of harm and respond appropriately.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30 seconds sit-to-stand test	Mobility	Baseline and 3 months
Quantification of physical reserve	Physical reserve will be operationally defined as the unexplained residual variance in 30-second Sit-to-Stand Test after accounting for the effects of age, cognitive capacity, and brain structural integrity.	Baseline and 3 months
Alzheimer's Disease Assessment Scale-Cognitive-13	Cognitive capacity will be assessed by the Alzheimer's Disease Assessment Scale-Cognitive-13. It measures memory, language, praxis, attention, and executive function, with scores ranging from 0 to 85; higher scores indicate greater cognitive impairment.	Baseline and 3 months
Total hippocampal volume	Total hippocampal volume will be selected to reflect brain structural integrity	Baseline and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trail Making Test	The Trail Making Test will comprise Part A and Part B. In Part A, participants are instructed to connect numbers in sequential order (e.g., drawing a line from 1 to 2, 2 to 3, 3 to 4, etc.) while being timed. In Part B, participants are instructed to connect, in order, 25 encircled numbers and letters alternately (e.g., 1-A-2-B-3-C) while being timed. A longer time represents worse executive function.	Baseline and 3 months
Resting state functional connectivity	Functional MRI will be used to measure resting state functional connectivity	Baseline and 3 months
Education	Years of education of participants will be recorded	Baseline and 3 months
Physical Activity Scale for the EAlderly	Physical activity will be assessed by the Physical Activity Scale for the Elderly. Higher scores represent better physical activity.	Baseline and 3 months
Body mass index	Body mass index will be calculated as weight in kilograms divided by height in meters squared (kg/m²).	Baseline and 3 months
Pictorial Fit-Frail Scale	Physical frailty will be assessed by the Pictorial Fit-Frail Scale. It involves 14 domains, with scores ranging from 0 to 43; higher scores indicate severely frail.	Baseline and 3 months
Short Physical Performance Battery	Physical frailty will be measured by the Short Physical Performance Battery. It measures balance, walking, and sit to stand, with scores ranging from 0 to 12; higher scores indicate greater mobility.	Baseline and 3 months
The Montreal Cognitive Assessment	General cognitive function will be assessed by the Montreal Cognitive Assessment. It measures memory, language, visuospatial, attention, and abstract reasoning, with scores ranging from 0 to 30; higher scores indicate greater general cognition.	Baseline and 3 months
Functional Comorbidity Index	Total number of comorbid conditions will be assessed through the Functional Comorbidity Index , with a maximum score of 18. A lower score indicates fewer comorbidities.	Baselin and 3 months
Sleep duration	Sleep duration will be recorded in hours over the last 24 hours and the last 7 days.	Baselin and 3 months

Collaborators and Investigators

• Sponsor: The Hong Kong Polytechnic University

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: March 23, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; aerobic exercise; resistance training; physical frailty; physical reserve
• Additional Relevant MeSH Terms: Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Physical Therapy Modalities; Patient Care; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Physical Conditioning, Human; Exercise; Resistance Training
• Other Study ID Numbers: HSEARS20250709003; 25603525 (Other Grant/Funding Number: Research Grants Council, Hong Kong SAR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Investigators will create a de-identified dataset to share at the time of publishing the primary results of our trial or within 9 months of database lock, whichever comes first. The data to be shared include but not limited to: de-identified instrument item and total scores of primary and secondary outcomes; de-identified exercise session report data
• IPD Sharing Time Frame: Dec 2028
• IPD Sharing Access Criteria: a commitment to using the data only for research purposes and not to identify an individual participant; a commitment to securing the data using appropriate computer technology; a commitment to destroying or returning the data after analyses are completed; all data sharing requests must be reviewed and approved by the PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No