Optimising Exercise to Improve Physical and Cognitive Frailty in Mild Cognitive Impairment

This investigational research aims to understand the mechanism of delaying the progression of dementia through different types of exercise. Exercise plays a protective role by attenuating the progression of cognitive impairments in mild cognitive impairment (MCI), an early and reversible stage of dementia. However, how different types of exercise induce changes in physical frailty and cognitive function is understudied. The participants will be randomized to receive an exercise intervention program (cycling or strength training) for 12 weeks or a control group.

The participants will be asked to perform certain cognitive and physical assessments at the start of the study, at the end of 12 weeks of exercise intervention, and 4 weeks after the end of the intervention. Below is the list of the assessments:

• Patient Health Questionnaire-9 (PHQ-9)
• World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0-12)
• Self-report on sociodemographic characteristics, ethnicity, socioeconomic status, educational level, smoking status, alcohol intake, comorbidities, chronic medications, social activities, history of falls
• body height, weight and fat percentage, heart rate, blood pressure, Dual-Energy X-Ray Absorptiometry (DEXA) scan: measurements to evaluate overall physical characteristics
• handgrip strength: to evaluate musculoskeletal function
• Stroop test: to evaluate information processing speed and executive cognitive control
• n-back task: to evaluate working memory and executive function
• Timed Up and Go (TUG) test: to measure balance
• single-task gait: to measure walking ability
• double-task gait: to measure walking stability and attention

During Stroop test, n-back task, Timed Up and Go (TUG) test, single-task gait and double-task gait, the participants will be equipped with a mobile functional near-infrared spectroscopy (fNIRS) device over their forehead. This device is used to detect changes in blood flow in the front area of the brain.

Their participation will last approximately 18 weeks (2 weeks of familiarization and assessment, 12 weeks of exercise intervention, and 4 weeks of follow-up).

Study Overview

• Status: Not yet recruiting
• Conditions: Mild Cognitive Impairment (MCI)
• Intervention / Treatment: Other: Exercise training

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 637616
    • National Institute of Education
    • Contact: Wei-Peng Assoc Prof Teo, PhD; Phone Number: (+65) 6790-3704; Email: weipeng.teo@nie.edu.sg
    • Sub-Investigator: Shazlin Shaharudin, PhD
    • Sub-Investigator: Angela Frances Hui Wen Yap, PhD, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

1. males and females aged 60 until 85
2. living in the community,
3. confirmed diagnosis of MCI
4. able to walk without assistance for at least two minutes,
5. able to participate in exercise intervention screened by a physician based on ACSM guidelines

Exclusion criteria:

1. uncertain diagnosis of MCI,
2. did not screen for ability to participate in exercise intervention,
3. presence of other neurological, psychiatric, or cognitive impairment disorders,
4. seriously ill, presence of Hepatitis B or C, cancer, and patients on immunosuppressant drugs,
5. type 2 diabetes mellitus,
6. uncontrolled hypertension or hypotension (systolic blood pressure >160 mm Hg and/or diastolic blood pressure >100 mm Hg at rest),
7. unstable cardiac, renal, lung, liver, or other severe chronic disease,
8. history of myocardial infarction and/or stroke within previous year,
9. vision/hearing disorder,
10. musculoskeletal disorders that affect physical function such as osteoporosis, severe knee osteoarthritis, and degenerative spinal condition,
11. presence of any major psychiatric disorder (a clinical diagnosis of major depressive disorder, bipolar or schizophrenia)
12. history of vitamin B12 deficiency or hypothyroidism (stable treatment for at least 3 months is allowed)
13. serious or non-healing wound, ulcer, or bone fracture

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Resistance exercise; There are 4 lower limb exercises namely seated knee extension, plantar flexion through calf raises, hip abduction by moving the straight leg sideways, and hip extension by moving the straight leg backwards. The three standing exercises will be conducted while the participants hold on to a chair. Exercise intensity will be increased gradually by increasing the number of repetitions and by affixing weights around the ankles. All participants will start with 3 sets of 8 repetitions for each leg without weights. When a participant performs an exercise with ease, the number of repetitions will be increased to 10 in the next session, and 12 in the session thereafter. When a participant can correctly perform 12 repetitions without weights, at RPE <12, a weight of 0.5 kg will be attached to their ankles. Each exercise session will end with 5-min stretching. HR will be monitored and recorded continuously during exercise session.	Other: Exercise training; Participation will last approximately 18 weeks (2 weeks of familiarization and assessment, 12 weeks of exercise intervention, and 4 weeks of follow-up). Participants will be randomized into three groups, either cycling group, strength training group or control group. Those in the cycling group and strength training group will undergo exercise intervention for about 2 sessions per week for 12 weeks (total 24 times) and will be followed for 4 weeks. The study will involve 28 visits. All groups will continue usual care at Singapore General Hospital. The control group will have usual care only during the duration of this study.
Experimental: Aerobic exercise; The aerobic group will perform moderate intensity walking sessions indoors. The targeted exercise intensity corresponds to 50-60% of the individual heart rate reserve (HRR, HRmax-HRresting) during the first two weeks and 70-75% of the HRR for the remainder of the program (Tsai et al., 2019). HRmax for male will be determined from equation based on Gellish et al., (2007) = 207-0.7(age), HRmax for female will be determined from equation based on Gulati et al., (2010) = 206-0.88(age). Resting heart rate will be determined based on the first visit (baseline assessment) and verified prior to start of each exercise session. Each aerobic exercise session involved a 5-minute warm-up period, followed by 30 minutes of continuous brisk walking at an intensity that would maintain the heart rate within the assigned training range, followed by 5 minutes of stretching. If rest is requested, an appropriate rest period will be included in the 30-minute walk session.	Other: Exercise training; Participation will last approximately 18 weeks (2 weeks of familiarization and assessment, 12 weeks of exercise intervention, and 4 weeks of follow-up). Participants will be randomized into three groups, either cycling group, strength training group or control group. Those in the cycling group and strength training group will undergo exercise intervention for about 2 sessions per week for 12 weeks (total 24 times) and will be followed for 4 weeks. The study will involve 28 visits. All groups will continue usual care at Singapore General Hospital. The control group will have usual care only during the duration of this study.
No Intervention: Control; The control group will continue their usual care from Singapore General Hospital during the period of this study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral blood flow	Participants will be equipped with a mobile functional near-infrared spectroscopy (fNIRS) device over their forehead. This device is used to detect changes in blood flow in the front area of the brain. Unit: the standard physiological units for brain perfusion: milliliters of blood per 100 grams of brain tissue per minute. Higher values indicate greater perfusion	Before 12-week intervention, immediately after 12-week intervention, and 4 weeks after intervention has ended

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive function	Montreal Cognitive Assessment test: scores for mild cognitive impairment is from 19 to 25. Higher scores indicate worse cognitive function	Before 12-week intervention, immediately after 12-week intervention, and 4 weeks after intervention has ended
Physical function	Timed Up and Go test: to measure balance. Unit: time in seconds. Lower values indicate better mobility and balance	Before 12-week intervention, immediately after 12-week intervention, and 4 weeks after intervention has ended
Physical characteristic	Body fat percentage. Unit: percentage (%). Higher values indicate greater proportion of fat mass in the body composition	Before 12-week intervention, immediately after 12-week intervention, and 4 weeks after intervention has ended
Level of depression	Patient Health Questionnaire-9 is a 9-item tool used to screen for and measure the severity of depression. Each item is scored on a scale from 0 (Not at all) to 3 (Nearly every day). Minimum Score: 0 (Indicates no depressive symptoms). Maximum Score: 27 (Indicates severe depression)	Before 12-week intervention, immediately after 12-week intervention, and 4 weeks after intervention has ended
Level of disability	The World Health Organization Disability Assessment Schedule measures general health and disability. Each 12 individual items are rated from 0 (None) to 4 (Extreme or cannot do). Minimum Score: 0 (No functional disability) Maximum Score: 48 (Full/maximum functional disability)	Before 12-week intervention, immediately after 12-week intervention, and 4 weeks after intervention has ended

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sociodemographic	• Self-report on sociodemographic characteristics, ethnicity, socioeconomic status, educational level, smoking status, alcohol intake, comorbidities, chronic medications, social activities, history of falls	Before 12-week intervention

Collaborators and Investigators

• Sponsor: Universiti Sains Malaysia
• Collaborators: Singapore General Hospital; National Institute of Education, Singapore

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: May 17, 2026
• First Posted (Actual): May 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Aerobic exercise; Ageing; Strength training; fNIRs
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: IRB-2025-838

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Data confidentiality Human subjects participation in this study will involve the collection, use and disclosure of data / health information in an individually identifiable form (or "Personal Data"). "Personal Data" means data about the participants, which makes them identifiable from (i) such data, and/or from (ii) other information which we have or likely have access to. This includes written, visual, video, audio data/recordings, medical conditions, medications, investigations and treatment history.

Personal Data and data collected for this study will be kept confidential and stored for a minimum of 10 years in a secure environment within NTU. Access will be restricted to the Principal Investigator, study team members, and School Administrators. The records, to the extent of the applicable laws and regulations, will not be made publicly available, in accordance with the NTU Privacy Statement.

Drug and device information, study documents

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