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

NCT07600034 | Not Yet Recruiting DMC

• 1 other identifier: IRB-2025-838
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Mild Cognitive Impairment (MCI)

Keywords

Aerobic exercise; Strength training; fNIRs; Ageing

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Cognitive function

  Before 12-week intervention, immediately after 12-week intervention, and 4 weeks after intervention has ended

• Physical function

  Before 12-week intervention, immediately after 12-week intervention, and 4 weeks after intervention has ended

• Physical characteristic

  Before 12-week intervention, immediately after 12-week intervention, and 4 weeks after intervention has ended

• Level of depression

  Before 12-week intervention, immediately after 12-week intervention, and 4 weeks after intervention has ended

• Level of disability

  Before 12-week intervention, immediately after 12-week intervention, and 4 weeks after intervention has ended

Other Outcomes (1)

• Sociodemographic

  Before 12-week intervention

Study Arms (3)

Resistance exercise

EXPERIMENTAL

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

Aerobic exercise

EXPERIMENTAL

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

Control

NO INTERVENTION

The control group will continue their usual care from Singapore General Hospital during the period of this study

Interventions

Exercise training OTHER

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.

Aerobic exercise; Resistance exercise

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Universiti Sains Malaysia: lead
• Singapore General Hospital: collaborator
• National Institute of Education, Singapore: collaborator

Study Sites (1)

National Institute of Education

Singapore, 637616, Singapore

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Exercise

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Postdoctoral fellow

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: May 20, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)