Assessing Causality of the Association Between Exercise and Neurocognitive Gains

Brief Summary: The aim of this project is to examine:

1. The effects of a community based square stepping exercise programme on cognitive and physical functions in older adults.
2. The effects of a community based square stepping exercise programme on neuroplasticity in older adults.
3. The effects of a community based square stepping exercise programme on structural and functional brain changes in older adults.
4. The relationship between exercise-induced changes in neuroplasticity, structural and functional brain activations, and cognitive and physical gains in older adults.

Study Overview

• Status: Completed
• Conditions: Aging Well
• Intervention / Treatment: Other: exercise

Detailed Description

It is well known regular exercise produces both physical and cognitive benefits. Emerging evidence suggests that physical movements or exercise that have concurrent cognitive demands may have more profound effects on cognitive and brain health outcomes. One training program that incorporates these components is the square stepping exercise (SSE). First demonstrated in Japan, this community-based paradigm has already shown to reduce falls risk and presents as a convenient exercise modality for older adults, that can be conducted in a group setting or even the home. The current project aims to examine the efficacy of this SSE community programme in a Singapore context on cognitive and physical health in older adults. This study also aims to quantify the neural correlates underpinning any observed improvements in cognitive and physical function. Specifically, this project will measure indices of neuroplasticity via structural and functional magnetic resonance imaging, transcranial magnetic stimulation, and electroencephalography.

Sample size estimation: n=80 for behavioural primary outcome measures and n=40 subset of larger sample for neuroimaging and neuroplasticity secondary outcome measures [anticipated].

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • Nanyang Technological University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Older adults aged 55-80
• Sedentary, defined as exercise less than 3 times per week for 30 minutes

Exclusion Criteria:

• Square stepping exercise:
• Medical conditions preventing them from movement and/or exercise
• Psychiatric conditions
• Cognitive impairment of dementia
• Upper and/or lower limb injuries in the past 6 months
• History of falls in the past 6 months
• Current smokers
• Neuroimaging (all the above in addition to the following)
• Patients who have conductive, ferromagnetic, or magnet-sensitive metals implanted in head (e.g., aneurysm clip, stent).
• Implanted medical device: e.g., cardiac implants, cochlear implant, aneurysm clips, cardiac pacemaker etc.
• Non-removable metal braces or retainer (dental fillings ok).
• Permanent tattoos on head.
• Deep brain stimulators.
• Previous brain surgery or injury.
• Patient with epilepsy or any other seizure history, or immediate family history of epilepsy.
• Clinical EEG that was abnormal or where seizure activity had not been ruled out.
• Patients with history of head injury with loss of consciousness are to be investigated about the history if/before being recruited.
• Diagnosis or possibility of neurological disorder (including stroke).
• Psychiatric condition.
• Major or unstable medical condition/surgery.
• Current or suspected pregnancy or lactation.
• Illicit drug use in the last 7 days.
• Alcohol use in the last 12 hours or more than 3 standard drinks in last 24 hours.
• Recent insomnia or severe sleep deprivation.
• Participation in another study involving brain stimulation (e.g., TMS, TDCS) in the past 7 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise-Cognition; Square Stepping Exercise	Other: exercise; Square stepping exercise
No Intervention: No exercise; Passive control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Go-No-Go task change	Error rate: Number of "Go" responses on "No-Go" trials.	Baseline (week 0), mid-intervention (week 7 after session 12), post-intervention (week 13 after session 24)
Stroop task colour words and colour blocks	Average response time (reaction time) for the correct colour word incongruent trials.	Baseline (week 0), mid-intervention (week 7 after session 12), post-intervention (week 13 after session 24)
N-Back task change	Number of correct responses (hits)	Baseline (week 0), mid-intervention (week 7 after session 12), post-intervention (week 13 after session 24)
Trail Making Test ((TMT) change	B:A: Divide the time taken for TMT B by TMT A	Baseline (week 0), mid-intervention (week 7 after session 12), post-intervention (week 13 after session 24)
Digit Span task change	Maximum accurate span length for Digit Span Forward Maximum accurate span length for Digit Span Reverse	Baseline (week 0), mid-intervention (week 7 after session 12), post-intervention (week 13 after session 24)
Modified Card Sorting task change	Total number of perseverative errors	Baseline (week 0), mid-intervention (week 7 after session 12), post-intervention (week 13 after session 24)
Static balance (single leg) change	Duration required to perform single leg stance on left and right legs	Baseline (week 0), post-intervention (week 13 after session 24)
Temporal gait parameters change	11-meter gait test to examine gait speed	Baseline (week 0), post-intervention (week 13 after session 24)
Motor learning change	Probabilistic Serial Reaction Time Task: learning index, computed using reaction time	Baseline (week 0), post-intervention (week 13 after session 24)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cortical thickness	T1 and T2 weighted images	Baseline (week 0), post-intervention (week 13 after session 24)
Change in grey matter volume	T1 and T2 weighted images	Baseline (week 0), post-intervention (week 13 after session 24)
Change in structural topography	T1 and T2 weighted images	Baseline (week 0), post-intervention (week 13 after session 24)
Change in white matter integrity	Diffusion Tensor Imaging	Baseline (week 0), post-intervention (week 13 after session 24)
Change in white matter connectivity	Diffusion Tensor Imaging	Baseline (week 0), post-intervention (week 13 after session 24)
Change in functional connectivity	Resting state functional magnetic resonance imaging	Baseline (week 0), post-intervention (week 13 after session 24)
Brain plasticity changes	Changes in transcranial magnetic stimulation (TMS) induced motor evoked potential amplitudes in response to theta-burst stimulation protocol	Baseline (week 0), post-intervention (week 13 after session 24)
Brain plasticity changes	Changes in transcranial magnetic stimulation (TMS)-evoked potentials recorded from electroencephalography (EEG)	Baseline (week 0), post-intervention (week 13 after session 24)
Brain plasticity changes	Changes in power spectral density and coherence recorded from electroencephalography (EEG)	Baseline (week 0), post-intervention (week 13 after session 24)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective vitality scale change	5-item vitality score (7-point scale, higher score greater wellbeing outcome)	Baseline (week 0), post-intervention (week 13 after session 24)
Heart rate variability change	Measured through deep breathing protocol with electrocardiography (ECG)	Baseline (week 0), post-intervention (week 13 after session 24)
Falls risk change	Falls efficiency scale, 16-item and 4-point scale. Lower score equates to more fear of falling and less confident during daily activities.	Baseline (week 0), post-intervention (week 13 after session 24)
Social engagement and cohesion	Physical Activity Group Environment Questionnaire: 21 items on 9-point scale. Higher scores = more social connection. The community social participation scale will be used as a covariate when analyzing this scale.	Baseline (week 0), post-intervention (week 13 after session 24)
Change in mood (related to movement)	Anxiety and depression subscale of Movement Specific Reinvestment Scale: 10-item, 6-point for anxiety and depression around movement. Higher scores = more symptoms of anxiety and depression.	Baseline (week 0), post-intervention (week 13 after session 24)

Collaborators and Investigators

• Sponsor: Nanyang Technological University

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2022
• Primary Completion (Actual): April 4, 2023
• Study Completion (Actual): April 4, 2023

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: August 19, 2022
• First Posted (Actual): August 22, 2022

Study Record Updates

• Last Update Posted (Actual): May 31, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: exercise; older adults; cognition; neuroplasticity; healthy aging
• Other Study ID Numbers: MOE2019-T2-1-019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Only de-identified data will be shared after publication and upon request. Request for data needs to justify use of data.
• IPD Sharing Time Frame: 6 months after publication
• IPD Sharing Access Criteria: Request needs to be made to the PI with clear plan for the use of data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No