Frailty at Older Adults, Mild Cognitive Impairment
Conditions
Keywords
cognitive frailty, cTBS, iTBS, aerobic exercise, fMRI
Brief summary
The goal of this clinical trial is to explore the effects of intermittent theta burst stimulation (iTBS) primed with theta burst stimulation (cTBS), on top of aerobic exercise, on cognitive function, mobility, and brain activity in older adults with cognitive frailty. Understanding these effects will help us develop intervention models that benefit cognitively frail older adults. The main questions it aims to answer are: 1. Does the combination of iTBS primed with cTBS and aerobic exercise lead to greater improvements in cognition and mobility in older adults with cognitive frailty compared to non-priming iTBS and sham stimulation? 2. What are the neural mechanisms responsible for the improvements in cognition and mobility associated with the combination of iTBS primed with cTBS and aerobic exercise in older adults with cognitive frailty?
Detailed description
Objectives: To compare the effects of intermittent theta burst stimulation (iTBS) primed with continuous theta burst stimulation (cTBS), nonpriming iTBS, and sham stimulation on top of aerobic exercise in terms of improving cognitive function, mobility, brain structure, and brain function in older adults with cognitive frailty. Hypothesis to be tested: We hypothesize that iTBS primed with cTBS can maximize the induction of therapeutically beneficial metaplasticity, and that this will be reflected in improved brain structure and brain function, thereby enabling superior cognitive function and mobility improvement in older adults with cognitive frailty. Design and subjects: A randomized controlled trial involving 60 older adults with cognitive frailty. Study instruments: Transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI). Interventions: Participants will be randomly allocated to receive a 39-session intervention with different TBS protocols (i.e., cTBS+iTBS, sham cTBS+iTBS, and sham cTBS+sham iTBS), delivered 3 times per week for 3 months. All participants will receive 60 minutes of aerobic exercise after each stimulation session for 6 months. Main outcome measures: comprehensive neuropsychological battery covering major executive function (i.e., selective attention/response inhibition, psychomotor speed, set shifting), working memory, and verbal fluency; (2) mobility function evaluated via SPPB, Timed-Up-and-GO (TUG) test, functional gait analysis (i.e., gait speed, gait variability). Secondary outcomes: underlying neural mechanisms of intervention-induced benefits will be assessed via functional and structural magnetic resonance imaging. Data analysis: Analysis of variance (ANOVA)
Interventions
DEVICETheta burst stimulation
Theta burst stimulation (TBS) will be administered using a figure-of-eight shaped cooling coil (Cool-B65 A/P), which generates auditory "clicks" for sham stimulation that are similar to those produced by active repetitive transcranial magnetic stimulation (rTMS). The placement of the coil will be guided by a navigation system (LOCALITE® TMS Navigator, Germany) using each participant's baseline T1-weighted MRI scans. TBS is a powerful form of rTMS. Standard 600-pulse intermittent theta burst stimulation (iTBS) can enhance corticomotor excitability, whereas standard 600-pulse continuous theta burst stimulation (cTBS) can suppress it.
BEHAVIORALAerobic exercise
The aerobic exercise sessions will include a 10-minute warm-up, followed by 40 minutes of brisk walking and/or stationary exercises without weights, and will conclude with a 10-minute cooldown. The intensity of the aerobic exercise will be monitored using heart rate, starting at 40% of the age-specific heart rate reserve (HRR), which is calculated using the formula: 207 - (0.7 x age). Over the initial 12 weeks, the intensity will be gradually increased until the HRR reaches 65%, and this level will be maintained until the end of the trial.
Sponsors
The Hong Kong Polytechnic University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. be between 60 and 90 years old; 2. scored \< 9/12 on the SPPB; 3. scored \>18/30 on the MoCA; 4. scored \>9/42 on the PFFS; 5. lived in the community; 6. be able to ambulate up to four meters with or without assistive devices; 7. be able to provide written informed consent on their own behalf; 8. can understand verbal and written Cantonese and/or English.
Exclusion criteria
1. have magnetic resonance imaging (MRI) contraindications; 2. have aerobic exercise contraindications; 3. have transcranial magnetic stimulation contraindications; 4. be diagnosed with neurodegenerative conditions (i.e., dementia, Parkinson's, Alzheimer's disease, Amyotrophic lateral sclerosis, and stroke); 5. live in a nursing home or other care facilities/institutions; 6. bed taking fixed dose of medication or had been taking medications known to potentially affect cognitive and physical function (e.g., psychotropic medications), as identified through a review of their medication lists recorded in the health software. Medications were categorized by properties (e.g., antipsychotics, antidepressants, etc.) to inform eligibility decisions. 7. have a history indicative of carotid sinus sensitivity (i.e., falls due to loss of consciousness); 8. cancer and undergo radiation therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montreal Cognitive Assessment | Baseline, 3 months, and 6 months | General cognitive function will be measured by Montreal Cognitive Assessment |
| Short Physical Performance Battery | Baseline, 3 months, and 6 months | Mobility will be measured by Short Physical Performance Battery |
| Pictorial Fit-Frail Scale | Baseline, 3 months, and 6 months | The assessment of frailty in older adults will be conducted using the Pictorial Fit-Frail Scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Six Minutes Walking Test | Baseline, 3 months, and 6 months | The Six Minutes Walking Test is a standard assessment for mobility |
| Timed-Up-and-Go Test | Baseline, 3 months, and 6 months | The Timed-Up-and-Go Test is a standard assessment for mobility and gait |
| Task Switch Test | Baseline, 3 months, and 6 months | The Task Switch Test is a standard assessment for executive function |
| Digit Span Test | Baseline, 3 months, and 6 months | The Digit Span Test is a standard assessment for executive function |
| Digit Symbol Substitution Test | Baseline, 3 months, and 6 months | The Digit Symbol Substitution Test is a standard assessment for executive function |
| Stroop Test | Baseline, 3 months, and 6 months | The Stroop Test is a standard assessment for executive function |
| Trail Making Test | Baseline, 3 months, and 6 months | The Trail Making Test is a standard assessment for executive function |
| Sit to stand | Baseline, 3 months, and 6 months | The Sit to stand is a standard assessment for mobility |
| cortical and subcortical volume | Baseline, 3 months, and 6 months | Cortical and subcortical volume will be examined in all participants using MRI. Participants will undergo structural MRI on the 3T Siemens scanner at the University Research Facility in Behavioral and Systems Neuroscience. Participants will complete T1 and T2 high resolution anatomical scans. |
| Resting State-Functional Connectivity-Functional MRI | Baseline, 3 months, and 6 months | Participants will be instructed to rest with eyes open for approximately 12 minutes. This will allow the investigators to examine activation in the resting state network. |
| Physical Activity Scale for the Elderly | Baseline, 3 months, and 6 months | Physical activity will be assessed by Physical Activity Scale for the Elderly |
| Geriatric Depression Scale | Baseline, 3 months, and 6 months | Depression will be measured by Geriatric Depression Scale |
| Fatigue Severity Scale | Baseline, 3 months, and 6 months | Physical fatigue will be measured by Fatigue Severity Scale |
| Functional Comorbidity Index | Baseline, 3 months, and 6 months | Total number of comorbid conditions will be assessed through the Functional Comorbidity Index |
| Functional Activities Questionnaire | Baseline, 3 months, and 6 months | The difficulties in activities of daily living will be assessed using the Functional Activities Questionnaire. |
Countries
Hong Kong
Contacts
CONTACTJINGYI WU, MSc
PRINCIPAL_INVESTIGATORChun Liang HSU, PhD
The Hong Kong Polytechnic University
Outcome results
None listed