A Novel Multi-Modal Approach to Promote Functional Outcomes in Cognitively Frail Older Adults

Обзор

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?

Подробное описание

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)

Вмешательства

• Устройство Theta 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 sti
• Поведенческое Aerobic 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 w

Первичные конечные точки

• Montreal Cognitive Assessment [Срок оценки: Baseline, 3 months, and 6 months]
• Short Physical Performance Battery [Срок оценки: Baseline, 3 months, and 6 months]
• Pictorial Fit-Frail Scale [Срок оценки: Baseline, 3 months, and 6 months]

Вторичные конечные точки (12)

• Six Minutes Walking Test [Срок оценки: Baseline, 3 months, and 6 months]
• Timed-Up-and-Go Test [Срок оценки: Baseline, 3 months, and 6 months]
• Task Switch Test [Срок оценки: Baseline, 3 months, and 6 months]
• Digit Span Test [Срок оценки: Baseline, 3 months, and 6 months]
• Digit Symbol Substitution Test [Срок оценки: Baseline, 3 months, and 6 months]
• Stroop Test [Срок оценки: Baseline, 3 months, and 6 months]
• Trail Making Test [Срок оценки: Baseline, 3 months, and 6 months]
• Sit to stand [Срок оценки: Baseline, 3 months, and 6 months]
• cortical and subcortical volume [Срок оценки: Baseline, 3 months, and 6 months]
• Resting State-Functional Connectivity-Functional MRI [Срок оценки: Baseline, 3 months, and 6 months]
• Physical Activity Scale for the Elderly [Срок оценки: Baseline, 3 months, and 6 months]
• Geriatric Depression Scale [Срок оценки: Baseline, 3 months, and 6 months]

Критерии участия

Критерии включения

• be between 60 and 90 years old;
• scored < 9/12 on the SPPB;
• scored >18/30 on the MoCA;
• scored >9/42 on the PFFS;
• lived in the community;
• be able to ambulate up to four meters with or without assistive devices;
• be able to provide written informed consent on their own behalf;
• can understand verbal and written Cantonese and/or English.

Критерии исключения

• have magnetic resonance imaging (MRI) contraindications;
• have aerobic exercise contraindications;
• have transcranial magnetic stimulation contraindications;
• be diagnosed with neurodegenerative conditions (i.e., dementia, Parkinson's, Alzheimer's disease, Amyotrophic lateral sclerosis, and stroke);
• live in a nursing home or other care facilities/institutions;
• 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.
• have a history indicative of carotid sinus sensitivity (i.e., falls due to loss of consciousness);
• cancer and undergo radiation therapy.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Гонконг · 1 центр

• The Hong Kong Polytechnic University, Department of Rehabilitation Sciences — Гонконг

Идентификаторы

NCT: NCT07497334 · HSEARS20240614001 · P0048639

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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