Brain Aging: Muscle-to-brain Axis Modulates Physio-cognitive Decline

Study Overview
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Brief Summary
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The primary goal is to develop a multidomain intervention program focused on preserving global or regional brain volume and functions while simultaneously improving physical mobility and cognitive functions in older individuals with mobility frailty. This initiative seeks to unravel the brain-muscle axis mechanisms contributing to the accelerated functional declines observed in older populations. Moreover, our objective includes examining the relationships between the intervention and a broad spectrum of clinical characteristics, phenotypic traits, biochemical profiles, myokines, proteomics, metabolomics, brain imaging, and our previously identified discoveries involving exosomal miRNA.

Detailed Description
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This study is a randomized controlled trial of 12-month multidomain intervention program among community-living older adults with early physical or cognitive impairments. Inclusion criteria are: (1) community-dwelling adults aged ≥ 65 years, (2) slow gait speed (<1 m/s in 6-meter walk test) or weakness (dominant handgrip strength <28 kg in men, <18 kg in women); subjects with the following conditions will be excluded: (1) established diagnosis of dementia, Parkinsonism or other neurodegenerative disease (2) disable status: mobility-limiting conditions, (3) active, acute diseases receiving treatment, such as cancer, heart failure, COPD and so on, (4) estimated life expectancy <12 months, (5) current nursing home residents.

Official Title
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Brain Aging: Muscle-to-brain Axis Modulates Physio-cognitive Decline

Conditions
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Age-related Cognitive Decline, Age-related Physiology Decline

Intervention / Treatment
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* Behavioral: Multi-domain intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged ≥ 65 years slow gait speed (<1 m/s in 6-meter walk test) or weakness (dominant handgrip strength <28 kg in men, <18 kg in women) Exclusion Criteria: established diagnosis of dementia, Parkinsonism or other mobility-limiting, disable conditions active, acute diseases receiving treatment, such as cancer, heart failure, COPD and so on estimated life expectancy <12 months current nursing home residents

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual care group<br>Provide conventional health educations in every three-month interval | |
| Experimental: Multidomain intervention group<br>The multidomain intervention program is designed as structural training sessions of 2-hour training sessions two times per week. | Behavioral: Multi-domain intervention<br>* Each session comprises of 45 minutes physical fitness activities targeting on muscle strength, balance, and flexibility; 1-hour cognitive training primarily on reasoning and memory exercises; and 15-minute for nutritional advices based on national diet guidelines for older adults<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in brain structures on MRI | Change in brain structures from baseline to 12 months in all participants | baseline, 12 month | 
| Change in Physical performance | Change in hand-grip strength (kg), six-meter walking speed (m/s), and 5 times sit to stand test from baseline to 12 months in all participants | baseline, 6, 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Life quality SF12 | measured by the 12-Item Short Form Health Survey (SF-12). | baseline, 6, 12 month | 
| Change in Complete blood count | Change in Complete blood count from baseline to 12 months in all participants | baseline, 6, 12 month | 
| Change in Nutrition intake | measured by Mini-nutritional assessment questionnaire. ranged 0-30, higher values represent a better condition | baseline, 6, 12 month | 
| Change in depression | measured by the Center for Epidemiological Studies-Depression (CES-D) ranged 0-60, higher values represent a worse condition | baseline, 6, 12 month | 
| Change in cognitive ability | Change in cognitive function measure by MoCA ranged 0-30, higher values represent a better condition | baseline, 6, 12 month | 
| Change in International Physical Activity Questionnaire (IPAQ) | Change in physical activity measured by IPAQ, indicates that spent being physically active than the prior 7 days.There are no established thresholds for presenting MET-minutes, the IPAQ Research Committee proposes that reported as comparisons of median values and interquartile ranges for different populations from baseline to 12 months in all participants. The higher values represent a better activity. | baseline, 6, 12 month | 
| Change in Vitamin D3 25-OH | Change in Vitamin D3 25-OH concentration from baseline to 12 months in all participants | baseline, 6, 12 month | 
| Change in DHEA-S | Change in DHEA-S concentration from baseline to 12 months in all participants | baseline, 6, 12 month | 
| Change in IGF-1 | Change in IGF-1 concentration from baseline to 12 months in all participants | baseline, 6, 12 month | 
| Change in Homocysteine | Change in Homocysteine concentration from baseline to 12 months in all participants | baseline, 6, 12 month | 
| Change in hs-CRP | Change in hs-CRP concentration from baseline to 12 months in all participants | baseline, 6, 12 month | 
| Change in Zinc | Change in Zinc concentration from baseline to 12 months in all participants | baseline, 6, 12 month | 
| Change in TSH | Change in TSH concentration from baseline to 12 months in all participants | baseline, 6, 12 month | 
| Change in Myostatin | Change in Myostatin concentration from baseline to 12 months in all participants | baseline, 6, 12 month | 
| Change in Activing A | Change in Activing A concentration from baseline to 12 months in all participants | baseline, 6, 12 month | 
| Change in Follistatin | Change in Follistatin concentration from baseline to 12 months in all participants | baseline, 6, 12 month | 
| Change in Relative appendicular skeletal muscle index (RASM) | Change in RASM from baseline to 12 months in all participants | baseline, 6, 12 month | 
| Change in body fat % | Change in body fat % from baseline to 12 months in all participants | baseline, 6, 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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frailty, cognitive impairment, physio-cognitive decline syndrome, dementia, biomarkers, skeletal muscle, aging, neuroimaging, multidomain intervention