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

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.

Study Overview

• Status: Completed
• Conditions: Age-related Cognitive Decline; Age-related Physiology Decline
• Intervention / Treatment: Behavioral: Multi-domain intervention

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 112
    • Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual care group; Provide conventional health educations in every three-month interval
Experimental: Multidomain intervention group; The multidomain intervention program is designed as structural training sessions of 2-hour training sessions two times per week.	Behavioral: Multi-domain intervention; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Change in brain structures on MRI	Change in brain structures from baseline to 12 months in all participants	baseline, 12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Follistatin	Change in Follistatin 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
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 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 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
Change in cognitive ability	Change in cognitive function measure by MoCA ranged 0-30, higher values represent a better condition	baseline, 6, 12 month

Collaborators and Investigators

• Sponsor: National Yang Ming University
• Collaborators: National Science and Technology Council
• Investigators: Study Director: Liang-Kung Chen, M.D., PhD, Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Actual): July 30, 2023
• Study Completion (Actual): July 30, 2023

Study Registration Dates

• First Submitted: April 13, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: dementia; neuroimaging; biomarkers; frailty; aging; multidomain intervention; cognitive impairment; skeletal muscle; physio-cognitive decline syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: YM109161F

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No