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

The main goal is to develop an enhanced intervention program that can persistently maintain intervention effects with measurement of clinical characteristics, phenotypic features, together with biochemical profiles, myokines, proteomics, metabolomics brain imaging, and our previous findings of exosomal miRNA and to correlate changes of the biomarkers to neuroimaging. The linkage between both positive (irisin) and negative regulators (myostatin, miR-29b-3p) with structural brain imaging by a randomized controlled trial is the key novelty with strongest evidence strength in human study.

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), (3) subjective cognitive declines; subjects with the following conditions will be excluded: (1) established diagnosis of dementia, Parkinsonism or other mobility-limiting conditions, (2) active diseases receiving treatment, such as cancer, heart failure, COPD and so on, (3) estimated life expectancy <12 months, (4) current nursing home residents.

frailty, cognitive impairment, physio-cognitive decline syndrome, dementia, biomarkers, skeletal muscle, aging, neuroimaging, multidomain intervention

The multidomain intervention program is designed as structural training sessions of 2-hour training sessions two times per week.

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

Change in hand-grip strength (kg), six-meter walking speed (m/s) from baseline to 12 months in all participants

measured by Mini-nutritional assessment questionnaire. ranged 0-30, higher values represent a better condition

measured by the Center for Epidemiological Studies-Depression (CES-D) ranged 0-60, higher values represent a worse condition

Change in cognitive function measure by MoCA ranged 0-30, MMSE ranged 0-30, higher values represent a better condition

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.

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) subjective cognitive declines Exclusion Criteria: established diagnosis of dementia, Parkinsonism or other mobility-limiting conditions active diseases receiving treatment, such as cancer, heart failure, COPD and so on estimated life expectancy <12 months current nursing home residents