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.
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.