Effects of multi-domain lifestyle interventions on sarcopenia measures and blood biomarkers: secondary analysis of a randomized controlled trial of community-dwelling pre-frail and frail older adults.

Few studies have comprehensively described changes in blood biomarkers of the physiological responses underlying sarcopenia reduction associated with lifestyle interventions. In this study, we performed secondary analyses of data in a randomized controlled trial of multi-domain lifestyle interventions (6-month duration physical exercise, nutritional enrichment, cognitive training, combination and standard care control) among 246 community-dwelling pre-frail and frail elderly, aged ≥65 years, with and without sarcopenia. Appendicular lean mass (ALM), lower limb strength, gait speed, and blood levels of markers of muscle metabolism, inflammation, anti-oxidation, anabolic hormone regulation, insulin signaling, tissue oxygenation were measured at baseline, 3-month and 6-month post-intervention. Multi-domain interventions were associated with significant (p < 0.001) reduction of sarcopenia at 3-month and 6-month post-intervention, improved gait speed, enhanced lower limb strength, and were equally evident among sarcopenic participants who were slower at baseline than non-sarcopenic participants. Active intervention was associated with significantly reduced inflammation levels. Sarcopenia status and reduction were associated with blood biomarkers related to muscle metabolism, steroid hormone regulation, insulin-leptin signaling, and tissue oxygenation. Physical, nutritional and cognitive intervention was associated with measures of sarcopenia reduction, together with changes in circulating biomarkers of anabolic and catabolic metabolism underlying sarcopenia.

Assessment of Sarcopenia Among Community-Dwelling At-Risk Frail Adults Aged 65 Years and Older Who Received Multidomain Lifestyle Interventions: A Secondary Analysis of a Randomized Clinical Trial.

Importance: There is little understanding of the outcomes associated with active lifestyle interventions for sarcopenia among older persons. Objective: To determine the association of 6-month multidomain lifestyle interventions (physical exercise, nutritional enhancement, cognitive training, combined treatment, and standard care) with change in sarcopenia status and physical function among adults 65 years and older. Design, Setting, and Participants: Post hoc secondary analysis of a parallel-group randomized clinical trial conducted from September 1, 2012, to September 1, 2014, at community centers providing services to elderly individuals in Singapore. Participants included a subsample of 92 community-dwelling prefrail or frail older persons with sarcopenia aged 65 years and older. Data were analyzed from June 1, 2017, to January 1, 2018. Interventions: The 5 intervention groups were a 6-month duration of physical exercise that included resistance and balance training, nutritional enhancement with a commercial oral nutrition supplement formula, cognitive training, a combination of the preceding 3 interventions, and standard care (control). Main Outcomes and Measures: Primary outcomes were changes in sarcopenia status and its components, appendicular skeletal muscle index (ASMI), knee extension strength (KES), and gait speed (GS) at 3 months and 6 months following the intervention. Sarcopenia was defined as the presence of both low ASMI and low KES and/or GS. Results: In 92 participants with sarcopenia, the mean (SD) age was 70.0 (4.7) years and 59 (64.1%) were female. Seventy-eight participants received active interventions and 14 received standard care. Of 92 total participants, the number who remained sarcopenic was reduced to 48 (of 73) after 3 months and 51 (of 75) after 6 months of intervention, indicating that 25 of 92 participants (27.2%) experienced sarcopenia reduction at 3 months and 24 of 92 (26.1%) had sarcopenia reduction at 6 months. Low KES was present in 88 of 92 patients (95.6%), and low GS in 30 of 92 patients (32.6%) at baseline. Among the components of sarcopenia, GS had the greatest change associated with active interventions, with 22 of 30 participants (73.3%) free of low GS at 6 months; in comparison, 17 of 88 participants (19.3%) were free of low KES at 6 months and 7 of 92 participants (7.6%) were free of low ASMI at 6 months. Men experienced greater reduction in sarcopenia than women (χ2 = 5.925; P = .02), as did those with younger age (t = -2.078; P = .04) or higher ASMI (mean [SD] ASMI, 5.74 [0.77] vs 5.14 [0.77] kg/m2; P = .002). Participants in the active intervention group experienced statistically significant decreases in sarcopenia score and its components at 3 months and 6 months from baseline (F = 14.138; P < .001), but the intervention was not associated with significant differences in ASMI, KES, and GS vs standard care. Conclusions and Relevance: This study suggests that older persons with sarcopenia are responsive to the effects of multidomain lifestyle interventions. Sarcopenia reduction was most pronounced through improved gait speed, and occurred more among those who were male, were younger, or had greater muscle mass.

Cognitive Effects of Multi-Domain Interventions Among Pre-Frail and Frail Community-Living Older Persons: Randomized Controlled Trial.

Background: Cognitive, physical, and nutritional interventions may produce different cognitive effects for different groups of older persons. We investigated simultaneously the cognitive outcomes of cognitive, physical, and nutritional interventions singly and in combinations in older persons with the physical frailty phenotype at particular risk of cognitive decline. Method: Pre-frail and frail participants were randomly allocated to 24 weeks nutritional supplementation (N = 49), physical training (N = 48), cognitive training (N = 50), combination intervention (N = 49), or usual care control (N = 50). Cognitive domain and global functions were assessed at baseline (0M), 6 month (6M), and 12 month (12M). Results: The control group showed declines in z-scores (from -0.100 to -0.244) of all domains. The cognitive training compared to control group showed the greatest increase in global cognition at 6M (0.094 vs -0.174, p = .006) and 12M (0.099 vs -0.142, p = .002), immediate memory at 6M (0.164 vs -0.211, p = .010) and 12M (0.182 vs -0.142, p = .040), delayed memory at 6M (p = .010), and attention at 6M (p = .025). Nutritional intervention showed benefits at 6M for immediate memory (p = .028) and delayed memory (p = .024), but physical training showed no positive effects. The combination group showed the greatest increase for visuospatial construction at 6M (0.215 vs -0.141, p = .010) and 12M (0.166 vs -0.180, p = .016), and for global cognition at 12M (p = .016) and language at 12M (p = .023). Conclusion: Among frail older persons, cognitive training conferred the greatest cognitive benefits. Nutritional and physical interventions singly were associated with modest short-term or no cognitive benefits, but their combined effects on visuospatial construction should be further investigated.

Nutritional, Physical, Cognitive, and Combination Interventions and Frailty Reversal Among Older Adults: A Randomized Controlled Trial.

BACKGROUND: It is important to establish whether frailty among older individuals is reversible with nutritional, physical, or cognitive interventions, singly or in combination. We compared the effects of 6-month-duration interventions with nutritional supplementation, physical training, cognitive training, and combination treatment vs control in reducing frailty among community-dwelling prefrail and frail older persons. METHODS: We conducted a parallel group, randomized controlled trial in community-living prefrail and frail old adults in Singapore. The participants' mean age was 70.0 years, and 61.4% (n = 151) were female. Five different 6-month interventions included nutritional supplementation (n = 49), cognitive training (n = 50), physical training (n = 48), combination treatment (n = 49), and usual care control (n = 50). Frailty score, body mass index, knee extension strength, gait speed, energy/vitality, and physical activity levels and secondary outcomes (activities of daily living dependency, hospitalization, and falls) were assessed at 0 months, 3 months, 6 months, and 12 months. RESULTS: Frailty score and status over 12 months were reduced in all groups, including control (15%), but were significantly higher (35.6% to 47.8%) in the nutritional (odds ratio [OR] 2.98), cognition (OR 2.89), and physical (OR 4.05) and combination (OR 5.00) intervention groups. Beneficial effects were observed at 3 months and 6 months, and persisted at 12 months. Improvements in physical frailty domains (associated with interventions) were most evident for knee strength (physical, cognitive, and combination treatment), physical activity (nutritional intervention), gait speed (physical intervention), and energy (combination intervention). There were no major differences with respect to the small numbers of secondary outcomes. CONCLUSIONS: Physical, nutritional, and cognitive interventional approaches were effective in reversing frailty among community-living older persons.