Optimal management of sarcopenia

Sarcopenia is the progressive generalized loss of skeletal muscle mass, strength, and function which occurs as a consequence of aging. With a growing older population, there has been great interest in developing approaches to counteract the effects of sarcopenia, and thereby reduce the age-related decline and disability. This paper reviews (1) the mechanisms of sarcopenia, (2) the diagnosis of sarcopenia, and (3) the potential interventions for sarcopenia. Multiple factors appear to be involved in the development of sarcopenia including the loss of muscle mass and muscle fibers, increased inflammation, altered hormonal levels, poor nutritional status, and altered renin–angiotensin system. The lack of diagnostic criteria to identify patients with sarcopenia hinders potential management options. To date, pharmacological interventions have shown limited efficacy in counteracting the effects of sarcopenia. Recent evidence has shown benefits with angiotensin-converting enzyme inhibitors; however, further randomized controlled trials are required. Resistance training remains the most effective intervention for sarcopenia; however, older people maybe unable or unwilling to embark on strenuous exercise training programs

Effect of Angiotensin System Inhibitors on Physical Performance in Older People - A Systematic Review and Meta-Analysis

Objective: Preclinical and observational data suggest that angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) may be able to improve physical performance in older people via direct and indirect effects on skeletal muscle. We aimed to summarize current evidence from randomised controlled trials in this area. Design: Systematic review and meta-analysis. Setting and Participants: Randomized controlled trials enrolling older people, comparing ACEi or ARB to placebo, usual care or another antihypertensive agent, with outcome data on measures of physical performance. Methods: We searched multiple electronic databases without language restriction between inception and the end of February 2020. Trials were excluded if the mean age of participants was <65 years or treatment was targeting specific diseases known to affect muscle function (for example heart failure). Data were sought on measures of endurance and strength. Standardized mean difference (SMD) treatment effects were calculated using random-effects models with RevMan software. Results: Eight trials (952 participants) were included. Six trials tested ACEi, 2 trials tested ARBs. The mean age of participants ranged from 66 to 79 years, and the duration of treatment ranged from 2 months to 1 year. Trials recruited healthy older people and people with functional impairment; no trials specifically targeted older people with sarcopenia. Risk of bias for all trials was low to moderate. No significant effect was seen on endurance outcomes [6 trials, SMD 0.04 (95% CI –0.22 to 0.29); P =.77; I2 = 53%], strength outcomes [6 trials, SMD –0.02 (95% CI –0.18 to 0.14), P =.83, I2 = 21%] or the short physical performance battery [3 trials, SMD –0.04 (95% CI –0.19 to 0.11), P =.60, I2 = 0%]. No evidence of publication bias was evident on inspection of funnel plots. Conclusions and Implications: Existing evidence does not support the use of ACE inhibitors or angiotensin receptor blockers as a single intervention to improve physical performance in older people

Associations between frailty, physical performance, and renal biomarkers in older people with advanced chronic kidney disease

Acknowledgments With thanks to the recruiting teams and participants who took part in the BiCARB trial. GS and MDW acknowledge support from the NIHR Newcastle Biomedical Research CentrePeer reviewedPublisher PD

Spironolactone for People Age 70 Years and Older With Osteoarthritic Knee Pain:A Proof‐of‐Concept Trial

Objective: To determine whether spironolactone could benefit older people with osteoarthritis (OA), based on a previous study showing that spironolactone improved quality of life. Methods: This parallel-group, randomized, placebo-controlled, double-blind trial randomized community-dwelling people ages ≥70 years with symptomatic knee OA to 12 weeks of 25 mg daily oral spironolactone or matching placebo. The primary outcome was between-group difference in change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores. Secondary outcomes included WOMAC stiffness and physical function subscores, EuroQol 5-domain (EQ-5D) 3L score, and mechanistic markers. Analysis was by intent to treat, using mixed-model regression, adjusting for baseline values of test variables. Results: A total of 421 people had eligibility assessed, and 86 were randomized. Mean ± SD age was 77 ± 5 years and 53 of 86 (62%) were women. Adherence to study medication was 99%, and all participants completed the 12-week assessment. No significant improvement was seen in the WOMAC pain score (adjusted treatment effect 0.5 points [95% confidence interval (95% CI) - 0.3, 1.3]; P = 0.19). No improvement was seen in WOMAC stiffness score (0.2 points [95% CI -0.6, 1.1]; P = 0.58), WOMAC physical function score (0.0 points [95% CI -0.7, 0.8]; P = 0.98), or EQ-5D 3L score (0.04 points [95% CI -0.04, 0.12]; P = 0.34). Cortisol, matrix metalloproteinase 3, and urinary C-telopeptide of type II collagen were not significantly different between groups. More minor adverse events were noted in the spironolactone group (47 versus 32), but no increase in death or hospitalization was evident. Conclusion: Spironolactone did not improve symptoms, physical function, or health-related quality of life in older people with knee OA

Acceptability and feasibility of magnetic femoral nerve stimulation in older, functionally impaired patients

Abstract Objective Magnetic femoral nerve stimulation to test muscle function has been largely unexplored in older people. We assessed acceptability, feasibility, along with reproducibility and correlation with other physical function measures. Results Study 1 recruited older people with sarcopenia. Stimulation was performed at baseline and 2 weeks along with six minute walk (6MW), maximum voluntary quadriceps contraction, short physical performance battery and grip strength. Acceptability was measured using visual analog scales. Study 2 used baseline data from a trial of older people. We correlated stimulation results with 6MW, maximal voluntary contraction and muscle mass. Maximum quadriceps twitch tension was measured in both studies, evoked using biphasic magnetic stimulation of the femoral nerve. In study 1 (n = 12), magnetic stimulation was well tolerated with mean discomfort rating of 9% (range 0–40%) on a visual analog scale. Reproducibility was poor (intraclass correlation coefficient 0.06; p = 0.44). Study 2 (n = 64) showed only weak to moderate correlations for maximum quadriceps twitch tension with other measures of physical function (6 minute walk test r = 0.24, p = 0.06; maximal voluntary contraction r = 0.26; p = 0.04). We conclude that magnetic femoral nerve stimulation is acceptable and feasible but poorly reproducible in older, functionally impaired people

Association between mitochondrial function measured by 31P Magnetic Resonance Spectroscopy and physical performance in older people with functional impairment

Abstract Background Mitochondrial dysfunction is a potential therapeutic target to improve skeletal muscle function, but the contribution of mitochondrial dysfunction to impaired skeletal muscle performance in older people remains unclear. The aim of this analysis was to test the association between measures of skeletal muscle mitochondrial function and physical performance in older people. Methods We analysed data from the Allopurinol in Functional Impairment trial. Participants aged 65 and over, who were unable to walk 400 m in 6 min, underwent 31P magnetic resonance spectroscopy of the calf after exercise at baseline and at 20 weeks follow up. The phosphocreatine recovery half‐life time (t1/2) was derived as a measure of mitochondrial function. Participants undertook the 6‐min walk test and the Short Physical Performance Battery. Muscle mass measured using the Akern 101 bio‐impedance analysis system. Bivariate correlations and multivariable regression analyses were conducted to determine associations between t1/2 and baseline factors. Results One hundred and seventeen participants underwent baseline 31P magnetic resonance spectroscopy, mean age 80.4 years (SD 6.0); 56 (48%) were female. Mean 6‐min walk was 291 m (SD 80), mean SPPB score was 8.4 (SD 1.9); t1/2 correlated significantly with Short Physical Performance Battery score (r = 0.22, P = 0.02) but not with 6‐min walk distance (r = 0.10, P = 0.29). In multivariable linear regression, muscle mass and total body weight, but not t1/2, were independently associated with Short Physical Performance Battery score and with 6‐min walk distance. Change in t1/2 was not significantly associated with change in Short Physical Performance Battery score (r = 0.03, P = 0.79) or with change in 6‐min walk distance (r = −0.11, P = 0.28). Conclusions Muscle mass, but not phosphocreatine recovery time, was consistently associated with Short Physical Performance Battery score and 6‐min walk distance in older people with functional impairment

Leucine and perindopril to improve physical performance in people over 70 years with sarcopenia : the LACE factorial RCT

Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health and Care Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 9, No. 8. See the NIHR Journals Library website for further project information.Peer reviewedPublisher PD

Recruitment strategies for sarcopenia trials – lessons from the LACE randomised controlled trial

Background: Sarcopenia is rarely diagnosed and is not recorded electronically in routine clinical care, posing challenges to trial recruitment. We describe the performance of four components of a strategy to efficiently recruit participants with sarcopenia to a trial of perindopril and/or leucine for sarcopenia: primary care vs. hospital recruitment, a comparison of central vs. local telephone pre-screening, performance of a questionnaire on physical function conducted as part of the pre-screening telephone call, and performance of bioimpedance measurement to identify low muscle mass. Methods: Hospital-based recruitment took place through inpatient and outpatient geriatric medicine services. Local research nurses reviewed medical notes and approached potentially eligible patients. Primary care recruitment reviewed primary care lists from collaborating practices, sending mailshots to patients aged 70 and over who were not taking angiotensin-converting enzyme inhibitors. Telephone pre-screening was conducted either by research nurses at each site or centrally by Tayside Clinical Trials Unit. The 10-point SARC-F questionnaire was used for pre-screening. De-identified recruitment information was held on a central electronic tracking system and analysed using SPSS. Bioimpedance was measured using the Akern BIA 101 system, with the Sergi equation used to estimate lean mass. Results: Fourteen UK sites recruited to the trial. The 1202 sets of notes in hospital-based care were reviewed at these sites; 7 participants (0.6% of total notes screened) were randomized. From primary care, 13 808 invitations were sent; 138 (1.0% of total invited) were randomized. 633/2987 primary care respondents were pre-screened centrally; the mean number of calls per respondent was 2.3. For 10 sites where central and local pre-screening could be compared, the conversion rate from pre-screening to randomization was 18/588 (3.1%) for centralized calls, compared with 73/1814 (4.0%) for local pre-screening calls (P = 0.29). A weak relationship was seen between higher (worse) SARC-F score at screening and lower likelihood of progression to randomization (r = −0.08, P = 0.03). Muscle mass estimates generated using the Sergi equation were systematically biased, and a recalibrated equation for bioimpedance-estimated muscle mass was derived. Conclusions: Primary care recruitment led to higher response rates and overall numbers randomized than hospital-based recruitment. Centralized pre-screening saved local research nurses' time but did not improve conversion to randomization. SARC-F did not help to target screening activity in this sarcopenia trial, and a recalibration of the equation for estimating muscle mass from bioimpedance measures may improve accuracy of the screening process