The Conceptual Definition of Sarcopenia: Delphi Consensus from the Global Leadership Initiative in Sarcopenia (GLIS).

IMPORTANCE: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. OBJECTIVE: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. DESIGN: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (>80%), moderate agreement (70-80%) and low agreement (<70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. RESULTS: 107 participants (mean age: 54 ± 12 years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on 'general aspects of sarcopenia' (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on 'components of sarcopenia' (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on 'outcomes of sarcopenia' (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as 'components of sarcopenia', whereas impaired physical performance was accepted as an 'outcome' rather than a 'component' of sarcopenia. CONCLUSION AND RELEVANCE: The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings.

Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts.

BACKGROUND: Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited. AIM: We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors. METHODS: Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index). RESULTS: Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed. CONCLUSIONS: Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskeletal Conditions and Aging.

In clinical trials, biochemical markers provide useful information on the drug's mode of action, therapeutic response and side effect monitoring and can act as surrogate endpoints. In pharmacological intervention development for sarcopenia management, there is an urgent need to identify biomarkers to measure in clinical trials and that could be used in the future in clinical practice. The objective of the current consensus paper is to provide a clear list of biochemical markers of musculoskeletal health and aging that can be recommended to be measured in Phase II and Phase III clinical trials evaluating new chemical entities for sarcopenia treatment. A working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) proposed classifying biochemical markers into 2 series: biochemical markers evaluating musculoskeletal status and biochemical markers evaluating causal factors. For series 1, the group agreed on 4 biochemical markers that should be assessed in Phase II or Phase III trials (i.e., Myostatin-Follistatin, Brain Derived Neurotrophic Factor, N-terminal Type III Procollagen and Serum Creatinine to Serum Cystatin C Ratio - or the Sarcopenia Index). For series 2, the group agreed on 6 biochemical markers that should be assessed in Phase II trials (i.e., the hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate, and cortisol, and the inflammatory markers C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-α), and 2 in Phase III trials (i.e., IGF-I and CRP). The group also proposed optional biochemical markers that may provide insights into the mode of action of pharmacological therapies. Further research and development of new methods for biochemical marker assays may lead to the evolution of these recommendations.

Frailty and anticoagulants in older subjects with atrial fibrillation: the EUROSAF study.

AIMS: Literature regarding anticoagulants in older people affected by atrial fibrillation (AF) is limited to retrospective studies, poorly considering the importance of multidimensional frailty. The main objective of this study is to evaluate in hospitalised older persons with AF the benefit/risk ratio of the anticoagulant treatments, considering the severity of frailty, determined by the multidimensional prognostic index (MPI). METHODS: In this European, multicentre, prospective study, older hospitalised patients (≥65 years) with non-valvular AF were followed-up for 12 months. Anticoagulants' use at discharge ascertained using medical records. MPI was calculated using tools derived from comprehensive geriatric assessment, classifying participants in robust, pre-frail or frail. Mortality (primary outcome); vascular events, including ischemic heart disease or ischemic stroke, hemorrhagic stroke or gastrointestinal bleedings (secondary outcomes). RESULTS: 2,022 participants (mean age 82.9 years; females 56.6%) were included. Compared with people not taking anticoagulants (n = 823), people using vitamin K antagonists (n = 450) showed a decreased risk of mortality (hazard ratio, HR = 0.74; 95% CI: 0.59-0.93), more pronounced in patients using direct oral anticoagulants (DOACs) (n = 749) (HR = 0.46; 95% CI: 0.37-0.57). Only people taking DOACs reported a significantly lower risk of vascular events (HR = 0.55; 95% CI: 0.31-0.97). The efficacy of DOACs was present independently from frailty status. The risk of gastrointestinal bleedings and hemorrhagic stroke did not differ based on the anticoagulant treatments and by MPI values. CONCLUSIONS: Anticoagulant treatment, particularly with DOACs, was associated with reduced mortality in older people, without increasing the risk of hemorrhagic events, overall suggesting the importance of treating with anticoagulants older people with AF.

Acute Sarcopenia.

Sarcopenia is currently understood as an organ insufficiency. However, the distinction of acute and chronic sarcopenia as different categories, which makes sense in this conceptual framework, is still evolving. The first set of modern definitions of sarcopenia only considered chronic sarcopenia. However, research showed that function in acute care settings differs from the loss that evolves slowly over months or years, and this fact is starting to permeate modern definitions. The updated version of the EWGSOP definition identifies acute and chronic sarcopenia as subcategories. Different studies have reported rates of incident sarcopenia in hospitalised older patients around 15-20%, which adds to the prevalent sarcopenia present on admission. Diagnosing sarcopenia in acute settings carries specific challenges related to the patients, the acute condition, and limitations in the use of diagnostic tests for muscle mass, muscle strength, and physical performance. Prevention and management of acute sarcopenia rely on exercise during admission, but the quality of evidence is still low. Nutritional intervention and drugs may have a role, but more research is needed.

A Core Outcome Set for nutritional intervention studies in older adults with malnutrition and those at risk: a study protocol.

BACKGROUND: Malnutrition (i.e., protein-energy malnutrition) in older adults has severe negative clinical consequences, emphasizing the need for effective treatments. Many, often small, randomized controlled trials (RCTs) testing the effectiveness of nutritional interventions for the treatment of malnutrition showed mixed results and a need for meta-analyses and data pooling has been expressed. However, evidence synthesis is hampered by the wide variety of outcomes and their method of assessment in previous RCTs. This paper describes the protocol for developing a Core Outcome Set (COS) for nutritional intervention studies in older adults with malnutrition and those at risk. METHODS: The project consists of five phases. The first phase consists of a scoping review to identify frequently used outcomes in published RCTs and select additional patient-reported outcomes. The second phase includes a modified Delphi Survey involving experienced researchers and health care professionals working in the field of malnutrition in older adults, followed by the third phase consisting of a consensus meeting to discuss and agree what critical outcomes need to be included in the COS. The fourth phase will determine how each COS outcome should be measured based on a systematic literature review and a second consensus meeting. This will be followed by a dissemination and implementation phase. Patient and Public Involvement (PPI) representatives will contribute to study design, oversight, consensus, and dissemination. CONCLUSIONS: The result of this project is a COS that should be included in any RCT evaluating the effect of nutritional interventions in older adults with malnutrition and those at risk. This COS will facilitate comparison of RCT results, will increase efficient use of research resources and will reduce bias due to measurement of the outcome and publication bias. Ultimately, the COS will support clinical decision making by identifying the most effective approaches for treating and preventing malnutrition in older adults.

Association of periodontitis with handgrip strength and skeletal muscle mass in middle-aged US adults from NHANES 2013-2014.

OBJECTIVES: The relationship between periodontitis and sarcopenia parameters in middle-aged adults is largely unexplored. This study investigated the association between periodontitis and combined handgrip strength and skeletal muscle mass in middle-aged adults. MATERIALS AND METHODS: A sub-cohort of 1912 individuals with complete periodontal and whole-body dual X-ray absorptiometry examinations from the 2013-2014 wave of the National Health and Nutrition Examination Survey (n = 10,175) were analyzed using fully adjusted multiple linear regression models for associations between periodontitis and skeletal muscle mass index (kg/m2) and combined handgrip strength (kg). RESULTS: The mean age of the study cohort was 43 (± 8.4) years and 49.4% of the participants were male. In total, 612 participants (32%) were determined to have periodontitis, of which 513 (26.8%) had non-severe (mild or moderate) periodontitis, and 99 (5.2%) had severe periodontitis. In unadjusted regression models, both non-severe and severe periodontitis were associated with SMMI (ßnon-severe = 1.01, 95% CI 0.50; 1.52 and ßsevere = 1.42, 95% CI 0.59; 2.25) but not with cHGS. After adjusting for age, sex, education, body mass index, bone mineral density, diabetic status, education, total energy intake, total protein intake, and serum vitamin D2 + D3, periodontitis was associated with cHGS (ßnon-severe = -2.81, 95% CI - 4.7; - 1.15 and ßsevere = - 2.73, 95% CI - 6.31; 0.83). The association between periodontitis and SMMI remained for non-severe periodontitis (ßnon-severe = 0.07, 95% CI - 0.26; 0.40 and ßsevere = 0.22, 95% CI - 0.34; 0.78). CONCLUSION: The present study highlights the need of further prospective research to investigate the nature and direction of the relationship between periodontitis and sarcopenia indicators. Future studies can support the screening, prevention and clinical management of sarcopenia and periodontitis, and emphasize the interdisciplinary and complementary approach between the disciplines of geriatric medicine and periodontology.

Measuring health-related quality of life in sarcopenia: summary of the SarQoL psychometric properties.

Patient perspectives are now widely recognized as a key element in the evaluation of health interventions. Therefore, the provision of specific and validated Patient Reported Outcome Measures that emphasize the lived experience of patients suffering from specific diseases is very important. In the field of sarcopenia, the only validated specific health-related quality of life (HRQoL) instrument available is the Sarcopenia Quality of Life questionnaire (SarQoL). This self-administrated HRQoL questionnaire, developed in 2015, consists of 55 items arranged into 22 questions and has currently been translated into 35 languages. Nineteen validation studies performed on SarQoL have consensually confirmed the capacity of SarQoL to detect difference in HRQoL between older people with and without sarcopenia, its reliability and its validity. Two further observational studies have also indicated its responsiveness to change. A short form SarQoL, including only 14 items has further been developed and validated to reduce the potential burden of administration. Research on the psychometric properties of SarQoL questionnaire is still encouraged as the responsiveness to change of SarQoL has not yet been measured in the context of interventional studies, as limited prospective data currently exist and as there is still not cut-off score to define a low HRQoL. In addition, SarQoL has mainly been used in community-dwelling older individuals with sarcopenia and would benefit to be studied in other types of populations. This review aims to provide to researchers, clinicians, regulators, pharmaceutical industries and other stakeholders a clear summary of comprehensive evidence on the SarQoL questionnaire published up to January 2023Query.

Role of vitamin D supplementation in the management of musculoskeletal diseases: update from an European Society of Clinical and Economical Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group.

Vitamin D is a key component for optimal growth and for calcium-phosphate homeostasis. Skin photosynthesis is the main source of vitamin D. Limited sun exposure and insufficient dietary vitamin D supply justify vitamin D supplementation in certain age groups. In older adults, recommended doses for vitamin D supplementation vary between 200 and 2000 IU/day, to achieve a goal of circulating 25-hydroxyvitamin D (calcifediol) of at least 50 nmol/L. The target level depends on the population being supplemented, the assessed system, and the outcome. Several recent large randomized trials with oral vitamin D regimens varying between 2000 and 100,000 IU/month and mostly conducted in vitamin D-replete and healthy individuals have failed to detect any efficacy of these approaches for the prevention of fracture and falls. Considering the well-recognized major musculoskeletal disorders associated with severe vitamin D deficiency and taking into account a possible biphasic effects of vitamin D on fracture and fall risks, an European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group convened, carefully reviewed, and analyzed the meta-analyses of randomized controlled trials on the effects of vitamin D on fracture risk, falls or osteoarthritis, and came to the conclusion that 1000 IU daily should be recommended in patients at increased risk of vitamin D deficiency. The group also addressed the identification of patients possibly benefitting from a vitamin D loading dose to achieve early 25-hydroxyvitamin D therapeutic level or from calcifediol administration.

Spanish translation, cultural adaptation and validation of the SarQoL®: a specific health-related quality of life questionnaire for sarcopenia.

BACKGROUND: In 2015, a specific health-related quality of life questionnaire for sarcopenia, SarQoL®, was developed and validated in French. Since then, SarQoL® has been adapted and validated in different languages. We prepared a translation, cultural adaptation and validation of the psychometric properties of the SarQoL® into Spanish. METHODS: A cross-sectional study with 86 participants. The translation and adaptation followed international guidelines with two direct translations, a synthesized version of the direct translations, two reverse translations, consensus by an expert committee of a pre-final version, pre-test by end users and final version. The discriminative power (logistic regression analyses), construct validity (Pearson and Spearman´s correlation), internal consistency (Cronbach´s alpha coefficient), test-retest reliability (intraclass correlation coefficient) and ceiling and floor effects were analyzed. RESULTS: The Spanish version showed good construct validity (high correlation with comparable domains of the SF-36), high internal consistency (Cronbach's alpha coefficient: 0.84) and excellent test-retest reliability (ICC: 0.967, 95%, CI 0.917 - 0.989). However, it had no discriminative power between sarcopenic and non-sarcopenic participants defined with the EWGSOP and FNIH diagnostic criteria of sarcopenia. It did show discriminative power between patients with decreased vs normal muscle strength (54.9 vs. 62.6, p 0.009) and low vs. normal physical performance (57.3 vs. 70.2; p 0.005). No ceiling or floor effect was found. CONCLUSIONS: The Spanish version of SarQoL® has similar psychometric properties to those of the original version of the instrument. It did not discriminate between sarcopenic and non-sarcopenic patients diagnosed according to the EWGSOP or FNIH criteria, but it did with those with low muscle strength and low physical performance.

ß-hydroxy-ß-methylbutyrate supplementation in older persons - an update.

PURPOSE OF REVIEW: The interest in the use of beta-hydroxy-beta-methylbutyrate (HMB) as an intervention to prevent and treat sarcopenia has increased over recent years. The purpose of this review is to explore recent evidence pertaining to the mechanism of action of HMB and how this may influence changes in lean mass and strength in older persons who are both hospitalized and living in the community. RECENT FINDINGS: No new studies have been published over the last 2 years investigating the effect of HMB in older persons who are hospitalized, aside from one posthoc analysis of a randomized controlled trial exploring the effect of a high protein oral nutrition supplement containing HMB on handgrip strength and nutritional status. Three studies recruiting community-dwelling older adults have been published, but results are influenced by suboptimal methodological quality. SUMMARY: Recent data suggest the need for high-quality studies investigating the effectiveness of HMB to improve outcomes related to sarcopenia in both hospitalized and community-dwelling older persons.

Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials.

BACKGROUND: Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in older people with clinically manifest frailty. METHODS: A literature search was performed in Medline to detect prospective randomized controlled trials (RCTs) testing the effects of pharmacological interventions or medication optimization in older frail adults on comprehensive frailty scores or partial aspects of frailty that were published from January 1998 to October 2019. RESULTS: Twenty-five studies were identified, 4 on comprehensive frailty scores and 21 on aspects of frailty. Two trials on comprehensive frailty scores showed positive results on frailty although the contribution of medication review in a multidimensional approach was unclear. In the studies on aspects related to frailty, ten individual drug interventions showed improvement in physical performance, muscle strength or body composition utilizing alfacalcidol, teriparatide, piroxicam, testosterone, recombinant human chorionic gonadotropin, or capromorelin. There were no studies examining negative effects of drugs on frailty. CONCLUSION: So far, data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions on partial aspects of frailty. There is a clear need for RCTs on this topic that should be based on a comprehensive, internationally consistent and thus reproducible concept of frailty assessment.

Oropharyngeal dysphagia in older patients with hip fracture.

BACKGROUND: oropharyngeal dysphagia (OD) and hip fracture are common problems in older patients, both associated with important complications. OBJECTIVE: the aim of this study was to measure the prevalence and identify the main risk factors of dysphagia in older patients with hip fracture. DESIGN: a prospective study in an orthogeriatric unit of a university hospital over 10 months. METHODS: a total of 320 patients (mean age 86.2 years, 73.4% women) were assessed for dysphagia within 72 hours post-surgery using the Volume-Viscosity Swallow Test. Geriatric assessment, hip fracture management and complications were examined to determine their relationship with the presence of OD. RESULTS: dysphagia was present in 176 (55%) patients. Multivariate logistic regression analysis showed that the presence of delirium during hospitalization and the inability to perform instrumental activities of daily living before admission were associated with OD. CONCLUSIONS: the prevalence of OD is high in hip fracture patients. Objective dysphagia assessment should be routinely included as part of the geriatric assessment of such patients.

Sarcopenia, immune-mediated rheumatic diseases, and nutritional interventions.

INTRODUCTION: Sarcopenia is defined by a loss of muscle mass and function associated with mortality, decreased physical performance, falls, and disability. Since chronic inflammation and decreased physical activity are risk factors for developing sarcopenia, it is critical to assess the role of sarcopenia in immune-mediated rheumatic diseases (IMRDs). Moreover, nutritional interventions are emerging as key modifiable and affordable options to improve physical performance in sarcopenia. OBJECTIVE: The aim of this review is to critically summarize current information on the evidence linking nutritional interventions and sarcopenia in IMRDs. METHODS: The search and selection of articles was performed in Medline, Dimensions.ai, Google Scholar, Cochrane Library, Epistemonikos, and Trip Database. The results were clustered into three areas: sarcopenia and IMRDs, sarcopenia and biological disease-modifying antirheumatic drugs (bDMARDs), and nutritional interventions for sarcopenia. FINDINGS: Several cross-sectional studies have shown a higher prevalence of sarcopenia in IMRDs, such as rheumatoid arthritis. Although not fully established, evidence linking sarcopenia and other IMRDs (ankylosing spondylitis and systemic sclerosis) has been also described. For secondary sarcopenia prevention and treatment, bDMARDs' administration proved efficacy in patients with rheumatoid arthritis. Furthermore, there is growing evidence linking nutrition to the prevention and treatment of sarcopenia. Evidence linking unfavourable results in nutritional risk assessment, insufficient intake of protein, vitamin D, antioxidant nutrients, and long-chain polyunsaturated fatty acids and sarcopenia have been reported. CONCLUSION: Given that sarcopenia and IMRDs have strong links, further research is needed to improve patient care.

Muscle strength cutoff values calculated from the young reference population to evaluate sarcopenia in Turkish population.

Sarcopenia is defined as a progressive and generalized skeletal muscle disorder that is associated with an increased likelihood of adverse outcomes, including mobility problems and mortality. To reach a global consensus for its standard definition and diagnosis, more recently, a revised EWGSOP consensus (EWGSOP2) has been published. In EWGSOP2 definition, sarcopenia has been regarded as skeletal muscle failure and low muscle strength has been put forward as its key defining characteristics. EWGSOP2 suggested the use of handgrip strength cutoff values calculated by mean minus 2.5 standard deviations of the young healthy population. In this report, following EWGSOP2's suggestion, we aimed to outline the handgrip strength cutoffs derived from a young Turkish reference population, and compare them with the other population-specific reports.

Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults.

BACKGROUND: In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. AIMS: The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. METHODS: This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. RESULTS: The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. CONCLUSION: The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

The Antipsychotic Risperidone Alters Dihydroceramide and Ceramide Composition and Plasma Membrane Function in Leukocytes In Vitro and In Vivo.

Atypical or second-generation antipsychotics are used in the treatment of psychosis and behavioral problems in older persons with dementia. However, these pharmaceutical drugs are associated with an increased risk of stroke in such patients. In this study, we evaluated the effects of risperidone treatment on phospholipid and sphingolipid composition and lipid raft function in peripheral blood mononuclear cells (PBMCs) of older patients (mean age >88 years). The results showed that the levels of dihydroceramides, very-long-chain ceramides, and lysophosphatidylcholines decreased in PBMCs of the risperidone-treated group compared with untreated controls. These findings were confirmed by in vitro assays using human THP-1 monocytes. The reduction in the levels of very-long-chain ceramides and dihydroceramides could be due to the decrease in the expression of fatty acid elongase 3, as observed in THP-1 monocytes. Moreover, risperidone disrupted lipid raft domains in the plasma membrane of PBMCs. These results indicated that risperidone alters phospholipid and sphingolipid composition and lipid raft domains in PBMCs of older patients, potentially affecting multiple signaling pathways associated with these membrane domains.

Sarcopenia.

Sarcopenia is a progressive and generalised skeletal muscle disorder involving the accelerated loss of muscle mass and function that is associated with increased adverse outcomes including falls, functional decline, frailty, and mortality. It occurs commonly as an age-related process in older people, influenced not only by contemporaneous risk factors, but also by genetic and lifestyle factors operating across the life course. It can also occur in mid-life in association with a range of conditions. Sarcopenia has become the focus of intense research aiming to translate current knowledge about its pathophysiology into improved diagnosis and treatment, with particular interest in the development of biomarkers, nutritional interventions, and drugs to augment the beneficial effects of resistance exercise. Designing effective preventive strategies that people can apply during their lifetime is of primary concern. Diagnosis, treatment, and prevention of sarcopenia is likely to become part of routine clinical practice.

Defining sarcopenia: some caveats and challenges.

PURPOSE OF REVIEW: To summarize the latest advances and caveats in defining sarcopenia and discuss the implications of the most recent worldwide initiatives which are trying to harmonize the definition. RECENT FINDINGS: The evolution over time of the definitions of sarcopenia is discussed, with a focus on the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) definition and the Sarcopenia Definitions and Outcomes Consortium (SDOC) conference. The EWGSOP2 and the SDOC agree on the overall concept of sarcopenia, which involves both impaired function (low muscle strength) and structural damage (low muscle mass/quality). However, physical performance is considered as a diagnostic criterion (EWGSOP), a severity grading assessment (EWGSOP2) or an outcome (SDOC) pending on the definition used. Muscle strength has been recognized as the best predictor of health outcomes. Muscle mass alone, as part of the definition of cachexia, sarcopenia and malnutrition, is a nondefining parameter. Furthermore, there is a lack of precision in measurement techniques and variability of the cut-off points in defining it. SUMMARY: We discuss the relationship of sarcopenia with cachexia, malnutrition and frailty, and the areas that are hampering agreement. We summarize key scientific evidence, consider future study of this nutrition-related disease and raise concern about the need for a universal definition of sarcopenia.

Prevalence of sarcopenia and its components in community-dwelling outpatient older adults and their relation with functionality.

AIM: Sarcopenia is recognized with its adverse functional outcomes. We aimed to report the prevalence of European Working Group on Sarcopenia in Older People (EWGSOP) defined sarcopenia and its individual components in community dwelling outpatient older adults and study the correlations of EWGSOP defined sarcopenia, muscle mass, muscle strength, and physical performance with functional status. MATERIAL AND METHODS: The subjects were prospectively recruited from the geriatrics outpatient clinics of our university hospital. Body composition was assessed with bioimpedance analysis. Muscle strength was assessed by measurement of hand grip strength with hydraulic hand dynamometer, physical performance was assessed by 4 meter usual gait speed (UGS). Impaired muscle function was defined as presence of low muscle strength and or slow gait speed. As a measure of functionality, modified version of Katz activities of daily living (ADL) and Lawton instrumental activities of daily living (IADL) were assessed. RESULTS: A total of 242 community dwelling outpatients with mean age of 79.4 ± 5.7 years were enrolled. 31.8% were male. Prevalence of low muscle mass was 2.1% and impaired muscle function was 71.1%. Prevalence of EWGSOP defined sarcopenia was 0.8% (1.3% in men and 0.6% in women). Most correlated parameter with ADL and IADL was the usual gait speed (r = 0.49, r = 0.63; p < .001, respectively). Grip strength was also correlated with ADL and IADL (r = 0.28, r = 0.35; p < .001). However, the skeletal muscle mass index (SMMI) was not correlated with ADL, IADL (p = .22, p = .22, respectively). In regression analysis, both ADL score and IADL scores were most related to UGS (beta = 0.5 and 0.6, p < .001), age (beta = -0.25 and -0.2, p < .001) and then sarcopenia (beta = 0.1 and 0.1, p < .05) but was not related to hand grip strength or SMMI. CONCLUSIONS: The prevalence of sarcopenia was low as 0.8% albeit the presence of impaired muscle function in more than 2/3 of the cases. We have found that EWGSOP defined sarcopenia had association with ADL and IADL. The gait speed component of sarcopenia had the strongest associations with functional measures but SMMI component did not have any relation. We suggest that although low muscle mass may be a parameter related to worse functionality, it should not be regarded prerequisite for presence of sarcopenia analogous to low bone mineral density for osteoporosis.