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 (\u3e80%), moderate agreement (70-80%) and low agreement (\u3c70%). 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 \u27general aspects of sarcopenia\u27 (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on \u27components of sarcopenia\u27 (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 \u27outcomes of sarcopenia\u27 (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 \u27components of sarcopenia\u27, whereas impaired physical performance was accepted as an \u27outcome\u27 rather than a \u27component\u27 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

Evidence of sound production by spawning lake trout (Salvelinus namaycush) in lakes Huron and Champlain

Two sounds associated with spawning lake trout (Salvelinus namaycush) in lakes Huron and Champlain were characterized by comparing sound recordings with behavioral data collected using acoustic telemetry and video. These sounds were named “growls” and “snaps” and were heard on lake trout spawning reefs, but not on a nonspawning reef, and were more common at night than during the day. Growls also occurred more often during the spawning period than the prespawning period, while the trend for snaps was reversed. In a laboratory flume, sounds occurred when male lake trout were displaying spawning behaviors: growls when males were quivering and parallel swimming and snaps when males moved their jaw. Combining our results with the observation of possible sound production by spawning splake (Salvelinus fontinalis × Salvelinus namaycush hybrid) provides rare evidence for spawning-related sound production by a salmonid or any other fish in the superorder Protacanthopterygii. Further characterization of these sounds could be useful for lake trout assessment, restoration, and control

Spinodal Decomposition in a Binary Polymer Mixture: Dynamic Self Consistent Field Theory and Monte Carlo Simulations

We investigate how the dynamics of a single chain influences the kinetics of early stage phase separation in a symmetric binary polymer mixture. We consider quenches from the disordered phase into the region of spinodal instability. On a mean field level we approach this problem with two methods: a dynamical extension of the self consistent field theory for Gaussian chains, with the density variables evolving in time, and the method of the external potential dynamics where the effective external fields are propagated in time. Different wave vector dependencies of the kinetic coefficient are taken into account. These early stages of spinodal decomposition are also studied through Monte Carlo simulations employing the bond fluctuation model that maps the chains -- in our case with 64 effective segments -- on a coarse grained lattice. The results obtained through self consistent field calculations and Monte Carlo simulations can be compared because the time, length, and temperature scales are mapped onto each other through the diffusion constant, the chain extension, and the energy of mixing. The quantitative comparison of the relaxation rate of the global structure factor shows that a kinetic coefficient according to the Rouse model gives a much better agreement than a local, i.e. wave vector independent, kinetic factor. Including fluctuations in the self consistent field calculations leads to a shorter time span of spinodal behaviour and a reduction of the relaxation rate for smaller wave vectors and prevents the relaxation rate from becoming negative for larger values of the wave vector. This is also in agreement with the simulation results.Comment: Phys.Rev.E in prin

Patient active time during therapy sessions in postacute rehabilitation: Development and validation of a new measure

BACKGROUND AND PURPOSE: The accurate measurement of therapy intensity in postacute rehabilitation is important for research to improve outcomes in this setting. We developed and validated a measure of Patient Active Time during physical (PT) and occupational therapy (OT) sessions, as a proxy for therapy intensity. METHODS: This measurement validity study was carried out with 26 older adults admitted to a skilled nursing facility (SNF) for postacute rehabilitation with a variety of main underlying diagnoses, including hip fracture, cardiovascular diseases, stroke, and others. They were participants in a randomized controlled trial that compared an experimental high-intensity therapy to standard-of-care therapy. Patient Active Time was observed by research raters as the total number of minutes that a patient was actively engaging in therapeutic activities during PT and OT sessions. This was compared to patient movement (actigraphy) quantified during some of the same PT/OT sessions using data from three-dimensional accelerometers worn on the patient’s extremities. RESULTS: Activity measures were collected for 136 therapy sessions. Patient Active Time had high interrater reliability in both PT (r = 0.995, p < 0.001) and OT (r = 0.95, p = 0.012). Active time was significantly correlated with actigraphy in both PT (r = 0.73, p < 0.001) and OT (r = 0.60, p < 0.001) and discriminated between a high-intensity experimental condition and standard of care rehabilitation: in PT, 47.0 ± 13.5 min versus 16.7 ± 10.1 min (p < 0.001) and in OT, 46.2 ± 15.2 versus 27.7 ± 6.6 min (p < 0.001). CONCLUSIONS: Systematic observation of Patient Active Time provides an objective, reliable, and valid index of physical activity during PT and OT treatment sessions that has utility as a real-world alternative to the measurement of treatment intensity. This measure could be used to differentiate higher from lower therapy treatment intensity and to help determine the optimal level of active therapy time for patients in postacute and other settings

Effect of enhanced medical rehabilitation on functional recovery in older adults receiving skilled nursing care after acute rehabilitation: A randomized clinical trial

Importance: Enhanced medical rehabilitation (EMR) is a systematic and standardized approach for physical and occupational therapists to engage patients. Higher patient engagement in therapy might lead to improved functional recovery in rehabilitation settings, such as skilled nursing facilities (SNFs). Objective: To determine whether EMR improves older adults\u27 functional recovery. Design, Setting, and Participants: A double-blind, parallel-group, randomized clinical trial was conducted from July 29, 2014, to July 13, 2018, in 229 adults aged 65 years or older admitted to 2 US SNFs. Participants were randomized to receive EMR (n = 114) vs standard-of-care rehabilitation (n = 115). Intention-to-treat analysis was used. Interventions: The intervention group received their physical and occupational therapy from therapists trained in EMR. Based on models of motivation and behavior change, EMR is a toolkit of techniques to increase patient engagement and therapy intensity. The control group received standard-of-care rehabilitation from physical and occupational therapists not trained in EMR. Main Outcomes and Measures: The primary outcome was change in function in activities of daily living and mobility, as assessed with the Barthel Index, which measures 10 basic activities of daily living or mobility items (scale range, 0-100), from SNF admission to discharge; secondary outcomes were gait speed for 10 m, 6-minute walk test, discharge disposition, rehospitalizations, and self-reported functional status at days 30, 60, and 90. To examine the rehabilitation process, therapists\u27 engagement with patients and patient active time during therapy were measured for a sample of the sessions. Results: Of the 229 participants, 149 (65.1%) were women; 177 (77.3%) were white, and 51 (22.3%) were black; mean (SD) age was 79.3 (8.0) years. Participants assigned to EMR showed greater recovery of function than those assigned to standard of care (mean increase in Barthel Index score, 35 points; 95% CI, 31.6-38.3 vs 28 points; 95% CI, 25.2-31.7 points; P = .007). There was no evidence of a difference in the length of stay (mean [SD], 23.5 [13.1] days). However, there were no group by time differences in secondary outcome measures, including self-reported function after SNF discharge out to 90 days as measured on the Barthel Index (mean [SE] score: EMR, 83.65 [2.20]; standard of care, 84.67 [2.16]; P = .96). The EMR therapists used a median (interquartile range) of 24.4 (21.0-37.3) motivational messages per therapy session vs 2.3 (1.1-2.9) for nontrained therapists (P \u3c .001), and EMR patients were active during a mean (SD) of 52.5 (6.6%) of the therapy session time vs 41.2 (6.8%) for nontrained therapists (P = .001). Conclusions and Relevance: Enhanced medical rehabilitation modestly improved short-term functional recovery for selected older adults rehabilitating in SNFs. However, there was no evidence that the benefits persisted over the longer term. This study demonstrates the value of engaging and motivating older adults in rehabilitation therapy, but more work is needed to extend these benefits to longer-term outcomes after discharge home. Trial Registration: ClinicalTrials.gov identifier: NCT02114879

Evaluation of noise regression techniques in resting-state fMRI studies using data of 434 older adults

Subject motion is a well-known confound in resting-state functional MRI (rs-fMRI) and the analysis of functional connectivity. Consequently, several clean-up strategies have been established to minimize the impact of subject motion. Physiological signals in response to cardiac activity and respiration are also known to alter the apparent rs-fMRI connectivity. Comprehensive comparisons of common noise regression techniques showed that the Independent Component Analysis based strategy for Automatic Removal of Motion Artifacts (ICA-AROMA) was a preferred pre-processing technique for teenagers and adults. However, motion and physiological noise characteristics may differ substantially for older adults. Here, we present a comprehensive comparison of noise-regression techniques for older adults from a large multi-site clinical trial of exercise and intensive pharmacological vascular risk factor reduction. The Risk Reduction for Alzheimer\u27s Disease (rrAD) trial included hypertensive older adults (60-84 years old) at elevated risk of developing Alzheimer\u27s Disease (AD). We compared the performance of censoring, censoring combined with global signal regression, non-aggressive and aggressive ICA-AROMA, as well as the Spatially Organized Component Klassifikator (SOCK) on the rs-fMRI baseline scans from 434 rrAD subjects. All techniques were rated based on network reproducibility, network identifiability, edge activity, spatial smoothness, and loss of temporal degrees of freedom (tDOF). We found that non-aggressive ICA-AROMA did not perform as well as the other four techniques, which performed table with marginal differences, demonstrating the validity of these techniques. Considering reproducibility as the most important factor for longitudinal studies, given low false-positive rates and a better preserved, more cohesive temporal structure, currently aggressive ICA-AROMA is likely the most suitable noise regression technique for rs-fMRI studies of older adults

Rationale and Methods for a Multicenter Clinical Trial Assessing Exercise and Intensive Vascular Risk Reduction in Preventing Dementia (rrAD Study)

Alzheimer\u27s Disease (AD) is an age-related disease with modifiable risk factors such as hypertension, hypercholesterolemia, obesity, and physical inactivity influencing the onset and progression. There is however, no direct evidence that reducing these risk factors prevents or slows AD. The Risk Reduction for Alzheimer\u27s Disease (rrAD) trial is designed to study the independent and combined effects of intensive pharmacological control of blood pressure and cholesterol and exercise training on neurocognitive function. Six hundred and forty cognitively normal older adults age 60 to 85 years with hypertension and increased risk for dementia will be enrolled. Participants are randomized into one of four intervention group for two years: usual care, Intensive Reduction of Vascular Risk factors (IRVR) with blood pressure and cholesterol reduction, exercise training (EX), and IRVR+EX. Neurocognitive function is measured at baseline, 6, 12, 18, and 24 months; brain MRIs are obtained at baseline and 24 months. We hypothesize that both IRVR and EX will improve global cognitive function, while IRVR+EX will provide a greater benefit than either IRVR or EX alone. We also hypothesize that IRVR and EX will slow brain atrophy, improve brain structural and functional connectivity, and improve brain perfusion. Finally, we will explore the mechanisms by which study interventions impact neurocognition and brain. If rrAD interventions are shown to be safe, practical, and successful, our study will have a significant impact on reducing the risks of AD in older adults. NCT Registration: NCT02913664

Association of functional polymorphisms from brain-derived neurotrophic factor and serotonin-related genes with depressive symptoms after a medical stressor in older adults

Depressive symptoms are common in older adults after a disabling medical event and interfere with rehabilitation and recovery from the disability. This prospective study examined the role of genetic polymorphisms implicated in synaptic integrity and stress-associated depression as predictors of depressive symptoms after hip fracture. We recruited healthy comparisons from the community and participants with hip fracture after surgical fixation from Saint Louis, Missouri hospitals. We examined the valine (Val) to methionine (Met) polymorphism in brain-derived neurotrophic factor (BDNF), serotonin 1A receptor (5HT1a-rs6295) polymorphism, and the serotonin transporter-linked polymorphic region (5HTTLPR) interaction with the rs25531 A to G single nucleotide polymorphism (5HTTLPR-rs25531) as predictors of depressive symptoms. We also examined whether depressive symptoms mediate the influence of BDNF genotype on functional recovery. Among 429 participants with hip fracture, BDNF Met/Met carriers developed significantly more depressive symptoms than Val/Val carriers during a four-week period after the fracture (p=.012). BDNF genotype also predicted functional recovery over the ensuing year, mediated by its effects on depressive symptoms (CI: 0.07-3.37). Unlike prior studies of stressful life events, the S' 5HTTLPR-rs25531 variant did not predict higher levels of depressive symptoms; instead, we report an exploratory finding of an epistatic effect between BDNF and 5HTTLPR-rs25531 whereby the compounded effects of two LA alleles and BDNF Met/Met genotype elevate risk of depressive symptoms after hip fracture (p=.006). No differences between 5HT1a genotypes were found. Our findings suggest plasticity-related genetic factors contribute to the neural mechanisms of mental and functional well-being after a disabling medical stressor

Enteric Neurospheres Are Not Specific to Neural Crest Cultures: Implications for Neural Stem Cell Therapies

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