Anorexia in Medicare Fee-for-Service Beneficiaries: A Claims-Based Analysis of Epidemiology and Mortality.

OBJECTIVES: Loss of appetite in older adults can lead to malnutrition, weight loss, frailty, and death, but little is known about its epidemiology in the United States (US). The objective of this study was to estimate the annual prevalence and incidence of anorexia in older adults with Medicare fee-for-service (FFS) health insurance. DESIGN: Retrospective and observational analysis of administrative health insurance claims data. SETTING: This study included Medicare FFS claims from all settings (eg, hospital inpatient/outpatient, office, assisted living facility, skilled nursing facility, hospice, rehabilitation facility, home). PARTICIPANTS: This study included all individuals aged 65 to 115 years old with continuous Medicare FFS medical coverage (Parts A and/or B) for at least one 12-month period from October 1, 2015, to September 30, 2021 (ie, approximately 30 million individuals each year). INTERVENTION: Not applicable. MEASUREMENTS: Anorexia was identified using medical claims with the ICD-10 diagnosis code "R63.0: Anorexia". This study compared individuals with anorexia to a control group without anorexia with respect to demographics, comorbidities using the Charlson Comorbidity Index (CCI), Claims-based Frailty Index (CFI), and annual mortality. The annual prevalence and incidence of anorexia were estimated for each 12-month period from October 1, 2015, to September 30, 2021. RESULTS: The number of individuals with anorexia ranged from 317,964 to 328,977 per year, a mean annual prevalence rate of 1.1%. The number of individuals newly diagnosed with anorexia ranged from 243,391 to 281,071 per year, a mean annual incidence rate of 0.9%. Individuals with anorexia had a mean (±standard deviation) age of 80.5±8.7 years (vs 74.9±7.5 years without anorexia; p<.001), 64.4% were female (vs 53.8%; p<.001), and 78.4% were White (vs 83.2%; p<.001). The most common CCI comorbidities for those with anorexia were chronic pulmonary disease (39.4%), dementia (38.3%), and peripheral vascular disease (38.0%). Median (interquartile range [IQR]) CCI with anorexia was 4 [5] (vs 1 [3] without anorexia; p<.001). The annual mortality rate among those with anorexia was 22.3% (vs 4.1% without anorexia; relative risk 5.49 [95% confidence interval, 5.45-5.53]). CONCLUSION: Approximately 1% of all adults aged 65-115 years old with Medicare FFS insurance are diagnosed with anorexia each year based on ICD-10 codes reported in claims. These individuals have a higher comorbidity burden and an increased risk of annual mortality compared to those without a diagnosis of anorexia. Further analyses are needed to better understand the relationship between anorexia, comorbidities, frailty, mortality, and other health outcomes.

Assessment and Management of Appetite Loss in Older Adults: An ICFSR Task Force Report.

The Appetite loss in older people is an important unmet clinical need in geriatrics. The International Conference on Frailty and Sarcopenia Research (ICFSR) organized a Task Force on April 20th 2022, in Boston, to discuss issues related to appetite loss in older people, in particular, the assessment tools currently available, its evaluation in the primary care setting, and considerations about its management. There is a high heterogeneity in terms of the etiology of appetite loss in older people and a gold standard assessment tool for evaluating this condition is still absent. Although this may render difficult the management of poor appetite in clinical practice, validated assessment tools are currently available to facilitate early identification of appetite loss and support care decisions. As research on biomarkers of appetite loss progresses, assessment tools will soon be used jointly with biomarkers for more accurate diagnosis and prognosis. In addition, efforts to foster the development of drugs with a favorable risk/benefit ratio to combat poor appetite should be strengthened.

Resilience: Biological Basis and Clinical Significance - A Perspective Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force.

The Resilience is a construct receiving growing attention from the scientific community in geriatrics and gerontology. Older adults show extremely heterogeneous (and often unpredictable) responses to stressors. Such heterogeneity can (at least partly) be explained by differences in resilience (i.e., the capacity of the organism to cope with stressors). The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met in Boston (MA,USA) on April 20, 2022 to discuss the biological and clinical significance of resilience in older adults. The identification of persons with low resilience and the prompt intervention in this at-risk population may be critical to develop and implement preventive strategies against adverse events. Unfortunately, to date, it is still challenging to capture resilience, especially due to its dynamic nature encompassing biological, clinical, subjective, and socioeconomic factors. Opportunities to dynamically measure resilience were discussed during the ICFSR Task Force meeting, emphasizing potential biomarkers and areas of intervention. This article reports the results of the meeting and may serve to support future actions in the field.

Appetite Loss and Anorexia of Aging in Clinical Care: An ICFSR Task Force Report.

Appetite loss/anorexia of aging is a highly prevalent and burdensome geriatric syndrome that strongly impairs the quality of life of older adults. Loss of appetite is associated with several clinical conditions, including comorbidities and other geriatric syndromes, such as frailty. Despite its importance, appetite loss has been under-evaluated and, consequently, under-diagnosed and under-treated in routine clinical care. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met virtually on September 27th 2021 to debate issues related to appetite loss/anorexia of aging. In particular, topics related to the implementation and management of appetite loss in at-risk older adult populations, energy balance during aging, and the design of future clinical trials on this topic were discussed. Future actions in this field should focus on the systematic assessment of appetite in the care pathway of older people, such as the Integrated Care for Older People (ICOPE) program recommended by the World Health Organization. Moreover, clinical care should move from the assessment to the treatment of appetite loss/anorexia. Researchers continue to pursue their efforts to find out effective pharmacologic and non-pharmacologic interventions with a favorable risk/benefit ratio.

Challenges in the Development of Drugs for Sarcopenia and Frailty - Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force.

Sarcopenia and frailty represent two burdensome conditions, contributing to a broad spectrum of adverse outcomes. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met virtually in September 2021 to discuss the challenges in the development of drugs for sarcopenia and frailty. Lifestyle interventions are the current mainstay of treatment options in the prevention and management of both conditions. However, pharmacological agents are needed for people who do not respond to lifestyle modifications, for those who are unable to adhere, or for whom such interventions are inaccessible/unfeasible. Preliminary results of ongoing trials were presented and discussed. Several pharmacological candidates are currently under clinical evaluation with promising early results, but none have been approved for either frailty or sarcopenia. The COVID-19 pandemic has reshaped how clinical trials are conducted, in particular by enhancing the usefulness of remote technologies and assessments/interventions.

Recommendations for Reducing Heterogeneity in Handgrip Strength Protocols.

Handgrip dynamometers are widely used to measure handgrip strength (HGS). HGS is a safe and easy to obtain measure of strength capacity, and a reliable assessment of muscle function. Although HGS provides robust prognostic value and utility, several protocol variants exist for HGS in clinical settings and translational research. This lack of methodological consistency could threaten the precision of HGS measurements and limit comparisons between the growing number of studies measuring HGS. Providing awareness of the protocol variants for HGS and making suggestions to reduce the implications of these variants will help to improve methodological consistency. Moreover, leveraging recent advancements in HGS equipment may enable us to use more sophisticated HGS dynamometer technologies to better assess muscle function. This Special Article will 1) highlight differences in HGS protocols and instrumentation, 2) provide recommendations to better specify HGS procedures and equipment, and 3) present future research directions for studies that measure HGS. We also provided a minimum reporting criteria framework to help future research studies avoid underreporting of HGS procedures.

International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines.

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.

Identifying Biomarkers for Biological Age: Geroscience and the ICFSR Task Force.

The International Conference on Frailty and Sarcopenia Research Task Force met in March 2020, in the shadow of the COVID-19 pandemic, to discuss strategies for advancing the interdisciplinary field of geroscience. Geroscience explores biological mechanisms of aging as targets for intervention that may delay the physiological consequences of aging, maintain function, and prevent frailty and disability. Priorities for clinical practice and research include identifying and validating a range of biomarkers of the hallmarks of aging. Potential biomarkers discussed included markers of mitochondrial dysfunction, proteostasis, stem cell dysfunction, nutrient sensing, genomic instability, telomere dysfunction, cellular senescence, and epigenetic changes. The FRAILOMICS initiative is exploring many of these through various omics studies. Translating this knowledge into new therapies is being addressed by the U.S. National Institute on Aging Translational Gerontology Branch. Research gaps identified by the Task Force include the need for improved cellular and animal models as well as more reliable and sensitive measures.

Osteoporosis in Frail Older Adults: Recommendations for Research from the ICFSR Task Force 2020.

Interactions among physiological pathways associated with osteoporosis and sarcopenia are thought to contribute to the onset of frailty. The International Conference on Frailty and Sarcopenia Research Task Force thus met in March 2020 to explore how emerging interventions to manage fracture and osteoporosis in older adults may reduce frailty, disability, morbidity, and mortality in the older population. Both pharmacological and non-pharmacological interventions (including nutritional intervention, exercise, and other lifestyle changes) were discussed, including nutritional intervention, exercise, and other lifestyle changes. Pharmacological treatments for osteoporosis include bone-forming and antiresorptive agents, which may optimally be used in sequential or combination regimens. Since similar mechanisms related to resorption underlie physiological changes in muscle and bone, these interventions may provide benefits beyond treating osteoporosis. Clinical trials to test these interventions, however, often exclude frail older persons because of comorbidities (such as mobility disability and cognitive impairment) or polypharmacy. The Task Force recommended that future clinical trials use harmonized protocols, including harmonized inclusion criteria and similar outcome measures; and that they test a range of multidomain therapies. They further advocated more high-quality research to develop interventions specifically for people who are frail and old. The ICOPE program recommended by WHO appears to be highly recommended to frail older adults with osteoporosis.

URBAN-RURAL DIFFERENCES IN THE PREVALENCE OF MUSCLE WEAKNESS AND SLOW GAIT SPEED: A CROSS-SECTIONAL ANALYSIS FROM THE NHANES (2001-2002 AND 2011-2014).

Background: Older adults living in rural areas suffer from health inequities compared to their urban counterparts. These include comorbidity burden, poor diet, and physical inactivity, which are also risk factors for sarcopenia, for which muscle weakness and slow gait speed are domains. To date, no study has examined urban-rural differences in the prevalence of muscle weakness and slow gait speed in older adults living in the United States. Objective: To compare the prevalence of grip strength weakness and slow gait speed between urban and rural older adults living in the United States. Design: A cross-sectional, secondary data analysis of two cohorts from the National Health and Nutrition Examination Survey (NHANES), using gait speed or grip strength data, and urban-rural residency, dietary, examination, questionnaire and demographic data. Participants: 2,923 adults (≥ 60 yrs.). Measures: Grip weakness was defined as either, an absolute grip strength of <35 kg. and <20 kg. or grip strength divided by body mass index (GripBMI) of <1.05 and <0.79 for men and women, respectively. Slow gait speed was defined as a usual gait speed of ≤0.8m/s. Results: The prevalence of GripBMI weakness was significantly higher in urban compared to rural participants (27.4% vs. 19.2%; p=0.001), whereas their absolute grip strength was lower (31.75(±0.45) vs. 33.73(±0.48)). No urban-rural differences in gait speed were observed. Conclusions: Older adults residing in urban regions of the United States were weaker compared to their rural counterparts. This report is the first to describe urban-rural differences in handgrip strength and slow gait speed in older adults living in the United States.

Rationale and study design for lifestyle intervention in preparation for pregnancy (LIPP): A randomized controlled trial.

INTRODUCTION: Maternal obesity increases neonatal risk for obesity and metabolic syndrome later in life. Prior attempts to break this intergenerational obesity cycle by limiting excessive gestational weight gain have failed to reduce neonatal adiposity. Alternatively, pre-conception lifestyle interventions may improve the in utero metabolic milieu during early pregnancy leading to improved fetal outcomes. This randomized controlled trial (RCT) is evaluating whether a lifestyle intervention to reduce weight and improve maternal metabolism in preparation for pregnancy (LIPP) attenuates neonatal adiposity, compared to standard medical advice. MATERIAL AND METHODS: Overweight/class 1 obese women after a previous pregnancy, ~12 weeks postpartum, preparing for a subsequent pregnancy, will be block randomized (1:1) to either LIPP or standard of care in a parallel design. Randomization is stratified by lactation status and overweight vs. class 1 obesity. The LIPP program consists of intensive short-term weight loss followed by weight maintenance until conception using supervised exercise and a low glycemic Mediterranean diet. PRIMARY OUTCOMES: Group differences in neonatal adiposity at birth assessed by PEA POD and placental mitochondrial lipid metabolism. SECONDARY OUTCOMES: Group differences in maternal pregravid and gestational body composition, insulin sensitivity, ß-cell function, fasting metabolic and inflammatory biomarkers, and overall quality of life. Exploratory outcomes include umbilical cord blood insulin resistance, lipid profile and inflammation. DISCUSSION: This RCT will determine the efficacy of maternal weight loss prior to pregnancy on reducing neonatal adiposity. Findings may change standard obstetrical care by providing Level 1 evidence on lifestyle interventions improving neonatal outcomes for women planning for pregnancy. CLINICAL TRIAL REGISTRATION: NCT03146156.

ICFSR Task Force Perspective on Biomarkers for Sarcopenia and Frailty.

Biomarkers of frailty and sarcopenia are essential to advance the understanding of these conditions of aging and develop new diagnostic tools and effective treatments. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force - a group of academic and industry scientists from around the world -- met in February 2019 to discuss the current state of biomarker development for frailty and sarcopenia. The D3Cr dilution method, which assesses creatinine excretion as a biochemical measure of muscle mass, was suggested as a more accurate measure of functional muscle mass than assessment by dual energy x-ray absorptiometry (DXA). Proposed biomarkers of frailty include markers of inflammation, the hypothalamic-pituitary-adrenal (HPA) axis response to stress, altered glucose insulin dynamics, endocrine dysregulation, aging, and others, acknowledging the complex multisystem etiology that contributes to frailty. Lack of clarity regarding a regulatory pathway for biomarker development has hindered progress; however, there are currently several international efforts to develop such biomarkers as tools to improve the treatment of individuals presenting these conditions.

Circulating Interleukin-6 Is Associated with Skeletal Muscle Strength, Quality, and Functional Adaptation with Exercise Training in Mobility-Limited Older Adults.

BACKGROUND: Human aging is characterized by a chronic, low-grade inflammation suspected to contribute to reductions in skeletal muscle size, strength, and function. Inflammatory cytokines, such as interleukin-6 (IL-6), may play a role in the reduced skeletal muscle adaptive response seen in older individuals. OBJECTIVES: To investigate relationships between circulating IL-6, skeletal muscle health and exercise adaptation in mobility-limited older adults. DESIGN: Randomized controlled trial. SETTING: Exercise laboratory on the Health Sciences campus of an urban university. PARTICIPANTS: 99 mobility-limited (Short Physical Performance Battery (SPPB) ≤9) older adults. INTERVENTION: 6-month structured physical activity with or without a protein and vitamin D nutritional supplement. MEASUREMENTS: Circulating IL-6, skeletal muscle size, composition (percent normal density muscle tissue), strength, power, and specific force (strength/CSA) as well as physical function (gait speed, stair climb time, SPPB-score) were measured pre- and post-intervention. RESULTS: At baseline, Spearman's correlations demonstrated an inverse relationship (P<0.05) between circulating IL-6 and thigh muscle composition (r = -0.201), strength (r = -0.311), power (r = -0.210), and specific force (r = -0.248), and positive association between IL-6 and stair climb time (r = 0.256; P<0.05). Although the training program did not affect circulating IL-6 levels (P=0.69), reductions in IL-6 were associated with gait speed improvements (r = -0.487; P<0.05) in "higher" IL-6 individuals (>1.36 pg/ml). Moreover, baseline IL-6 was inversely associated (P<0.05) with gains in appendicular lean mass and improvements in SPPB score (r = -0.211 and -0.237, respectively). CONCLUSIONS: These findings implicate age-related increases in circulating IL-6 as an important contributor to declines in skeletal muscle strength, quality, function, and training-mediated adaptation. Given the pervasive nature of inflammation among older adults, novel therapeutic strategies to reduce IL-6 as a means of preserving skeletal muscle health are enticing.