Clinically Meaningful Change for Physical Performance: Perspectives of the ICFSR Task Force Abstract For clinical studies of sarcopenia and frailty, clinically meaningful outcome measures are needed to monitor disease progression, evaluate efficacy of interventions, and plan clinical trials. Physical performance measures including measures of gait speed and other aspects of mobility and strength have been used in many studies, although a definition of clinically meaningful change in performance has remained unclear. The International Conference on Frailty and Sarcopenia Research Task Force (ICFSR-TF), a group of academic and industry scientists investigating frailty and sarcopenia, met in Miami Beach, Florida, USA in February 2019 to explore approaches for establishing clinical meaningfulness in a manner aligned with regulatory authorities. They concluded that clinical meaningful change is contextually dependent, and that both anchor- based and distribution-based methods of quantifying physical function are informative and should be evaluated relative to patient-reported outcomes. In addition, they identified additional research needed to enable setting criteria for clinical meaningful change in trials.

ICFSR Task Force Perspective on Biomarkers for Sarcopenia and Frailty Abstract 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.

The Association of Frailty with Hospitalizations and Mortality Among Community Dwelling Older Adults with Diabetes Abstract Background Diabetes (DM) is associated with an accelerated aging that promotes frailty, a state of vulnerability to stressors, characterized by multisystem decline that results in diminished intrinsic reserve and is associated with morbidity, mortality and utilization. Research suggests a bidirectional relationship between frailty and diabetes. Frailty is associated with mortality in patients with diabetes, but its prevalence and impact on hospitalizations are not well known. Objectives Determine the association of frailty with allcause hospitalizations and mortality in older Veterans with diabetes. Design: Retrospective cohort. Setting Outpatient. Participants Veterans 65 years and older with diabetes who were identified as frail through calculation of a 44-item frailty index. Measurements The FI was constructed as a proportion of healthcare variables (demographics, comorbidities, medications, laboratory tests, and ADLs) at the time of the screening. At the end of follow up, data was aggregated on all-cause hospitalizations and mortality and compared non-frail (robust, FI≤.10 and prefrail FI=>.10, <.21) and frail (FI≥.21) patients. After adjusting for age, race, ethnicity, median income, history of hospitalizations, comorbidities, duration of DM and glycemic control, the association of frailty with all-cause hospitalizations was carried out according to the Andersen-Gill model, accounting for repeated hospitalizations and the association with all-cause mortality using a multivariate Cox proportional hazards regression model. Results We identified 763 patients with diabetes, mean age 72.9 (SD=6.8) years, 50.5% were frail. After a median follow-up of 561 days (IQR=172), 37.0% they had 673 hospitalizations. After adjustment for covariates, frailty was associated with higher all-cause hospitalizations, hazard ratio (HR)=1.71 (95%CI:1.31–2.24), p<.0001, and greater mortality, HR=2.05 (95%CI:1.16–3.64), p=.014. Conclusions Frailty was independently associated with all-cause hospitalizations and mortality in older Veterans with diabetes. Interventions to reduce the burden of frailty may be helpful to improve outcomes in older patients with diabetes.

Discordance about Frailty Diagnosis between Surrogates and Physicians and its relationship to Hospital Mortality in Critically Ill Older Adults Abstract The preponderance of studies on frailty assessment in critically ill adults have used the Clinical Frailty Scale (CFS) to quantify frailty and previous research suggests that surrogates were more likely to be optimistic than physicians in their CFS scores. Whether discordance between surrogates and physicians was relevant to prognosis has been underexplored. Therefore, in a prospective observational cohort of 298 critically ill older adults, we aimed 1) to describe factors related to discordance and 2) to estimate the relationship between such discordance and hospital mortality and other short-term outcomes. Discordance between surrogates and physician was present in 89/298 (29.9%) and independently associated with a higher risk of hospital mortality. Discordance was not associated with markers of intensity of treatment such as intubation, blood transfusion, incident dialysis for acute renal failure and prolonged hospital length of stay. Understanding factors relevant to discordance between physicians and surrogates may lend further insights into short-term prognosis for older adults with critical illness.

Drug-Induced Hyponatremia: NSAIDs, a Neglected Cause that Should Be Considered Abstract Hyponatremia is the most common electrolyte disorder. It may have serious consequences in asyntomatic patients with a mild disease. Therefore, an evaluation of unsual causes is of paramount importance. Polypharmacy is highly prevalent in older people and many drugs can cause hyponatremia as a collateral effect. In our retrospective analysis of geriatric medical records dated 2015 we found that 39 out of the 273 hospitalized patients had hyponatremia. Polipharmacy was highly prevalent, especially in hyponatremic patients. Nonsteroidal anti-inflammatory drugs, which are seldom considered as a cause of hyponatremia were instead found to be associated to an increased risk of the disorder (adjustedOR 3.61, 95% CI 1 − 12.99, p = 0.05). In-hospital mortality was higher in patients with moderate or severe hyponatremia at hospital admission. Our study underlines the importance of considering rare but potentially reversible causes of hyponatremia, which can lead to serious consequences.

An Individualized Low-Intensity Walking Clinic Leads to Improvement in Frailty Characteristics in Older Veterans Abstract Background Sedentary lifestyle leads to worse health outcomes with aging, including frailty. Older adults can benefit from regular physical activity, but exercise promotion in the clinical setting is challenging. Objectives The objective of this clinical demonstration project was to implement a Geriatric Walking Clinic for older adults and determine whether this clinical program can lead to improvements in characteristics of frailty. Design This was a clinical demonstration project/quality improvement project. Setting Outpatient geriatrics clinic at the South Texas Veterans Health Care System (STVHCS). Participants Older Veterans, aged ≥60 years. Intervention A 6-week structured walking program, delivered by a registered nurse and geriatrician. Patients received a pedometer and a comprehensive safety evaluation at an initial face-to-face visit. They were subsequently followed with weekly phone calls and participated in a final face-to-face follow-up visit at 6 weeks. Measurements Grip strength (handheld dynamometer), gait speed (10-ft walk), Timed Up and Go (TUG), and body mass index (BMI) were assessed at baseline and follow-up. Frailty status for gait speed was assessed using Fried criteria. Results One hundred eighty five patients completed the program (mean age: 68.4 ±7 years, 88% male). Improvements from baseline to follow-up were observed in average steps/day, gait speed, TUG, and BMI. Improvement in gait speed (1.13 ±0.20 vs. 1.24 ± 0.23 meter/second, p<0.0001) resulted in reduced odds of meeting frailty criteria for slow gait at follow-up compared to the baseline examination (odds ratio = 0.31, 95% confidence interval: 0.13–0.72, p = 0.01). Conclusions Our findings demonstrate that a short duration, low-intensity walking intervention improves gait speed and TUG. This new clinical model may be useful for the promotion of physical activity, and for the prevention or amelioration of frailty characteristics in older adults.

Living with Family Yet Eating Alone is Associated with Frailty in Community-Dwelling Older Adults: The Kashiwa Study Abstract Objectives Eating alone is related to depression, nutritional risk, and mortality. These effects are also influenced by living status. However, little is known about the relationship between eating alone despite living with family and frailty. This study explores the relationship of eating alone and living status with frailty in community-dwelling older adults. Design Cross-sectional study. Setting and Participants Kashiwa city, Chiba prefecture, Japan; randomly selected community-dwelling older adults (aged 65 years and over). Measurements Eating status was assessed by the question, “Do you eat meals with anyone, at least once a day: yes or no?” Frailty was defined by Kihon Checklist (KCL) score 8 or over. Domains of frailty were divided into instrumental activities of daily living (IADL), physical strength, nutrition, eating, socialization, memory, and mood, based on KCL categories. Binary logistic regression analysis was used, adjusting for age, years of education, chronic diseases, number of teeth and cognitive function. Results Among the total of 1,914 participants, 49.8% were male, and the overall mean age was 72.9 ± 5.5 years. Of all participants, 56 (5.9%) of men and 112 (11.7%) of women were frail. Older adults who ate alone despite living with others were more likely to be frail (OR 2.49, 95%CI 1.1–5.5 for men and OR 2.16, 95%CI 1.0–4.5 for women). Of particular note, eating and living status were associated with lower physical strength and mood in men, whereas in women these statuses were associated with lower scores for IADL, socialization, memory, and mood. Conclusions Eating alone despite living with others was associated with high frailty in both genders; however, the pathways were different between genders. These results might help yield a simple, fundamental intervention approach to multifaceted frailty, reflecting gender and associated high-risk domains.

Frailty and the Metabolic Syndrome — Results of the Berlin Aging Study II (BASE-II) Abstract Background Frailty and the metabolic Syndrome (MetS) are frequently found in old subjects and have been associated with increased risk of functional decline and dependency. Moreover, central characteristics of the MetS like inflammation, obesity and insulin resistance have been associated with the frailty syndrome. However, the relationship between MetS and frailty has not yet been studied in detail. Aim of the current analysis within the Berlin Aging Study II (BASE-II) was to explore associations between MetS and frailty taking important co-variables such as nutrition (total energy intake, dietary vitamin D intake), physical activity and vitamin D-status into account. Methods Complete cross-sectional data of 1,486 old participants (50.2% women, 68.7 (65.8–71.3) years) of BASE-II were analyzed. MetS was defined following the joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity in 2009. Frailty was defined according to the Fried criteria. Limitations in physical performance were assessed via questionnaire, muscle mass was measured using dual energy X-ray absorptiometry (DXA) and grip strength using a Smedley dynamometer. Adjusted regression models were calculated to assess the association between MetS and Frailty. Results MetS was prevalent in 37.6% of the study population and 31.9% were frail or prefrail according to the here calculated frailty index. In adjusted models the odds of being frail/prefrail were increased about 50% with presence of the MetS (OR1.5; 95% CI 1.2,1.9; p= 0.002). Moreover the odds of being prefrail/frail were significantly increased with low HDL-C (OR: 1.5 (95%CI: 1.0–2.3); p = 0.037); and elevated waist circumference (OR: 1.65 (95%CI: 1.1–2.3); p = 0.008). Conclusion The current analysis supports an association between MetS and frailty. There are various metabolic, immune and endocrine alterations in MetS that also play a role in mechanisms underlying the frailty syndrome. To what extent cytokine alterations, inflammatory processes, vitamin D supply and hormonal changes in age and in special metabolic states as MetS influence the development of frailty should be subject of further research.

Can the Combined Use of Two Screening Instruments Improve the Predictive Power of Dependency in (Instrumental) Activities of Daily Living, Mortality and Hospitalization in Old Age? Abstract Background Due to differences in the definition of frailty, many different screening instruments have been developed. However, the predictive validity of these instruments among community-dwelling older people remains uncertain. Objective To investigate whether combined (i.e. sequential or parallel) use of available frailty instruments improves the predictive power of dependency in (instrumental) activities of daily living ((I)ADL), mortality and hospitalization. Design, setting and participants A prospective cohort study with two-year follow-up was conducted among pre-frail and frail community-dwelling older people in the Netherlands. Measurements Four combinations of two highly specific frailty instruments (Frailty Phenotype, Frailty Index) and two highly sensitive instruments (Tilburg Frailty Indicator, Groningen Frailty Indicator) were investigated. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for all single instruments as well as for the four combinations, sequential and parallel. Results 2,420 individuals participated (mean age 76.3 ± 6.6 years, 60.5% female) in our study. Sequential use increased the levels of specificity, as expected, whereas the PPV hardly increased. Parallel use increased the levels of sensitivity, although the NPV hardly increased. Conclusions Applying two frailty instruments sequential or parallel might not be a solution for achieving better predictions of frailty in community-dwelling older people. Our results show that the combination of different screening instruments does not improve predictive validity. However, as this is one of the first studies to investigate the combined use of screening instruments, we recommend further exploration of other combinations of instruments among other study populations.

Relationship of Physical Frailty to Phosphocreatine Recovery in Muscle after Mild Exercise Stress in the Oldest-Old Women Abstract Background Physical frailty is a clinical syndrome associated with aging and manifesting as slowness, weakness, reduced physical activity, weight loss, and/or exhaustion. Frail older adults often report that their major problem is “low energy”, and there is indirect evidence to support the hypothesis that frailty is a syndrome of dysregulated energetics. We hypothesized that altered cellular energy production underlies compromised response to stressors in the frail. Methods We conducted a pilot study to assess muscle energetics in response to a mild isometric exercise challenge in women (n=30) ages 84–93 years. The frailty status was assessed by a validated physical frailty instrument. Localized phosphorus (P31) magnetic resonance spectroscopy with a 1.5T magnet was used to assess the kinetics of Phosphocreatine recovery in the tibialis anterior muscle following maximal isometric contraction for 30 seconds. Results Phosphocreatine recovery following exertion, age-adjusted, was slowest in the frail group (mean=189 sec; 95%CI: 150,228) compared to pre-frail (mean=152 sec; 95%CI: 107,197) and nonfrail subjects (mean=132 sec; 95%CI: 40,224). The pre-frail and frail groups had 20 sec (95%CI: −49,89) and 57 sec (95%CI: −31,147) slower phosphocreatine recovery, respectively, than the non-frail. This response was paralleled by dysregulation in glucose recovery in response to oral glucose tolerance test in women from the same study population. Conclusions Impaired muscle energetics and energy metabolism might be implicated in the physical frailty syndrome.