Physical Frailty In Older People Research Articles

The sarcopenia and physical frailty in older people: multi-component treatment strategies (SPRINTT) project: description and feasibility of a nutrition intervention in community-dwelling older Europeans

AimTo describe the methods and feasibility of the nutritional intervention carried out within the SPRINTT Randomized cotrolled trial. We also illustrate how nutrition interventionists identified participants at risk of malnutrition and the lessons learnt from the nutrition intervention.FindingsSPRINTT nutrition intervention was well-received by the majority of the participants. It was mainly carried out using tailored nutrition counselling, but also other means of delivering the intervention were successfully used. Compared with a standard nutrition prescription, an individualized protocol to diagnose malnutrition and follow-up by tailored nutrition counselling helped achieve nutritional targets more effectively in spite of diversity of population in nutritional habits and in some cases reluctance to accept changes.MessageThe SPRINTT nutrition intervention was feasible and allowed flexibility to the varying needs and cultural differences of this heterogeneous population of frail, older Europeans. It may serve as a model to educate and improve nutrition among community-dwelling older people at risk of mobility limitations.

EWGSOP 1 and EWGSOP 2 criteria – Comparison and its use for diagnosing of sarcopenic obesity in over 70 years old patients

Rationale: The aim of this study is to validate the new diagnostic algorithm of sarcopenia EWGSOP-2 (2019) and compare it to the EWGSOP-1 (2010); further to describe prevalence of sarcopenia and sarcopenic obesity (SO) in patients screened for SPRINTT study (The “Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies”).

Interaction of Skeletal and Left Ventricular Mass in Older Adults with Low Muscle Performance.

It was recently hypothesized the existence of "cardiac-skeletal muscle axis." However, the relationship between skeletal muscle mass (SMM) and left ventricular mass (LVM) has never been investigated in the specific group of older individuals with low skeletal mass and physical performance. We tested this hypothesis in the SPRINT-T (Sarcopenia and Physical Frailty IN older people: multicomponenT Treatment strategies Trial) population using LVM as independent variable and SMM as dependent variable. SMM was assessed by dual-energy X-ray absorptiometry scan and expressed as appendicular lean mass (ALM), and LVM was estimated through echocardiography. Low ALM was defined according to Foundation for the National Institutes of Health Sarcopenia Project criteria, and Short Physical Performance Battery (SPPB) was used to assess physical performance. The population consisted of 100 persons (33 men and 67 women), aged 70 years or older (mean age = 79 ± 5 years) with low ALM and SPPB ranged between 3 and 9, suggestive of physical frailty. Charlson Comorbidity Index median score was 0. Mean value of LVM was 193 ± 67 g, indexed LVM/body surface area (LVM/BSA) was 112 ± 33 g/m2, and cardiac output (CO) was 65 ± 19 L/min. ALM was strongly and positively correlated with LVM (r = 0.54602; P < .0001), LVM/BSA (r = 0.30761; P < .002), CO (r = 0.49621; P < .0001), body mass index (BMI) (r = 0.52461; P < .0001), sex (r = 0.77; P < .001), fat mass (r = 0.38977; P < .0001), and hemoglobin (Hb) (r = 0.26001; P < .01). In the multivariate analysis, LVM (β = .019 ± .005; P < .0001), CO (β = .038 ± .016; P = .019), BMI (β = .286 ± .051; P < .0001), and Hb (β = .544 ± .175; P = .0025) remained associated to ALM. In a sample of older persons with low muscle mass and physical performance, LVM was positively and significantly correlated with ALM, independently from blood pressure, physical activity, and other potential confounders. Future studies are needed to address the effect of interventions targeting LVM and SMM.

The “Function vs. Disease Dilemma” in Contemporary Medicine: Physical Frailty &amp; Sarcopenia as a Prototypic Condition of New‐Generation Geriatric Medicine

Due to the worldwide demographic transition, healthcare systems are facing new demands. Health services—with their approach of mostly single acute conditions—are indeed confronted with an expanding older population characterized by specific medical needs related to multimorbidity and functional impairment. The European research project “Sarcopenia and Physical fRailty IN older people: multi‐componenT Treatment strategies” (SPRINTT) project is specifically designed to overcome existing barriers for efficient public health interventions against frailty, and promote the implementation of successful aging strategies across Europe. The just‐completed SPRINTT randomized clinical trial (RCT) compared the efficacy of a multicomponent intervention (based on long‐term structured physical activity, nutritional counselling, and an information and communication technology intervention) versus a Healthy Aging Lifestyle Education program for preventing incident mobility disability in community‐dwelling older persons with physical frailty and sarcopenia. For the RCT, we enrolled 1,517 community‐dwellers, aged 70 years and older (750 per treatment arm), non‐disabled older persons exposed to increased vulnerability to stressors. The identification of such population relied on three key elements: low muscle mass measured by DXA (identified using FNIH cutpoints); clinical signs of physical frailty (i.e., weakness, slow walking speed, and poor balance) assessed using SPPB; absence of major mobility disability (able to walk 400 meters within 15 minutes at baseline. The primary outcome was the incidence of mobility disability (i.e., incident inability to walk 400 meters). Secondary outcomes included, among others, changes in physical performance and function; ability of selected biomarkers to predict the rate of change in muscle mass; incidence of falls. The SPRINTT RCT was conducted in 15 study sites located in nine European countries. The mean age of our sample was 79 years (SD ± 5.8), 72% were women, BMI was 28.6 kg/m2 (± 5.9), with 37% of the population showing BMI &gt;30 kg/m2, Handgrip strength was 20.1 kg (SD 8.2), SPPB score was 6.71 (SD 1.4), aLM in men was 21.0 kg (SD 4.06) and 15.0 kg in women (SD 1.98), the aLM/BMI was 0.71 (SD 0.06) in men and 0.51 (SD 0.07) in women. Data analysis is ongoing and final results may be available at the date of the EB meeting.Support or Funding InformationInnovative Medicines Initiative – Joint Undertaking (IMI‐JU 115621)

DNA methylation and the epigenetic clock in relation to physical frailty in older people: the Lothian Birth Cohort 1936

BackgroundThe biological mechanisms underlying frailty in older people are poorly understood. There is some evidence to suggest that DNA methylation patterns may be altered in frail individuals.MethodsParticipants were 791 people aged 70 years from the Lothian Birth Cohort 1936. DNA methylation was measured in whole blood. Biological age was estimated using two measures of DNA methylation-based age acceleration-extrinsic and intrinsic epigenetic age acceleration. We carried out an epigenome-wide association study of physical frailty, as defined by the Fried phenotype. Multinomial logistic regression was used to calculate relative risk ratios for being physically frail or pre-frail according to epigenetic age acceleration.ResultsThere was a single significant (P = 1.16 × 10–7) association in the epigenome-wide association study comparing frail versus not frail. The same CpG was not significant when comparing pre-frail versus not frail. Greater extrinsic epigenetic age acceleration was associated with an increased risk of being physically frail, but not of being pre-frail. For a year increase in extrinsic epigenetic age acceleration, age- and sex-adjusted relative risk ratios (95% CI) for being physically frail or pre-frail were 1.06 (1.02, 1.10) and 1.02 (1.00, 1.04), respectively. After further adjustment for smoking and chronic disease, the association with physical frailty remained significant. Intrinsic epigenetic age acceleration was not associated with physical frailty status.ConclusionsPeople who are biologically older, as indexed by greater extrinsic epigenetic age acceleration, are more likely to be physically frail. Future research will need to investigate whether epigenetic age acceleration plays a causal role in the onset of physical frailty.

Multidimensional predictors of physical frailty in older people: identifying how and for whom they exert their effects

Physical frailty in older people is an escalating health and social challenge. We investigate its physical, psychological, and social predictors, including how and for whom these conditions exert their effects. For 4638 respondents aged 65–89 years from wave 2 of the English Longitudinal Study of Ageing, we examine prediction of future physical frailty by physical, psychological, and social conditions using latent growth curve analysis with multiple indicators. In addition, we explore their indirect effects through disease and physiologic decline, and repeat these analyses after stratification by gender, age group, and selected conditions which are possible moderators. We find that chronic disease, allostatic load, low physical activity, depressive symptoms, cognitive impairment, and poor social support all predict future physical frailty. Furthermore, chronic disease and allostatic load mediate the effects of low physical activity, depressive symptoms, and cognitive impairment on future physical frailty. Finally, although poor social integration is not a predictor of future physical frailty, this condition moderates the indirect effect of poor social support through chronic disease by rendering it stronger. By virtue of their roles as predictor, mediator, or moderator on pathways to physical frailty, chronic disease, allostatic load, low physical activity, cognitive impairment, depressive symptoms, poor social support, and poor social integration are potentially modifiable target conditions for population-level health and social interventions to reduce future physical frailty in older people.

Nutrition, frailty, and sarcopenia.

Frailty and sarcopenia are important concepts in the quest to prevent physical dependence, as geriatrics are shifting towards identifications of early stages of disability. Definitions of both sarcopenia and frailty are still developing, and both concepts clearly overlap in their physical aspects. Malnutrition (both undernutrition and obesity) plays a key role in the pathogenesis of frailty and sarcopenia. The quality of the diet along the lifespan has a close relation with the incidence of both entities, and nutritional interventions may be able to reduce the incidence or revert either of them. This brief review explores the role of energy and protein intake and other key nutrients on muscle function. Nutrition may be a key element of multimodal interventions for frailty and sarcopenia. The results of the "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) trial will offer key insights on the effect of such interventions in frail, sarcopenic older individuals.

Sarcopenia: an overview.

Sarcopenia, the age-dependent loss of muscle mass and function, is a common condition among older adults, and is associated with several adverse health outcomes. Owing to the impact of sarcopenia on quality of life, disability and mortality, a greater awareness is necessary in order to correctly identify the condition both in community and geriatric settings. Research on sarcopenia prevention and treatment is developing quickly, but many questions are still unanswered. The core of the sarcopenia condition involves quantitative and qualitative losses of skeletal muscle. These two dimensions should therefore be considered when designing and testing preventive and therapeutic interventions. The recently released operationalization of sarcopenia by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project allows for the framing of an objective, standardized, and clinically relevant condition, which should facilitate its translation into the clinical arena as well as its adoption by public health and regulatory agencies. Such a conceptualization might eventually encourage key stakeholders to combine their efforts in approaching the sarcopenia condition. Bearing these considerations in mind, the "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" project has operationalized a specific condition, named physical frailty and sarcopenia (PF&S), characterized by the combination of low physical performance (based on the Short Physical Performance Battery) and low muscle mass (according to the FNIH cut-points). A randomized controlled trial will be conducted to evaluate the efficacy of a multi-component intervention for preventing mobility disability and other adverse health outcomes in older adults with PF&S.

Rationale for a preliminary operational definition of physical frailty and sarcopenia in the SPRINTT trial.

In the present article, the rationale that guided the operationalization of the theoretical concept of physical frailty and sarcopenia (PF&S), the condition of interest for the "Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies" (SPRINTT) trial, is presented. In particular, the decisions lead to the choice of the adopted instruments, and the reasons for setting the relevant thresholds are explained. In SPRINTT, the concept of physical frailty is translated with a Short Physical Performance Battery score of ≥3 and ≤9. Concurrently, sarcopenia is defined according to the recent definitions of low muscle mass proposed by the Foundation for the National Institutes of Health-Sarcopenia Project. Given the preventive purpose of SPRINTT, older persons with mobility disability (operationalized as incapacity to complete a 400-m walk test within 15min; primary outcome of the trial) at the baseline are not included within the diagnostic spectrum of PF&S.

Physical frailty and sarcopenia (PF&S): a point of view from the industry.

We have observed over the last 15years a wide debate both in the medical scientific community and in the public health arena on the definition and operationalization of frailty, typically a geriatric condition, and in particular of physical frailty linked to sarcopenia. Because physical frailty in its initial phase can still be reversed, fighting sarcopenia in elderly persons has the potential to slow or halt progressive decline towards disability and dependency. Quite recently, regulators focused attention on frailty as an indicator of biological age to be measured to characterize elderly patients before their inclusion in clinical trials. A European guidance regarding most adapted evaluation instruments of frailty is currently under public consultation. Does the regulatory initiative imply we should now consider frailty, and particularly physical frailty, primarily as an important risk factor for adverse events and poor response, or mainly as a clinical tool helping the physician to opt for one therapeutic pathway or another? Or is physical frailty above all a specific geriatric condition deserving an effective and innovative therapeutic approach with the objective to curb the incidence of its most common result, e.g., mobility disability? Pharmaceutical industry developers consider both faces of the coin very relevant. We agree with regulators that better characterization of subpopulations, not only in elderly patients, can improve the benefit risk ratio of medicines. At the same time, we believe it is in the public health interest to develop novel drugs indicated for specific geriatric conditions, like osteoporosis in the 1990s and sarcopenia today. We consider it an important therapeutic goal to effectively delay mobility disability and to extend the active, independent, and healthy life years of aging people. The "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) collaborative project under IMI is paving the way for adapted methodologies to study the change of physical frailty and sarcopenia in at-risk older persons and to adequately characterize the population that needs to be treated.

Preventing mobility disability in Europe: a health economics perspective from the SPRINTT study

In a global context of population aging, gaining better knowledge of the mechanisms leading to loss of autonomy has become a major objective, notably with the aim of implementing effective preventive health policies. The concept of frailty, originally introduced in gerontology and geriatrics as a precursor state to functional dependency, appears as a useful tool in this specific context. The "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) project will provide a unique opportunity to explore health economics issues associated with frailty. In terms of health economics, the loss of autonomy approach retained here focuses on the economic and social causes and consequences of the onset of frailty in older adults, and examines the challenges not only in terms of health system efficiency but also in terms of social protection.

The need of operational paradigms for frailty in older persons: the SPRINTT project.

The exploration of frailty as a pre-disability geriatric condition represents one of the most promising research arenas of modern medicine. Frailty is today indicated as a paradigmatic condition around which the traditional healthcare systems might be re-shaped and optimized in order to address the complexities and peculiarities of elders. Unfortunately, the lack of consensus around a single operational definition has limited the clinical implementation of frailty in clinical practice. In these last years, growing attention (even beyond the traditional boundaries of geriatric medicine) has been given to physical performance measures. These instruments have shown to be predictive of negative health-related events and able to support an accurate estimation of the "biological age" in late life. The strong construct of physical performance measures also makes them particularly suitable for the assessment of the frailty status. Furthermore, the adoption of physical performance measures may help render the frailty condition more organ-specific (i.e., centred on the skeletal muscle quality) and less heterogeneous than currently perceived. The translation of the frailty concept by means of physical performance measures implicitly represents an attempt to go beyond traditional paradigms. In this context, the recently funded "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) project (largely based on such a novel approach) may indeed fill an important gap in the field and provide key insights for counteracting the disabling cascade in the elderly.

SPRINTT and the involvement of stakeholders: strategy and structure.

The current healthcare systems are built around the traditional paradigm of patients suffering from a single acute illness. They are, therefore, largely unprepared to face the increasing demands for health services arising from the expansion of an older population with specific medical needs related to multiple chronic disorders. As a consequence, the medical conditions of a large and growing segment of the older European population are not efficiently managed by the available healthcare services. In the context of an aging population, policy makers such as the European Commission and European Institutions, such as the European Medicines Agency (EMA), devote time and resources to study and accompany the need of the aging population. The EMA recognizes the importance of making sure that the needs of the Elderly are considered during development, approval, and use of new medicines, and, therefore, engages with healthcare professional organisations. The Sarcopenia and Physical Frailty in Older People: Multicomponent Intervention Strategies (SPRINTT) is the obvious result of these strategies. The present article describes the SPRINTT workpackage activities aimed at engaging the scientific discussion on the physical frailty and sarcopenia with the EMA as one of its interlocutor, acknowledging the need to collaborate on this topic to foster a productive dialogue.

Exercise and Protein Intake: A Synergistic Approach against Sarcopenia.

Sarcopenia, the age-dependent loss of muscle mass and function/strength, is increasingly recognized as a major risk factor for adverse outcomes in frail older people. As such, the skeletal muscle is a relevant target for interventions aimed at preventing or postponing the occurrence of negative health-related events in late life. The association among physical inactivity, insufficient intake of energy and protein, and poor muscle health in older adults suggests that physical exercise and targeted nutritional supplementation may offer substantial therapeutic gain against sarcopenia and its negative correlates. This view is supported by observational studies as well as by small-scale clinical trials. In this review, we summarize the available evidence on the beneficial effects of behavioral interventions on sarcopenia. We also briefly describe how the knowledge gathered so far has been used to design the “Sarcopenia and Physical fRailty IN older people: multicomponenT Treatment strategies” (SPRINTT) project. The randomized clinical trial conducted within SPRINTT will provide robust evidence on the effectiveness of exercise and nutrition at preventing negative outcomes associated with sarcopenia and physical frailty.

Balance quality assessment as an early indicator of physical frailty in older people.

Frailty is an increasingly common geriatric condition that results in an increased risk of adverse health outcomes such as falls. The most widely-used means of detecting frailty is the Fried phenotype, which includes several objective measures such as grip strength and gait velocity. One method of screening for falls is to measure balance, which can be done by a range of techniques including the assessment of the Centre of Pressure (CoP) during a balance assessment. The Balance Quality Tester (BQT) is a device based on a commercial bathroom scale that can evaluate balance quality. The BQT provides instantaneously the position of the CoP (stabilogram) in both anteroposterior (AP) and mediolateral (ML) directions and can estimate the vertical ground reaction force. The purpose of this study was to examine the relationship between balance quality assessment and physical frailty. Balance quality was compared to physical frailty in 186 older subjects. Rising rate (RR) was slower and trajectory velocity (TV) was higher in subjects classified as frail for both grip strength and gait velocity (p<;0.05). Balance assessment could be used in conjunction with functional tests of grip strength and gait velocity as a means of screening for frailty.

Physical frailty in older people with severe aortic stenosis.

Assessment of physical frailty is important among elderly with severe aortic stenosis (AS) when considering treatment. We aimed to: (1) investigate the prevalence of physical frailty in older people with severe AS and (2) examine factors related to physical frailty. A total of 125 consecutive elderly AS patients (mean age 84.6±4.4year) were enrolled. Physical frailty was defined as scoring ≤8 points on the short physical performance battery (SPPB). Factors likely related to physical frailty, including cardiac function, nutritional and metabolic status, kidney function, medical history, and comorbidities, were evaluated. Logistic regression analyses were used to examine which factors were related to physical frailty. Physical frailty was prevalent in 38.4%. After sex and age adjusted, the following were significantly related to physical frailty: LVEF (adjusted OR per 10% decrease: 1.39, p<0.05), the Mini Nutritional Assessment-Short Form (adjusted OR per 1 point decrease: 1.21, p<0.05), serum albumin (adjusted OR per 1g/dL decrease: 2.64, p<0.05), HDL-C (adjusted OR per 10mg/dL decrease: 1.52, p<0.01), eGFR (adjusted OR per 10mL/min decrease: 1.59, p<0.05), grip strength (adjusted OR per 10kg decrease: 3.60, p<0.01), coronary heart disease (adjusted OR: 2.78, p<0.01), cerebrovascular disease (adjusted OR: 6.06, p<0.01), and musculoskeletal disorders (adjusted OR: 3.28, p<0.01). The prevalence of physical frailty is high and related to nutritional status, comorbidities, and cardiac status.

Physical frailty and sarcopenia: taking advantage of their commonalities

Physical frailty and sarcopenia are two agerelated conditions indicated as key risk factors for incident disability and health-related negative events in the elderly. Nevertheless, to date, their clinical implementation is still limited, largely because of methodological ambiguities and disagreement about their operationalizations. In order to bypass the current stall-position in the field and try to identify an objective, standardized, and clinically relevant target for interventions, it might be hypothesized to redesign the limits of a pre-disability &lt;em&gt;physical&lt;/em&gt; risk condition around the inner core shared by both physical frailty and sarcopenia. Thus, preliminary research initiatives [like the &lt;em&gt;sarcopenia and physical frailty in older people: multicomponent treatment strategies&lt;/em&gt; (SPRINTT) project] are proposing to explore whether physical frailty (or poor physical performance) may represent the clinical manifestation of a specific biological substratum (&lt;em&gt;i.e&lt;/em&gt;., low muscle mass) on which build up novel interventions against disability in the elderly.

Framingham cardiovascular disease risk scores and incident frailty: the English longitudinal study of ageing.

Cross-sectional studies show that frailty is common in older people with cardiovascular disease. Whether older people at higher risk of developing cardiovascular disease are more likely to become frail is unclear. We used multinomial logistic regression to examine the prospective relation between Framingham cardiovascular disease risk scores and incidence of physical frailty or pre-frailty, defined according to the Fried criteria, in 1,726 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing who had no history of cardiovascular disease at baseline. Men and women with higher Framingham cardiovascular risk scores were more likely to become frail over the 4-year follow-up period. For a standard deviation higher score at baseline, the relative risk ratio (95 % confidence interval) for incident frailty, adjusted for sex and baseline frailty status, was 2.76 (2.18, 3.49). There was a significant association between Framingham cardiovascular risk score and risk of pre-frailty: 1.69 (1.46, 1.95). After further adjustment for other potential confounding factors, the relative risk ratios for frailty and pre-frailty were 2.15 (1.68, 2.75) and 1.50 (1.29, 1.74), respectively. The associations were unchanged after excluding incident cases of cardiovascular disease. Separate adjustment for each component of the risk score suggested that no single component was driving the associations between cardiovascular risk score and incident pre-frailty or frailty. Framingham cardiovascular risk scores may be useful for predicting the development of physical frailty in older people. We now need to understand the biological mechanisms whereby cardiovascular risk increases the risk of frailty.

Low-grade chronic inflammation and superoxide anion production by NADPH oxidase are the main determinants of physical frailty in older adults

Background. Physical performance measured by gait speed is being recognized as a major instrument for clinical evaluation in older adults, because it predicts physical frailty, loss of autonomy, hospitalization and decreased survival. Low-grade chronic inflammation and oxidative stress, mediated partly by the superoxide anion produced by NADPH oxidase, are closely linked and could be involved in age-related physical decline. Objective. To determine whether slow gait speed is associated with superoxide anion overproduction by NADPH oxidase and low-grade chronic inflammation. Design and setting. Observational study among the 280 elderly of an ambulatory geriatric care unit (191 women, 89 men, 79.9 ± 6.1 years old). Methods. Gait speed was evaluated by walking at self-chosen usual pace. Usual gait speed < 0.8 m/s was defined as slow gait speed. Superoxide anion production was evaluated using a lucigenin-based chemiluminescence method. Inflammation was evaluated by CRP, fibrinogen and leukocyte count. Results. Among the 280 participants, 179 (63.9%) walked with a gait speed < 0.8 m/s (slow walkers) and 101 (36.1%) with a gait speed ≥ 0.8 m/s. Superoxide production and inflammation markers, such as fibrinogen, were more important in slow walkers (p = 0.004 and p = 0.006, respectively). In multivariate analysis, superoxide anion overproduction and fibrinogen were independently associated with physical frailty assessed by slow gait speed (p = 0.028 and p = 0.007, respectively). Conclusion. Physical frailty in older people is associated with superoxide anion overproduction by NADPH oxidase and low-grade chronic inflammation.

Monitoring of physical frailty in older people: An innovative system supporting self- man-agement and care

Monitoring of physical frailty in older people: An innovative system supporting self- man-agement and care