The Performance and Associated Risks of the Criteria for Sarcopenic Obesity Proposed by the European Association for the Study of Obesity in a Geriatric Population.

BACKGROUND: There is no gold standard definition of sarcopenic obesity (SO). Our objective is to evaluate the benefit of using the new definition proposed by the European Association for the Study of Obesity (EASO) in older people. METHODS: Data from the Toledo Study of Healthy Aging, a study based on a cohort of community-dwelling older adults, were used. SO was defined according to the EASO and by a composite of the Foundation for the National Institute of Health (FNIH) for the diagnosis of sarcopenia and the WHO's criteria for obesity (Body Mass Index, BMI ≥ 30 kg/m2; waist circumference, >88 cm for women and >102 cm for men). Frailty [Frailty Phenotype (FFP) and Frailty Trait Scale-5 (FTS5)] and disability (Katz Index) statuses were assessed at baseline and at the follow-up (median 2.99 years). Mortality at a 5-year follow-up was also assessed. The Logistic and Cox regression models were used to assess the associations. RESULTS: Of the 1559 subjects (age 74.79 ± 5.76 years; 45.54% men), 30.15% (EASO/ESPEN) vs. 16.36% (FNIH) met the SO criteria (Kappa = 0.42). SO was associated with the prevalence of frailty by both the EASO's [OR(95%CI): FFP: 1.70 (1.33-2.16); FTS-5 binary: 2.29 (1.60-3.27); ß(95%CI): FTS-5 continuous 3.63 (3.00-4.27)] and FNIH+WHO's criteria [OR (95%CI): 2.20 (1.61, 3.00)]. The FNIH + WHO's criteria were cross-sectionally associated with disability [OR: 1.52 (1.07, 2.16); p-value 0.018], while the EASO's criteria were not. The EASO's criteria did not show any association at the follow-up, while the FNIH + WHO's criteria were associated with incident frailty. CONCLUSIONS: The EASO's new criteria for sarcopenic obesity demonstrate moderate agreement with the traditional definition and are cross-sectionally associated with adverse events, but they do not effectively predict the outcomes generally associated with sarcopenic obesity in older adults. Therefore, the performance of the EASO's criteria in older people raises the need for refinement before recommending it for generalized use in this population.

Gender-specific capacity of insulin resistance proxies to predict functional decline in older adults.

OBJECTIVES: Insulin resistance determined by Homeostasis Model of Insulin Resistance (HOMA-IR) has been associated with functional decline in non-diabetic older subjects. However, insulin is not routinely assessed. The study evaluated the predictive value of non-insulin-dependent IR surrogates on functional decline in non-diabetic older men and women. DESIGN AND PARTICIPANTS: Prospective cohort study over 5 years. The study included 615 older participants from the Toledo Study of Healthy Aging. METHODS: Frailty was assessed by the Frailty Trait Scale-5 (FTS-5) at baseline and after 5 years follow-up. 193 subjects experienced functional decline (2.5-point reduction in the FTS-5 score). Multivariate regression models analysed the effect of five described IR surrogates on functional decline considering potential confounders. RESULTS: Among evaluated IR proxies, triglyceride glucose-body mass index (TyG-BMI) and HOMA-IR were significantly associated with an increased risk of functional decline (odd ratio (95% confidence interval) TyG-BMI: 1.16 (1.05, 1.28), p = 0.0035 and HOMA-IR: 1.59 (1.15, 2.21), p = 0.0056) among all participants. When stratified by gender, HOMA-IR was related to functional decline in men [2.02 (1.13, 3.59), p = 0.0173] and TyG-BMI in women [1.19 (1.05, 1.35), p = 0.0057]. CONCLUSIONS: Only TyG-BMI index mimics the predictive capacity of insulin-based IR marker. The predictive ability of IR indexes is gender-specific, being TyG-BMI the only index able to predict functional decline in women and HOMA-IR in men.

Impact of frailty, early vascular decline and subclinical cognitive impairment in midlife adults: study protocol of the Toledo Study for Healthy Ageing in middle age.

Life expectancy has increased worldwide alongside a rise in disability prevalence during old age. The impact and interrelationship among the precursors of disability in midlife remain to be better understood. Furthermore, investigating whether lifestyle factors may potentially influence health outcomes and the prognosis of vascular disease could be especially relevant among the middle-aged population, which is a priority subpopulation when prevention is the goal. This is an observational, cross-sectional and population-based study. Participants, between 50 and 55 years old, are randomly selected from the municipality of Toledo (Spain). There are six non-consecutive days for the assessments, providing enough rest between evaluations. Participants perform the interview of the Toledo Study for Healthy Aging. Blood pressure monitoring and a resting electrocardiogram are also recorded. Then, resting peripheral and cerebral vascular measurements along with muscle size and architecture are assessed. Blood and urine samples, and body composition data are collected after an overnight fasting. On a different visit, physical performance and muscle function tests are performed. Additionally, brain magnetic resonance imaging is conducted. And finally, an accelerometer is given to the participants for a week. Frailty is evaluated by Frailty Trait Scale and Fried Frailty Phenotype. This project will shed light on the associations between frailty, early cognitive impairment, and vascular aging during midlife, and on the role that lifestyles play in their development. Lastly, this project will provide meaningful implications for public health strategies aimed at promoting healthy aging in later life.

Relationship of body composition with middle cerebral artery hemodynamic using compositional data analysis: Toledo Study for Healthy Ageing in middle age.

Excess adipose tissue may promote chronic systemic inflammation and oxidative stress, causing endothelial damage. Early evidence indicates that obesity may be associated with poorer cerebral perfusion. The purpose of this study was to examine the relationship between body composition and cerebral hemodynamics. A total of 248 middle-aged adults (50-58 years old; 55% women) underwent a ramp test on a cycle-ergometer until volitional exhaustion. Gas exchange was assessed on a breath-by-breath basis. Mean middle cerebral artery velocity (MCAv) was measured using transcranial Doppler, and pulsatility index (PI) calculated. Body composition was assessed by dual X-ray absorptiometry. Statistical analyses were performed using a compositional data approach including a three-compartment model for body composition (trunk fat mass, extremities fat mass, and fat-free mass). The unadjusted models for the whole sample showed that trunk fat mass relative to other compartments was negatively associated with MCAvrest, MCAvmax, and gain, and positively associated with PImax; extremities fat mass relative to other compartments was positively associated with MCAvrest and MCAvmax, and negatively associated with PImax; and fat-free mass relative to other compartments was positively associated with PImax. These associations were sex-dependent, remaining in the women's subgroup. However, after adjusting for confounders, these associations became non-significant, except for PImax in the whole sample and women's subgroup. These findings suggest a possible association between cerebral hemodynamics and body composition in middle-aged adults, highlighting sex-specific differences. Moreover, our results indicate that higher trunk fat mass relative to other compartments may negatively impact cerebral hemodynamics, reducing MCAv and increasing PImax.

Diagnostic and prognostic value of calf circumference for sarcopenia in community-dwelling older adults.

BACKGROUND: An age-dependent normative values of calf circumference (CC) has been recently proposed as an accessible proxy for muscle mass. However, its usefulness to estimate sarcopenia has not been assessed. The objectives of the present study were to determine if the substitution of the classical way to assess muscle mass by these values have enough diagnostic accuracy and prognostic value among older adults living in the community. METHODS: Data from the Toledo Study of Healthy Ageing (TSHA) were used. CC was measured using an anthropometric tape. We used two age-groups CC cut-off points: the TSHA CC median and the one proposed in the Longevity Check-up 7+ (Lookup 7+) project. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People (EWGSOP2), the Foundation for the National Institutes of Health (FNIH), and FNIH criteria standardized for our population (sFNIH). Frailty (according to the Frailty Phenotype and the Frailty Trait Scale-5) and disability (Katz index) were assessed at baseline and follow-up. Mortality and first hospitalization were also recorded. Logistic (incident frailty and worsening disability) and Cox (mortality and hospitalization) regressions were performed. Diagnostic accuracy was assessed through Kappa index, AUCs, positive and negative predictive values. Predictive ability was assessed through AUCs and integrated AUCs (IAUCs). RESULTS: 1531 participants (74.8 ± 5.8 years; 45.6% men) were included in the analysis. Prevalence rates of sarcopenia were 22.7% (sFNIH), 15.0% (FNIH), and 13.9% (EWGSOP2). Using TSHA-based cut-points of CC, the prevalence of sarcopenia was 16.8% (sFNIH), 11.0% (FNIH), and 11.5% (EWGSOP2). According to LC7+-based CC cut-off points, sarcopenia prevalence was 17.6% (sFNIH), 11.9% (FNIH), and 12.4% (EWGSOP2). CC cut-off points showed low-to-moderate agreement (Kappa Index values between 0.49 and 0.69) with appendicular lean mass for the evaluation of sarcopenia. Sarcopenia identified by Lookup 7+ and TSHA CC cut-off points was associated with the adverse events examined, with similar AUCs and IAUCs than original sarcopenia definitions, and were lost after adjustment by baseline frailty, except when the original EWGSOP2 definition was used. CONCLUSIONS: Using normalized values of CC as a criteria of muscle mass shows moderate agreement with classical criteria for diagnosing sarcopenia and offer similar predictive value in community-dwelling older adults.

Metabolic equivalents intensity thresholds for physical activity classification in older adults.

BACKGROUND: Although the metabolic equivalents (METs) system is a common procedure to quantify the intensity of physical activity in older adults, it remains unclear whether the conventional METs intensity thresholds (CTs) used for this purpose are appropriate in this population. Therefore, this study aimed (i) to derive overall and fitness-specific METs intensity thresholds in older adults ≥ 60 years old (OATs) expressed both in standard METs (VO2/3.5 mL O2·kg-1·min-1) and older adults METs60+ (VO2/2.7 mL O2·kg-1·min-1), and (ii) to compare them with the CTs. METHODS: A total of 93 subjects were assessed for cardiorespiratory fitness. Graded exercise test protocols using indirect calorimetry were performed to calculate individual VO2max and categorize subjects as "very poor/fair" or "good/superior" fitness. Overall and fitness-specific OATs expressed in standard METs (OATsstandard) and METs60+ (OATs60+) were derived based on the %VO2max and the ventilatory thresholds (VTs) physical intensity categories. RESULTS: Significantly higher VO2max, VO2 at VT1 and VO2 at VT2 (p < 0.001) were obtained in the "good/superior" subgroup compared to the "very poor/fair" fitness subgroup. Accordingly, OATs were approximately 69% higher in individuals with a "good/superior" fitness compared to those with a "very poor/fair" fitness. Furthermore, this study showed that OATsstandard were approximately 21-24% lower than OATs60+, and 10-22% higher OATs were observed when following the VTs intensity categories (heavy-intensity physical activity [HPA] and severe-intensity physical activity [SPA]) compared to the %VO2max categories (moderate-intensity physical activity [MPA] and vigorous-intensity physical activity [VPA]). When compared with the CTs, similar or higher OATsstandard and OATs60+ for MPA, and HPA were obtained compared to the conventional MPA threshold (3.0 METs). Conversely, for VPA and SPA, lower, similar, or higher OATs were obtained depending on the METs derivation approach (OATsstandard or OATs60+) or the intensity categories (VO2max or VTs), compared to the conventional VPA threshold (6.0 METs). CONCLUSIONS: None of the derived OATs were concurrently similar to the CTs, suggesting that fitness-specific METs intensity thresholds adapted to the METs derivation approach should be used in older adults. TRIAL REGISTRATION: FenotipAGING (Non-health-care intervention study), PRO-Training (NCT05619250).

Frailty Influences the Relationship between the Soluble Receptor for Advanced Glycation-End Products and Mortality in Older Adults with Diabetes Mellitus.

INTRODUCTION: Frailty is prevalent among older adults with diabetes mellitus. Elevated serum levels of the soluble receptor for advanced glycation-end products (sRAGE) predict mortality in frail older adults. The evidence that sRAGE is also related to higher mortality in older adults with diabetes mellitus is inconsistent. Therefore, this study explored if frailty status influences the relationship between sRAGE and mortality in older adults with this condition. METHODS: We analysed data of 391 participants with diabetes mellitus (median age, 76 years) from four European cohorts enrolled in the FRAILOMIC project. Frailty was evaluated at baseline using Fried's criteria. Serum sRAGE was determined by ELISA. Participants were stratified by frailty status (n = 280 non-frail and 111 frail). Multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the relationship between sRAGE and mortality. RESULTS: During 6 years of follow-up, 98 participants died (46 non-frail and 52 frail). Non-survivors had significantly higher baseline levels of sRAGE than survivors (median [IQR]: 1,392 [962-2,043] pg/mL vs. 1,212 [963-1,514], p = 0.008). High serum sRAGE (>1,617 pg/mL) was associated with increased mortality in the whole diabetes sample after adjustment for relevant confounders (HR 2.06, 95% CI: 1.36-3.11, p < 0.001), and there was an interaction between sRAGE and frailty (p = 0.006). Accordingly, the association between sRAGE and mortality was stronger in the frail group compared to the non-frail group (HR 2.52, 95% CI: 1.30-4.90, p = 0.006 vs. HR 1.71, 95% CI: 0.91-3.23, p = 0.099, respectively). Likewise, Kaplan-Meier curves showed a significant difference in survival rates between frail participants with high sRAGE and those with low sRAGE (p = 0.001), whereas no survival difference was seen in the non-frail group (p = 0.09). CONCLUSIONS: Frailty status influences the relationship between sRAGE and mortality in older adults with diabetes mellitus. Determination of sRAGE in this population could be a useful tool for risk stratification.

Relationship of endogenous plasma concentrations of ß-hydroxy ß-methyl butyrate (HMB) with frailty in community dwelling older adults with type-2 diabetes mellitus.

BACKGROUND: Supplementation with ß-hydroxy ß-methyl butyrate (HMB) appears to be effective in preserving muscle in older adults. However, the association between endogenously produced HMB with frailty has not been studied in people with chronic disease. OBJECTIVES: The purpose of this study is to explore whether an association exists between endogenous HMB levels and frailty status in older adults with type-2 diabetes mellitus (T2DM). METHODS: Data were taken from the Toledo Study of Healthy Ageing, a community-dwelling aged (65 years+) cohort. Frailty was assessed at baseline and at 2.99 median years according to the Frailty Phenotype (FP) standardized to our population and the Frailty Trait Scale 12 (FTS12). The associations between HMB levels and frailty were assessed using three nested multivariate logistic regressions and segmented by sex. Glucose, HMB and glucose interaction, age and body composition were used as covariables. RESULTS: 255 participants (mean age 75.3 years, 52.94% men) were included. HMB levels showed an inverse cross-sectional association with frailty, which was modified when the interaction term HMB*glucose was included, remaining significant only for FTS12 [OR (95% CI): 0.436 (0.253, 0.751), p-value 0.003]. The association between HMB endogenous levels and FTS12 appears to be independent of sex, in which the association was maintained after adjusting for the covariates. However, there appears to be threshold points for glucose levels, above which the protective effect of HMB is lost: 145.4 mg/dl adjusted by gender for the whole sample and 149.6 mg/dl and 138.9 mg/dl for men and women, respectively. Endogenous HMB levels were not found to be associated with incident frailty. CONCLUSIONS: Cross-sectional analysis revealed that endogenous HMB levels were inversely associated with frailty as assessed by the FTS12 in older people with T2DM. This association was found to be dependent on circulating fasted glucose levels.

Power-oriented resistance training combined with high-intensity interval training in pre-frail and frail older people: comparison between traditional and cluster training set configurations on the force-velocity relationship, physical function and frailty.

OBJECTIVES: To analyse the force-velocity relationship changes in response to two different training programmes differing in the set configuration (cluster vs. traditional), and their impact on physical function and frailty in pre-frail and frail older adults. METHODS: 43 pre-frail and frail (Frailty Phenotype ≥ 1 criteria) older adults (81.4 ± 5.1 years) participated in this study. Participants were assigned to cluster (CT; n = 10; 10-s intra-set rest), traditional (TT; n = 13; no intra-set rest) or control (CON; n = 20) groups. Force-velocity relationship (F0, V0 and Pmax), physical function (Short Physical Performance Battery, SPPB) and frailty (Frailty Phenotype, FP) were assessed at baseline and after the training programme. RESULTS: Both CT and TT groups showed similar improvements in Pmax after training (CT = + 36.7 ± 34.2 W; TT = + 33.8 ± 44.6 W; both p < 0.01). V0 was improved by both CT (+ 0.08 ± 0.06 m s-1; p < 0.01), and TT (+ 0.07 ± 0.15 m s-1, p > 0.05). F0 remained unchanged in CT (+ 68.6 ± 224.2 N, p > 0.05) but increased in TT (+ 125.4 ± 226.8 N, p < 0.05). Finally, SPPB improved in both training conditions (CT = + 2.3 ± 1.3 points; TT = + 3.0 ± 1.2 points; both p < 0.05) and in the CON group (+ 0.9 ± 1.4 points, p < 0.05). CT and TT reduced their FP (CT = - 1.1 criteria; TT = - 1.6 criteria; both p < 0.01), while no changes were observed in the CON group (- 0.2 criteria, p = 0.38). CONCLUSIONS: Both training methods were equally effective for improving Pmax, physical function and reducing frailty in pre-frail and frail older people. TT may be effective for improving both force and velocity parameters, while CT may be effective for improving velocity parameters alone, although further research is required to confirm these findings.

Association between endogenous plasma beta-hydroxy-beta-methylbutyrate levels and frailty in community-dwelling older people.

BACKGROUND: Frailty is a key element in healthy ageing in which muscle performance plays a main role. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation has shown favourable effects in modulating protein synthesis, improving muscle mass and function in interventional studies. Decreased age-related endogenous HMB levels have been shown in previous studies. The aim of the present study is to assess whether there is an association between endogenous plasma HMB levels and frailty. METHODS: Data from 1290 subjects (56.98% women; mean ± standard deviation age 74.6 ± 5.95 years) from the Toledo Study for Healthy Aging were obtained. Participants had their frailty status qualified according to Fried's Frailty Phenotype (FFP) score and the Frailty Trait Scale in its 12-domain version (FTS-12). Plasma HMB levels were analysed by an ultrahigh-performance liquid chromatography tandem mass spectrometry. Differences between groups (frail vs. non-frail) were tested using Mann-Whitney U test, Kruskal-Wallis test and chi-squared test. The association between HMB and frailty was assessed by multivariate linear and logistic regressions when frailty was analysed as continuous and binary, respectively. Models were adjusted by age, gender, comorbidity, body composition and protein intake. RESULTS: HMB levels were lower in those aged ≥75 years than in those aged 65-74 years, with an inverse linear relationship between age and HMB levels (ß = -0.031; P = 0.018), mainly accounted by males (ß = -0.062; P = 0.002). HMB levels were higher in men (0.238 ± 0.065 vs. 0.193 ± 0.051 ng/mL; P ≤ 0.001). HMB levels were significantly lower in frail than in non-frail individuals: 0.204 ± 0.058 versus 0.217 ± 0.063 ng/dL (P = 0.001) according to the FFP and 0.203 ± 0.059 versus 0.219 ± 0.063 ng/mL (P < 0.001) according to FTS-12. These differences showed a dose-dependent profile when we compared them by quintiles of HMB (P for trend: 0.022; 0.012 and 0.0004, respectively, for FFP, FTS-12 binary and FTS-12 continuous). Variables associated with low HMB levels were body mass index, strength, exhaustion and weight loss. Frailty was associated with HMB levels in all the adjusted models, including the fully adjusted ones, no matter the tool used (odds ratio: 0.45 [0.26, 0.77] for FFP and 0.36 [0.20, 0.63] for FTS-12 binary; ß = -4.76 [-7.29, -2.23] for FTS-12 score). This association was also observed when the analyses were done by quintiles, showing such association since Q4 (FFP), Q2 (FTS-12 binary) and Q3 (FTS-12 score). The associations were observed in the whole sample and in each gender. CONCLUSIONS: There is an inverse association between HMB levels and frailty status. These findings support the design of targeted clinical trials to evaluate the effect of HMB supplementation in older frail people with low HMB levels.

Fat Mass Accounts for Insulin Resistance Impact on Functional Decline and Mortality in Nondiabetic Older Adults.

OBJECTIVE: To assess the potential role of body composition in the association of insulin resistance (IR) with functional decline and mortality in nondiabetic older persons. DESIGN: Longitudinal population-based cohort of community-dwelling people from Toledo, Spain, aged 65 years or older. SETTING AND PARTICIPANTS: A total of 1114 nondiabetic persons from the Toledo Study of Healthy Aging cohort (mean age: 74.5, 56.10% female) with complete data at baseline were included. Only 914 participants had fully assessment of functional evaluation during the follow-up period. METHODS: IR was determined by the homeostasis model assessment index (HOMA-IR) at baseline while frailty was assessed by the Frailty Trait Scale-5 (FTS-5) at baseline and after 2.99 years' median follow-up period. A total of 319 participants experienced functional decline (2.5-point reduction in the FTS-5 score). A total of 143 deaths were recorded (6.31 years median follow-up) from the Spanish National Death Index. Body compositions were determined using dual-energy x-ray absorptiometry. Multivariate regression models analyzed the effect of HOMA-IR on outcomes, with age, sex, Charlson index, and number of medications included in the basic adjustment model. RESULTS: A 1-logaritmic unit increment in HOMA-IR increased the risk of functional decline after basic adjustment [odds ratio (95% confidence interval): 1.41 (1.09-1.83), P = .009]. This significant association was lost when further adjusted for total fat mass [1.14 (0.86-1.50)] and trunk fat mass [1.03 (0.77-1.37)], which accounted for 62.92% and 91.49% of the association. HOMA-IR was inversely associated with mortality risk [hazard ratio 0.66 (0.49-0.87), P = .0037], an association lost after adjustment for total fat mass [0.74 (0.55-1.01)] and trunk fat mass [0.80 (0.58-1.09)], accounting for 29.05% and 45.78% of the association. Adjustment by lean mass did not modify any of the associations. CONCLUSIONS AND IMPLICATIONS: Body fat mass, especially in the trunk region, mediates the association of IR with functional decline and to a lesser extent with reduced risk of mortality in nondiabetic older subjects.

Optimization of VO2 and VCO2 outputs for the calculation of resting metabolic rate using a portable indirect calorimeter.

This study aimed to compare the Cosmed K5 portable indirect calorimeter, using the mixing chamber mode and face mask, with a stationary metabolic cart when measuring the resting metabolic rate (RMR) and to derive fitting equations if discrepancies are observed. Forty-three adults (18-84 years) were assessed for their RMR for two 30-min consecutive and counterbalanced periods using a Cosmed K5 and an Oxycon Pro. Differences among devices were tested using paired sample Student's t-tests, and correlation and agreement were assessed using Pearson's correlation coefficients, intraclass correlation coefficient and Bland-Altman plots. Forward stepwise multiple linear regression models were performed to develop fitting equations for estimating differences among devices when assessing oxygen uptake (VO2 diff , mL·min-1 ) and carbon dioxide production (VCO2 diff , mL·min-1 ). Furthermore, the Oxycon Pro was tested before being confirmed as a reference device. Significant differences between devices were found in most metabolic and ventilatory parameters, including the primary outcomes of VO2 and VCO2 . These differences showed an overestimation of the Cosmed K5 in all metabolic outcomes, except for Fat, when compared to the Oxycon Pro. When derived fitting equations were applied (VO2 diff - 139.210 + 0.786 [weight, kg] + 1.761 [height, cm] - 0.941 [Cosmed K5 VO2 , mL·min-1 ]; VCO2 diff - 86.569 + 0.548 [weight, kg] + 0.915 [height, cm] - 0.728 [Cosmed K5 VCO2 , mL·min-1 ]), differences were minimized, and agreement was maximized. This study provides fitting equations which allow the use of the Cosmed K5 for reasonably optimal RMR determinations.

Predictors of Maintained Transitions Between Robustness and Prefrailty in Community-Dwelling Older Spaniards.

OBJECTIVES: We aimed to explore predictors of sustained transitions (those that are maintained for an extra follow-up) between robustness and prefrailty in both directions. DESIGN: Longitudinal population-based cohort. SETTING AND PARTICIPANTS: Community-dwelling Spaniards 65 years or older from the Toledo Study of Healthy Ageing. METHODS: The Fried's frailty phenotype was measured over 3 waves (2006-2009, 2011-2013, and 2014-2017). Multiple logistic regressions compared individuals following the pattern robust-prefrail-prefrail with those who remained robust across waves, and those following the pattern prefrail-robust-robust with those who remained prefrail, for sociodemographic, clinical, life-habits, dependency for activities of daily living, upper and lower extremities' strength variables. The Fried's items of those who remained prefrail and those who became robust were compared. RESULTS: Mean age was 72.3 years (95% CI: 71.8-72.8) and 57.9% (52.7%-63.0%) were women. After multivariate adjustment, predictors (apart from age) of the sustained transition robustness-prefrailty were as follows: number of drugs taken (odds ratio: 1.37; 95% CI: 1.14-1.65), not declaring the amount of alcohol consumed (8.32; 1.78-38.88), and grip strength (0.92 per kg; 0.86-0.99). Predictors of the sustained transition prefrailty-robustness were as follows: drinking alcohol (0.2; 0.05-0.83), uricemia (0.67; 0.49-0.93), number of chair stands in 30 seconds (1.14; 1.01-1.28), and grip strength (1.12; 1.05-1.2). Low grip strength was associated with a lower probability of regaining robustness. CONCLUSIONS AND IMPLICATIONS: Prediction of sustained transitions between the first stages of frailty development can be achieved with a reduced number of variables and noting whether the Fried's item leading to a diagnosis of prefrailty is low grip strength. Our results suggest the need to intensify interventions on deprescription, quitting alcohol, and strengthening of upper and lower limbs.

Physical performance measures in frailty screening: diagnostic and prognostic accuracy in the Toledo Study of Healthy Ageing.

INTRODUCTION: The present study aimed to explore the diagnostic and prognostic accuracy of standard and population-specific Physical Performance Measures (PPMs) cut-off points for frailty screening. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Population-based study including 2328 subjects from the Toledo Study of Healthy Aging (age = 76.37 ± 6.78). Data related to frailty status and PPMs was collected at baseline visit (2011-2013). Mortality and hospitalization were ascertained up to March 2019 and December 2017, respectively, whereas disability onset and worsening were evaluated in the 2015-2017 visit. METHODS: Gait speed and Short Physical Performance Battery population-specific cut-off points for frailty were computed using receiver operating characteristics (ROC) curve analysis. Head-to-head comparison of associations with adverse events against existing reference values (SPPB≤6, GS < 0.8 m/s) and classical (Frailty Phenotype, Frailty Index) and newly incorporated frailty tools (12- and 5-item Frailty Trait Scale) were explored through logistic and Cox regressions. Predictive ability was compared through areas under the curves (AUCs) for disability onset/worsening and integrated AUCs for mortality and hospitalization (time-censoring adverse events). RESULTS: PPMs population-specific cut-off points (SPPB ≤7 and GS ≤ 0.75 m/s for males; SPPB ≤4 and GS ≤ 0.5 for females) outperformed published reference thresholds in terms of diagnostic accuracy. Frailty identified through PPMs was associated with adverse events (death, hospitalization and incident disability) similarly to that assessed using the newly incorporated tools and showed similar prognostic accuracy (mortality [IAUCs≈0.7], hospitalization [IAUCs≈0.8] and disability onset/worsening [AUCs≈0.62]), except for the tool used to assess frailty. CONCLUSIONS: Our results suggest that PPMs might serve as the first screen to identify candidates for further frailty assessment and exploration of underlying mechanisms, allowing opportunistic on-time screening in different settings (community and primary care) in which frailty instruments are rarely implementable.

Differential Association of Frailty and Sarcopenia With Mortality and Disability: Insight Supporting Clinical Subtypes of Frailty.

OBJECTIVES: Sarcopenia and frailty have been shown separately to predict disability and death in old age. Our aim was to determine if sarcopenia may modify the prognosis of frailty regarding both mortality and disability, raising the existence of clinical subtypes of frailty depending on the presence of sarcopenia. DESIGN: A Spanish longitudinal population-based study. SETTING AND PARTICIPANTS: The population consists of 1531 participants (>65 years of age) from the Toledo Study of Health Aging. METHODS: Sarcopenia and frailty were assessed following Foundation for the National Institutes of Health criteria and the Fried Frailty Phenotype, respectively. Mortality was assessed using the National Death Index. Functional status was determined using Katz index. We ran multivariate logistics and proportional hazards models adjusting for age, sex, baseline function, and comorbidities. RESULTS: Mean age was 75.4 years (SD 5.9). Overall, 70 participants were frail (4.6%), 565 prefrail (36.9%), and 435 sarcopenic (28.4%). Mean follow-up was 5.5 and 3.0 years for death and worsening function, respectively. Furthermore, 184 participants died (12%) and 324 worsened their functioning (24.8%). Frailty and prefrailty were associated with mortality and remained significant after adjustment by sarcopenia [hazard risk (HR) 3.09, 95% confidence interval (CI) 1.84-5.18; P < .001; HR 1.58, 95% CI 1.12-2.24, P = .01]. However, the association of sarcopenia with mortality was reduced and became nonsignificant (HR 1.43, 95% CI 0.99-2.07, P = .057) when both frailty and sarcopenia were included in the same model. In the disability model, frailty and sarcopenia showed a statistically significant interaction (P = .016): both had to be present to predict worsening of disability. CONCLUSIONS AND IMPLICATIONS: Sarcopenia plays a relevant role in the increased risk of functional impairment associated to frailty, but that seems not to be the case with mortality. This finding raises the need of assessing sarcopenia as a cornerstone of the clinical work after diagnosing frailty.

Transitions Between Frailty States and Its Predictors in a Cohort of Community-Dwelling Spaniards.

OBJECTIVES: Study the frequency and determinants of frailty transitions in a community-dwelling older population. DESIGN: Population-based prospective longitudinal study [The Toledo Study of Healthy Ageing (TSHA)]. SETTING AND PARTICIPANTS: 1748 community-dwelling individuals aged >65 years living in Toledo, a Spanish province. METHODS: Frailty was measured with the Fried phenotype. Logistic models were used to assess the associations of sociodemographic, clinical, life-habits, functional, physical performance, and analytical variables with frailty transitions (losing robustness, transitioning from prefrailty to robustness, and from prefrailty to frailty) over a median of 5.2 years. RESULTS: Mean age on enrolment was 75 years, and 55.8% were females. At baseline, 10.3% were frail and 43.1% prefrail. At follow-up, 35.8% of the frail individuals recovered to a prefrail and 15.1% to a robust state. In addition, 43.7% of the prefrail participants became robust, but 14.5% developed frailty. Of those robust at baseline, 32.9% became prefrail and 4.2% frail. In multivariate logistic models, chair-stands had a predictive role in all transitions studied: linearly in keeping robustness and with a floor effect (5 stands) in transitions from prefrailty to robustness and (inversely) from prefrailty to frailty. More depressive symptoms were associated with unfavorable transitions. Not declaring the amount of alcohol drunk and low grip strength were associated with loss of robustness. Hearing and cognitive impairment, low physical activity and smoking with transitioning from prefrailty to frailty. Autonomy for instrumental activities of daily living and uricemia were associated with transitions between robustness and prefrailty in both directions. Increasing body mass index in the range of moderate to severe obesity hampered regaining robustness. CONCLUSIONS AND IMPLICATIONS: Spontaneous improvement of frailty measured with the Fried phenotype is frequent, mainly to prefrailty. Most of the variables associated with transitions are modifiable and suggest research topics and interventions to reduce frailty in clinical and social care settings.

Impact of Relative Muscle Power on Hospitalization and All-Cause Mortality in Older Adults.

BACKGROUND: The purpose of this study was to evaluate the relationship of lower-limb muscle power with mortality and hospitalization. METHODS: A total of 1 928 participants from the Toledo Study for Healthy Aging were included. Muscle power was assessed with the 5-repetition sit-to-stand test and participants were classified into different groups of relative power (ie, normalized to body mass) according to sex-specific tertiles and their inability to perform the test. Mean follow-up periods for hospitalization and all-cause mortality were 3.3 and 6.3 years, respectively. RESULTS: Compared to the high relative muscle power group, men with low (HR [95% CI] = 2.1 [1.2-3.6]) and women with very low and low (HR [95% CI] = 4.7 [3.0-7.4] and 1.8 [1.2-2.7]) relative power had an increased age-adjusted risk of hospitalization. After adjusting for several covariates (age, physical activity, body mass index education, depression, comorbidities, disability, and handgrip strength), these effects were attenuated (men and women with very low relative power: HR [95% CI] = 1.6 [0.9-2.9] and 2.8 [1.6-4.9]). The very low relative muscle power group had also an increased all-cause mortality risk (age-adjusted) in both men and women (HR [95% CI] = 2.3 [1.4-3.9] and 2.9 [1.6-5.3]). After adjusting for all the covariates, a significantly increased mortality risk was observed only in men (HR [95% CI] = 2.1 [1.1-3.8]; women HR [95% CI] = 1.6 [0.8-3.2]), with very low levels of relative power. CONCLUSIONS: Relative muscle power was independently and negatively associated with mortality and hospitalization in older adults. An augmented all-cause mortality risk was noted in the lowest group of relative muscle power.

Changes in Health Behaviors, Mental and Physical Health among Older Adults under Severe Lockdown Restrictions during the COVID-19 Pandemic in Spain.

We used data from 3041 participants in four cohorts of community-dwelling individuals aged ≥65 years in Spain collected through a pre-pandemic face-to-face interview and a telephone interview conducted between weeks 7 to 15 after the beginning of the COVID-19 lockdown. On average, the confinement was not associated with a deterioration in lifestyle risk factors (smoking, alcohol intake, diet, or weight), except for a decreased physical activity and increased sedentary time, which reversed with the end of confinement. However, chronic pain worsened, and moderate declines in mental health, that did not seem to reverse after restrictions were lifted, were observed. Males, older adults with greater social isolation or greater feelings of loneliness, those with poorer housing conditions, as well as those with a higher prevalence of chronic morbidities were at increased risk of developing unhealthier lifestyles or mental health declines with confinement. On the other hand, previously having a greater adherence to the Mediterranean diet and doing more physical activity protected older adults from developing unhealthier lifestyles with confinement. If another lockdown were imposed during this or future pandemics, public health programs should specially address the needs of older individuals with male sex, greater social isolation, sub-optimal housing conditions, and chronic morbidities because of their greater vulnerability to the enacted movement restrictions.

New Insights on the Conversion Reaction Mechanism in Metal Oxide Electrodes for Sodium-Ion Batteries.

Due to the abundance and low cost of exchanged metal, sodium-ion batteries have attracted increasing research attention for the massive energy storage associated with renewable energy sources. Nickel oxide (NiO) thin films have been prepared by magnetron sputtering (MS) deposition under an oblique angle configuration (OAD) and used as electrodes for Na-ion batteries. A systematic chemical, structural and electrochemical analysis of this electrode has been carried out. The electrochemical characterization by galvanostatic charge-discharge cycling and cyclic voltammetry has revealed a certain loss of performance after the initial cycling of the battery. The conversion reaction of NiO with sodium ions during the discharge process to generate sodium oxide and Ni metal has been confirmed by X-ray photoelectron spectra (XPS) and micro-Raman analysis. Likewise, it has been determined that the charging process is not totally reversible, causing a reduction in battery capacity.

A robust machine learning framework to identify signatures for frailty: a nested case-control study in four aging European cohorts.

Phenotype-specific omic expression patterns in people with frailty could provide invaluable insight into the underlying multi-systemic pathological processes and targets for intervention. Classical approaches to frailty have not considered the potential for different frailty phenotypes. We characterized associations between frailty (with/without disability) and sets of omic factors (genomic, proteomic, and metabolomic) plus markers measured in routine geriatric care. This study was a prevalent case control using stored biospecimens (urine, whole blood, cells, plasma, and serum) from 1522 individuals (identified as robust (R), pre-frail (P), or frail (F)] from the Toledo Study of Healthy Aging (R=178/P=184/F=109), 3 City Bordeaux (111/269/100), Aging Multidisciplinary Investigation (157/79/54) and InCHIANTI (106/98/77) cohorts. The analysis included over 35,000 omic and routine laboratory variables from robust and frail or pre-frail (with/without disability) individuals using a machine learning framework. We identified three protective biomarkers, vitamin D3 (OR: 0.81 [95% CI: 0.68-0.98]), lutein zeaxanthin (OR: 0.82 [95% CI: 0.70-0.97]), and miRNA125b-5p (OR: 0.73, [95% CI: 0.56-0.97]) and one risk biomarker, cardiac troponin T (OR: 1.25 [95% CI: 1.23-1.27]). Excluding individuals with a disability, one protective biomarker was identified, miR125b-5p (OR: 0.85, [95% CI: 0.81-0.88]). Three risks of frailty biomarkers were detected: pro-BNP (OR: 1.47 [95% CI: 1.27-1.7]), cardiac troponin T (OR: 1.29 [95% CI: 1.21-1.38]), and sRAGE (OR: 1.26 [95% CI: 1.01-1.57]). Three key frailty biomarkers demonstrated a statistical association with frailty (oxidative stress, vitamin D, and cardiovascular system) with relationship patterns differing depending on the presence or absence of a disability.