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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/m 2 ; 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); β(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.

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., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Supplementation with β-hydroxy β-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., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

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., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

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 (β = -0.031; P = 0.018), mainly accounted by males (β = -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; β = -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., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

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 (F 0 , V 0 and P max ), 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 P max after training (CT =  + 36.7 ± 34.2 W; TT =  + 33.8 ± 44.6 W; both p < 0.01). V 0 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). F 0 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 P max , 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., (© 2023. The Author(s).)

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., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

High-sensitivity C-reactive protein (hsCRP) and homocysteine (Hcy) are inflammation markers but are also related to cardiovascular diseases, disability, or higher risk of death. Although inflammation is considered to be associated with frailty, data regarding the association between hsCRP or Hcy and frailty are controversial or scarce, especially with respect to their association with prefrailty. Thus, our objective was to study the association of hsCRP and Hcy with prefrailty and frailty in 1,211 Spanish men and women aged 65-98 years from the Toledo Study for Healthy Aging (TSHA) cohort, classified according to Fried's criteria. Hcy was independently associated with frailty (odds ratio [OR] = 1.06; 95% confidence interval [CI]: 1.01-1.12), whereas hsCRP was independently associated with both prefrailty (OR = 1.03; 95% CI: 1.01-1.06) and frailty (OR = 1.07; 95% CI: 1.02-1.12). Furthermore, both markers were positively correlated with the number of Fried's criteria that were met and were independently associated with the criteria of exhaustion (Hcy: OR = 1.03, 95% CI: 1.00-1.06), weakness (hsCRP: OR = 1.03, 95% CI: 1.01-1.05), and low physical activity (hsCRP: OR = 1.04, 95% CI: 1.02-1.06). Thus, our results highlight the importance of inflammation in age-related physical decline and, in particular, its association with fatigue, low strength, and decreased physical activity., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: A poor fat-soluble micronutrient (FMN) and a high oxidative stress status are associated with frailty. Our aim was to determine the cross-sectional association of FMNs and oxidative stress biomarkers [protein carbonyls (PrCarb) and 3-nitrotyrosine] with the frailty status in participants older than 65 years., Methods: Plasma levels of vitamins A (retinol), D 3 , E (α-tocopherol and γ-tocopherol) and carotenoids (α-carotene and β-carotene, lycopene, lutein/zeaxanthin, and β-cryptoxanthin), PrCarb, and 3-nitrotyrosine were measured in 1450 individuals of the FRAILOMIC initiative. Participants were classified into robust, pre-frail, and frail using Fried's frailty criteria. Associations between biomarkers and frailty status were assessed by general linear and logistic regression models, both adjusted for cohort, season of blood sampling, gender, age, height, weight, and smoking., Results: Robust participants had significantly higher vitamin D 3 and lutein/zeaxanthin concentrations than pre-frail and frail subjects; had significantly higher γ-tocopherol, α-carotene, β-carotene, lycopene, and β-cryptoxanthin concentrations than frail subjects, and had significantly lower PrCarb concentrations than frail participants in multivariate linear models. Frail subjects were more likely to be in the lowest than in the highest tertile for vitamin D 3 (adjusted odds ratio: 2.15; 95% confidence interval: 1.42-3.26), α-tocopherol (2.12; 1.39-3.24), α-carotene (1.69; 1.00-2.88), β-carotene (1.84; 1.13-2.99), lycopene (1.94; 1.24-3.05), lutein/zeaxanthin (3.60; 2.34-5.53), and β-cryptoxanthin (3.02; 1.95-4.69) and were more likely to be in the highest than in the lowest tertile for PrCarb (2.86; 1.82-4.49) than robust subjects in multivariate regression models., Conclusions: Our study indicates that both low FMN and high PrCarb concentrations are associated with pre-frailty and frailty., (© 2019 The Authors Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Increasing life expectancy results in more elderly people struggling with age related diseases and functional conditions. This poses huge challenges towards establishing new approaches for maintaining health at a higher age. An important aspect for age related deterioration of the general patient condition is frailty. The frailty syndrome is associated with a high risk for falls, hospitalization, disability, and finally increased mortality. Using predictive data mining enables the discovery of potential risk factors and can be used as clinical decision support system, which provides the medical doctor with information on the probable clinical patient outcome. This enables the professional to react promptly and to avert likely adverse events in advance., Methods: Medical data of 474 study participants containing 284 health related parameters, including questionnaire answers, blood parameters and vital parameters from the Toledo Study for Healthy Aging (TSHA) was used. Binary classification models were built in order to distinguish between frail and non-frail study subjects., Results: Using the available TSHA data and the discovered potential predictors, it was possible to design, develop and evaluate a variety of different predictive models for the frailty syndrome. The best performing model was the support vector machine (SVM, 78.31%). Moreover, a methodology was developed, making it possible to explore and to use incomplete medical data and further identify potential predictors and enable interpretability., Conclusions: This work demonstrates that it is feasible to use incomplete, imbalanced medical data for the development of a predictive model for the frailty syndrome. Moreover, potential predictive factors have been discovered, which were clinically approved by the clinicians. Future work will improve prediction accuracy, especially with regard to separating the group of frail patients into frail and pre-frail ones and analyze the differences among them.

Background: Homocysteine (Hcy) high levels are associated with fractures, bone resorption and an early onset of osteoporosis in elderly persons; a relationship between Hcy and bone formation has also been suggested but is still controversial. Frailty, an independent predictor of fractures and decreased bone mineral density is associated with altered bone metabolism in women. However, no previous works have studied the relationship among frailty, Hcy levels and bone turnover., Methods: We studied the association among Hcy, osteoporosis and N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (β-CTX), parathyroid hormone (PTH), calcium and 25-hydroxyvitamin D (25(OH)D) in 631 Spanish women between the ages of 65-78 from the Toledo Study for Healthy Aging (TSHA) cohort, who were classified as highly functional (robust subjects) or non-robust (pre-frail or frail subjects) according to Fried's criteria., Results: Hcy was independently associated with β-CTX in the entire population (B = 0.22; 95% CI, 0.09-0.34; p = 0.001) and in the non-robust group (B = 0.24; 95% CI, 0.09-0.39; p = 0.002). Hcy was also associated with PINP in the entire and non-robust populations, but the association was lost after including the levels of β-CTX, but not the other bone biomarkers, in the multivariate analysis. This suggests that the controversial relationship between Hcy and bone formation might be explained, at least to a certain extent, by the confounding effects of β-CTX., Conclusions: This work highlights the important implication of frailty status in the association between Hcy and increased bone turnover in older women., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: The search for biomarkers that can lead to the early diagnosis and thus, early treatment of frailty, has become one of the main challenges facing the geriatric scientific community. The aim of the present study was to identify single nucleotide polymorphisms (SNPs) related to frailty., Material and Methods: The study was conducted on 152 subjects from the Toledo Study for Healthy Aging (65 to 95 years of age), and classified as frail (n=78), and non-frail (n=74), according to Fried's criteria. After blood collection, DNA was isolated and amplified for the analysis of SNPs using Axiom TM Genotyping technology (Affymetrix). Statistical analyses were performed using the Plink program and library SNPassoc., Results: The results of the study showed 15 SNPs with a P<.001. Those SNPs involved in processes related to frailty, such as energy metabolism, regulation of biological processes, cell motility and integrity, and cognition are highlighted., Conclusions: These results suggest that the genetic variations identified in frail individuals that are involved in biological processes related to frailty may be considered as biomarkers for the early detection of frailty., (Copyright © 2018 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Sedentary behaviour (SB) has recently emerged as an independent risk factor for different health outcomes. Older adults accumulate long time in SB. Understanding the role that SB plays on health is crucial for a successful aging. This short systematic review summarizes the current evidence related to the effects of objectively measured SB on frailty, physical performance and mortality in adults ≥60 years old. The literature search produced 271 records for physical performance (n = 119), frailty (n = 31), and mortality (n = 121). Finally, only 13 articles fulfilled the inclusion criteria and were included in this review. All articles but one included in the physical performance section (n = 9) showed a negative association between longer time spent in SB and physical performance. A significant association of SB with higher odds of frailty was found, however this association disappeared after adjusting for cognitive status. Lastly, two of the three included studies showed positive associations between SB and mortality, but this effect decreased or even disappeared in the more adjusted models. In conclusion, there is consistency that SB is negatively associated with physical performance. However, the relationship between objectively measured SB and frailty incidence and mortality rates remains unclear and deserves further research. The use of homogenous criteria to assess SB and the inclusion of more robust research designs will help clarifying the independent effects that SB could have on physical performance, frailty, and mortality. This will ultimately help designing more efficient and comprehensive physical activity guidelines for older adults.

Background: Specific mechanisms underlying frailty syndrome are not well known. Frailty can be viewed as a loss of functional reserve resulting in increased vulnerability to stressors. We hypothesize that pathways regulating cellular response to stress are potential players in the development of frailty. The aim of this study was to evaluate the association of the expression of certain genes related to cellular response to stress with the presence of frailty in older patients., Methods: A sample of 350 individuals aged 65 years or older (22% frail) was selected from the Toledo Study of Healthy Aging. RNA was extracted from blood and retro-transcribed into complementary DNA. TaqMan Low density Arrays were used for the measurement of expression of genes implicated in cellular response to oxidative stress, genes implicated in inflammation, genes implicated in vascular physiology, and genes related to hypoxia. For data analysis, a logistic regression model was used to assess the relationship of gene expression and frailty., Results: Among the analyzed genes, lower expression of genes related to cellular response to hypoxia (hypoxia inducible factor-1α) or to cellular response to oxidative stress (nuclear factor erythroid 2-related factor 2 and its target genes heme oxygenase-2, thioredoxin reductase-1, and superoxide dismutase-2), but not to those related to inflammation or vascular physiology, were significantly associated with the presence of frailty after adjustment for age and sex. These associations remained significant after adjustment by type 2 diabetes and Charlson index of comorbidities. Lower expressions of genes involved in cellular response to stress were also associated with increased risk of functional impairment., Conclusions: Reduced expression of several genes implicated in cellular response to oxidative stress or hypoxia is significantly associated with the presence of frailty. These results help to fill the gap of knowledge of this evolving field and provide targets for intervention to promote health and independence in the elderly., (Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The expression of certain genes involved in response to oxidative stress is likely related to aging-related outcomes, such as frailty in old age. Given nutrition's substantial impact in aging and age-related diseases, one of its mechanisms might be through influencing gene expression.Objective: This study aimed to investigate the association between nutrition and the expression of 15 genes related to cellular response to stress in older community-dwelling individuals.Methods: A nested case-control study of 350 participants (mean ± SEM age: 76.5 ± 6.9 y, 42.9% men, 22% frail according to Fried's criteria) was selected from the Toledo Study for Healthy Aging. Blood-derived RNA was retro-transcribed into complementary DNA. TaqMan Arrays were used for determining gene expression. The Mini Nutritional Assessment (MNA) and the PREDIMED (PREvención con DIeta MEDiterranea) questionnaire measured nutritional status and adherence to the Mediterranean diet (MD), respectively. Data were reweighed so that inference from linear and logistic regression models applied to the original sampling population.Results: Higher MNA scores were associated with higher expressions of the gene coding for sirtuin-1 (SIRT1), regardless of age, sex, and Charlson comorbidity score (P = 0.04) and even after adjusting for frailty status (P = 0.016) and level of adherence to the MD (P = 0.04). Malnutrition risk and SIRT1 gene expression were inversely associated (P = 0.0045) independently of frailty status (P = 0.0045) and level of adherence to the MD (P = 0.0075).Conclusions: In older individuals, improvement in nutritional status is positively associated with SIRT1 gene expression independently of frailty status or adherence to the MD. These findings may provide potential biomarkers and targets for health interventions among the elderly. [ABSTRACT FROM AUTHOR]

Background: Physical frailty has become the center of attention of basic, clinical and demographic research due to its incidence level and gravity of adverse outcomes with age. Frailty syndrome is estimated to affect 20 % of the population older than 75 years. Thus, one of the greatest current challenges in this field is to identify parameters that can discriminate between vulnerable and robust subjects. Gait analysis has been widely used to predict frailty. The aim of the present study was to investigate whether a collection of parameters extracted from the trunk acceleration signals could provide additional accurate information about frailty syndrome. Methods: A total of 718 subjects from an elderly population (319 males, 399 females; age: 75.4 ± 6.1 years, mass: 71.8 ± 12.4 kg, height: 158 ± 6 cm) volunteered to participate in this study. The subjects completed a 3-m walk test at their own gait velocity. Kinematic data were acquired from a tri-axial inertial orientation tracker. Findings: The spatio-temporal and frequency parameters measured in this study with an inertial sensor are related to gait disorders and showed significant differences among groups (frail, pre-frail and robust). A selection of those parameters improves frailty classification obtained to gait velocity, compared to classification model based on gait velocity solely. Interpretation: Gait parameters simultaneously used with gait velocity are able to provide useful information for a more accurate frailty classification. Moreover, this technique could improve the early detection of pre-frail status, allowing clinicians to perform measurements outside of a laboratory environment with the potential to prescribe a treatment for reversing their physical decline. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To provide a new instrument to diagnose frailty, the Frailty Trait Scale (FTS), that allows a more precise assessment and monitoring of individuals. Design: Prospective population-based cohort study. Setting: The Toledo Study for Healthy Aging, Spain. Participants: A total of 1972 men and women aged 65 years or older. Measurements: We identified 7 frailty dimensions (energy balance–nutrition, physical activity, nervous system, vascular system, strength, endurance, and gait speed) represented by 12 items. Each item was pondered based on the quintiles of its distribution in the study population. Validity was evaluated by testing its association with factors related to frailty and its predictive value for adverse events. This predictive capacity was further compared with the capacity of 2 well-established frailty models (the frailty phenotype and the Frailty Index). Results: FTS score was associated with several comorbidities and biomarkers classically associated with frailty. The FTS was associated with the incidence of hospitalization and mortality (hazard ratio associated with a score in the highest quartile [versus the first quartile] = 2.3, 95% confidence interval [CI] 1.6–3.4, and 2.5, 95% CI 1.8–3.6, respectively). Compared with Fried et al's definition, the FTS showed a better predictor for hospitalization in persons younger than 80 (area under the curve [AUC] = 0.65 vs 0.62, P = .01), and for mortality in the oldest group (AUC = 0.77 vs 0.72, P = .02). FTS showed similar predictive value to the Frailty Index. Conclusion: FTS associates with many of the factors linked to frailty and has a similar predictive capacity to that provided by the classical instruments. Its characteristics offer some advantages over them, with potential utility in research and clinical practice. [Copyright &y& Elsevier]

Introduction Frailty is a strong predictor of adverse health events, but its impact on cognitive function is poorly understood. Aim To assess cognitive performance in frailty and to identify the frailty stage where cognitive impairment begins. Methods Data were taken from 2044 people aged ≥65 years without cognitive impairment selected from the Toledo Study for Healthy Aging, a population-based cohort of older adults. Frailty status was assessed by 3 different scales: Frailty Phenotype (FP), Frailty Trait Scale (FTS), and Frailty Index (FI). Neuropsychological assessments of different cognitive domains included the Mini-Mental State Examination, Short and Long-Term Memory Recalling Test, the Boston Naming Test, Verbal Fluency Test, Digit Span Forward, Go/No-go Test, Luria Orders Test, Clock Drawing Test, and Serial Word Learning Test. The relationships between the score of the scales and frailty status (robust, prefrail, and frail for FP and quartiles for FTS and FI) were analyzed using multivariate linear regression models including age, sex, and educative level as possible confounders. Results Participants classified as the worst degree of frailty (frail in FP and fourth quartile of FTS and FI) presented more cognitive domains affected and to a higher extent than moderate frail (prefrail and second quartile and third quartile of FTS and FI) and robust (and first quartile of FTS and FI) participants. Conclusions Cognitive performance progressively declined across the frailty state, regardless of the instrument used to assess frailty. In prefrail participants, cognitive impairment may be an early marker of frailty-dependent cerebral involvement and could be already subject to interventions aimed at reducing the transition to frailty. [ABSTRACT FROM AUTHOR]

Objectives To evaluate for the first time the longitudinal relationship between serum uric acid concentrations and risk of frailty. Methods Prospective cohort study of 2198 non-institutionalized individuals aged ≥ 60 years recruited in 2008–2010. At baseline, information was obtained on socio-demographic factors, health behaviors and morbidity, while serum uric acid was determined in 12-h fasting blood samples. Study participants were followed-up through 2012 to assess incident frailty, defined as ≥ 2 of the following 4 Fried criteria: exhaustion, muscle weakness, low physical activity, and slow walking speed. Results During a mean 3.5-year follow-up, 256 cases of incident frailty were identified. After multivariate adjustment, the odds ratios (95% confidence interval) of frailty comparing the second and third tertiles of uric acid to the lowest tertile were, respectively: 1.18 (0.83–1.68) and 1.57 (1.11–2.22); p-linear trend = 0.01. The corresponding result for a 1 mg/dL increase in serum uric acid concentration was 1.12 (1.00–1.24). Similar associations were observed across subgroups defined by sex, age, body mass index, and physical activity. As regards each frailty component, the odds ratios (95% confidence interval) per 1 mg/dL increase in serum uric acid were 1.10 (0.99–1.23) for low physical activity, 1.08 (0.95–1.23) for low walking speed, 1.08 (0.67–1.73) for exhaustion and 0.91 (0.81–1.02) for weakness. Conclusions Serum uric acid concentrations are positively associated with the risk of frailty in older adults. Further studies are needed to evaluate whether specific dietary recommendations or pharmacological strategies aimed at lowering serum uric acid would be beneficial to prevent the development of this syndrome. [ABSTRACT FROM AUTHOR]