Response rates and associated factors after a multicomponent intervention in frail older adults with diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and frailty are associated with functional decline in older population. OBJECTIVE: To explore the individual response to a multimodal intervention on functional performance. DESIGN: A cluster-randomised multicentre clinical trial. SETTING: Outpatients in hospital or primary care. SUBJECTS: 843 (77.83 years, 50.65% men) prefrail and frail individuals ≥70 years with T2DM. METHODS: Participants were allocated to usual care group (UCG) or a multicomponent intervention group (IG): 16-week progressive resistance training, seven nutritional and diabetological educational sessions and achievement of glycated haemoglobin (7-8%) and blood pressure (<150 mmHg) targets. Functional performance was assessed with the Short Physical Performance Battery (SPPB) at 1 year. We used multivariate binomial and multinomial logistic regression models to explore the effect of the IG, and adherence on the outcomes studied, in several adjusted models. RESULTS: 53.7% in the IG versus 38.0% in the UCG improved by at least 1 point in their SPPB score [OR (95% CI): 2.07 (1.43, 2.98), P value <0.001]. Age, SPPB score and number of frailty criteria met decreased the probability of improving the SPPB score. Factors associated with worsening were pertaining to IG (decreased), age, SPPB score and the number of frailty criteria (increased). An adherence ≥84% was needed to achieve benefits, reaching the peak in the probability of improving SPPB when this was ≥85% [OR(95%CI): 2.38 (1.29, 4.79), P value 0.014]. CONCLUSIONS: Factors predicting the likelihood of improvement in a multimodal programme in pre-frail and frail older adults with diabetes are age, basal SPPB score, the number of frailty criteria and adherence.

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.

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.

Differential utility of various frailty diagnostic tools in non-geriatric hospital departments of several countries: A longitudinal study.

BACKGROUND: There is limited knowledge on the performance of different frailty scales in clinical settings. We sought to evaluate in non-geriatric hospital departments the feasibility, agreement and predictive ability for adverse events after 1 year follow-up of several frailty assessment tools. METHODS: Longitudinal study with 667 older adults recruited from five hospitals in three different countries (Spain, Italy and United Kingdom). Participants were older than 75 years attending the emergency room, cardiology and surgery departments. Frailty scales used were Frailty Phenotype (FP), FRAIL scale, Tilburg and Groningen Frailty Indicators, and Clinical Frailty Scale (CFS). Analyses included the prevalence of frailty, degree of agreement between tools, feasibility and prognostic value for hospital readmission, worsening of disability and mortality, by tool and setting. RESULTS: Emergency Room and cardiology were the settings with the highest frailty prevalence, varying by tool between 40.4% and 67.2%; elective surgery was the one with the lowest prevalence (between 13.2% and 38.2%). The tools showed a fair to moderate agreement. FP showed the lowest feasibility, especially in urgent surgery (35.6%). FRAIL, CFS and FP predicted mortality and readmissions in several settings, but disability worsening only in cardiology. CONCLUSIONS: Frailty is a highly frequent condition in older people attending non-geriatric hospital departments. We recommend that based upon their current feasibility and predictive ability, the FRAIL scale, CFS and FP should be preferentially used in these settings. The low concordance among the tools and differences in prevalence reported and predictive ability suggest the existence of different subtypes of frailty.

The ability of eight frailty instruments to identify adverse outcomes across different settings: the FRAILTOOLS project.

BACKGROUND: To compare the performance of eight frailty instruments to identify relevant adverse outcomes for older people across different settings over a 12 month follow-up. METHODS: Observational longitudinal prospective study of people aged 75 + years enrolled in different settings (acute geriatric wards, geriatric clinic, primary care clinics, and nursing homes) across five European cities. Frailty was assessed using the following: Frailty Phenotype, SHARE-FI, 5-item Frailty Trait Scale (FTS-5), 3-item FTS (FTS-3), FRAIL scale, 35-item Frailty Index (FI-35), Gérontopôle Frailty Screening Tool, and Clinical Frailty Scale. Adverse outcomes ascertained at follow-up were as follows: falls, hospitalization, increase in limitation in basic (BADL) and instrumental activities of daily living (IADL), and mortality. Sensitivity, specificity, and capacity to predict adverse outcomes in logistic regressions by each instrument above age, gender, and multimorbidity were calculated. RESULTS: A total of 996 individuals were followed (mean age 82.2 SD 5.5 years, 61.3% female). In geriatric wards, the FI-35 (69.1%) and the FTS-5 (67.9%) showed good sensitivity to predict death and good specificity to predict BADL worsening (70.3% and 69.8%, respectively). The FI-35 also showed good sensitivity to predict BADL worsening (74.6%). In nursing homes, the FI-35 and the FTSs predicted mortality and BADL worsening with a sensitivity > 73.9%. In geriatric clinic, the FI-35, the FTS-5, and the FRAIL scale obtained specificities > 85% to predict BADL worsening. No instrument achieved high enough sensitivity nor specificity in primary care. All the instruments predict the risk for all the outcomes in the whole sample after adjusting for age, gender, and multimorbidity. The associations of these instruments that remained significant by setting were for BADL worsening in geriatric wards [FI-35 OR = 5.94 (2.69-13.14), FTS-3 = 3.87 (1.76-8.48)], nursing homes [FI-35 = 4.88 (1.54-15.44), FTS-5 = 3.20 (1.61-6.38), FTS-3 = 2.31 (1.27-4.21), FRAIL scale = 1.91 (1.05-3.48)], and geriatric clinic [FRAIL scale = 4.48 (1.73-11.58), FI-35 = 3.30 (1.55-7.00)]; for IADL worsening in primary care [FTS-5 = 3.99 (1.14-13.89)] and geriatric clinic [FI-35 = 3.42 (1.56-7.49), FRAIL scale = 3.27 (1.21-8.86)]; for hospitalizations in primary care [FI-35 = 3.04 (1.25-7.39)]; and for falls in geriatric clinic [FI-35 = 2.21 (1.01-4.84)]. CONCLUSIONS: No single assessment instrument performs the best for all settings and outcomes. While in inpatients several commonly used frailty instruments showed good sensitivities (mainly for mortality and BADL worsening) but usually poor specificities, the contrary happened in geriatric clinic. None of the instruments showed a good performance in primary care. The FI-35 and the FTS-5 showed the best profile among the instruments assessed.

Higher sRAGE Levels Predict Mortality in Frail Older Adults with Cardiovascular Disease.

INTRODUCTION: The evidence that blood levels of the soluble receptor for advanced glycation end products (sRAGE) predict mortality in people with cardiovascular diseases (CVD) is inconsistent. To clarify this matter, we investigated if frailty status influences this association. METHODS: We analysed data of 1,016 individuals (median age, 75 years) from 3 population-based European cohorts, enrolled in the FRAILOMIC project. Participants were stratified by history of CVD and frailty status. Mortality was recorded during 8 years of follow-up. RESULTS: In adjusted Cox regression models, baseline serum sRAGE was positively associated with an increased risk of mortality in participants with CVD (HR 1.64, 95% CI 1.09-2.49, p = 0.019) but not in non-CVD. Within the CVD group, the risk of death was markedly enhanced in the frail subgroup (CVD-F, HR 1.97, 95% CI 1.18-3.29, p = 0.009), compared to the non-frail subgroup (CVD-NF, HR 1.50, 95% CI 0.71-3.15, p = 0.287). Kaplan-Meier analysis showed that the median survival time of CVD-F with high sRAGE (>1,554 pg/mL) was 2.9 years shorter than that of CVD-F with low sRAGE, whereas no survival difference was seen for CVD-NF. Area under the ROC curve analysis demonstrated that for CVD-F, addition of sRAGE to the prediction model increased its prognostic value. CONCLUSIONS: Frailty status influences the relationship between sRAGE and mortality in older adults with CVD. sRAGE could be used as a prognostic marker of mortality for these individuals, particularly if they are also frail.

A Comparison of Frailty Assessment Instruments in Different Clinical and Social Care Settings: The Frailtools Project.

OBJECTIVE: To determine which of 8 commonly employed frailty assessment tools demonstrate the most appropriate characteristics to be employed in different clinical and social settings. DESIGN: Cross-sectional multicenter European-based study. SETTING AND PARTICIPANTS: 1440 patients aged ≥75 years evaluated in geriatric inpatient wards, geriatric outpatient clinics, primary care clinics, and nursing homes. METHODS: The frailty instruments used were Frailty Phenotype, SHARE-FI, 3-item Frailty Trait Scale (FTS-3), 5-item Frailty Trait Scale (FTS-5), FRAIL, 35-item Frailty Index (FI-35), Gérontopôle Frailty Screening Tool (GFST), and Clinical Frailty Scale (CFS). The settings were geriatrics wards, outpatient clinics, primary care, and nursing homes. Suitability was evaluated by considering the feasibility (patients with the test fully completed), administration time (time spent for administering the test), and interscale agreement (Cohen kappa index among instruments to detect frailty). RESULTS: The prevalence of frailty varied across settings and adopted tests. The scales with the mean highest feasibility were the FRAIL scale (99.4%), SHARE-FI (98.3%), and GFST (95.0%). The mean shortest administration times were obtained with CFS (24 seconds), GFST (72 seconds), and FRAIL scale (90 seconds). The interscale agreement between most of the tests was fair. CFS followed by FTS-5 agreed at least moderately with a greater number of scales overall and in almost all settings. CONCLUSIONS AND IMPLICATIONS: Based on feasibility, time to undertake the tool, and agreement with other scales, different scales would be recommended according to the setting considered. Our findings suggest that most of the tools evaluated are actually assessing different frailty constructs.

Malnutrition Prevalence and Burden on Healthcare Resource Use Among Spanish Community-Living Older Adults: Results of a Longitudinal Analysis.

PURPOSE: Little is known about the economic burden that malnutrition or its risk imposes on community-dwelling older adults. Using cross-sectional and longitudinal analyses, we assessed the impact of malnutrition risk on healthcare utilization and costs in a cohort of older adults living in Spanish community. PATIENTS AND METHODS: Data from 1660 older (range 66-98 years), community-living adults participating in the Toledo Study on Healthy Ageing, waves 2 (year 2011-2013) and 3 (year 2015), were analyzed. Nutritional status categories were defined according to the Global Leadership Initiative on Malnutrition (GLIM) criteria, using a two-step approach. First, screening for malnutrition risk. Once positive, individuals were classified as malnourished according to some phenotypic (body mass index, grip strength, and unintentional weight loss) and etiologic (disease burden/inflammation and reduced food intake or assimilation) criteria. Outcomes assessed included healthcare resources (hospital admissions, number of hospitalizations, length of hospital stay per hospitalization, and number of medications). RESULTS: Fifteen percent of the population was found to be at risk of malnutrition, while 12.6% was malnourished. Overall, patients from both groups were older, had lower functional status, and had more comorbidities compared to well-nourished counterparts (p<0.05). Results of our cross-sectional analysis showed that being at-risk/malnourished was associated with greater medication utilization, higher rates of hospital admission and longer stays, and higher hospitalization costs. However, when adjusting for covariates, malnutrition/risk was associated only with higher hospitalization costs (range: 11-13%). Longitudinal analysis results indicated that malnutrition/risk was significantly associated with more frequent hospitalizations, longer lengths of stay, higher hospitalization costs, and polypharmacy at follow-up. CONCLUSION: Malnutrition or its risk, found in over one of four older adults in the Toledo community, was associated with higher healthcare resource use and increased costs. Such findings suggest that malnutrition risk-screening for older adults, and provision of nutrition counseling and care when needed, hold potential to improve their health and to lower costs of care in the Spanish healthcare system.

Frailty Trait Scale-Short Form: A Frailty Instrument for Clinical Practice.

OBJECTIVES: To develop short versions of the Frailty Trait Scale (FTS) for use in clinical settings. DESIGN: Prospective population-based cohort study. SETTING AND PARTICIPANTS: Data from 1634 participants from the Toledo Study for Healthy Aging. METHODS: The 12-item Frailty Trait Scale (FTS) reduction was performed based on an area under the curve (AUC) analysis adjusted by age, sex, and comorbidity. Items that maximized prognostic information for adverse events were selected. Each item score was done at the same time as the reduction, identifying the score that maximized the predictive ability for adverse events. For each short version of the FTS, cutoffs that optimized the prognostic information (sensitivity and specificity) were chosen, and their predictive value was later compared with a surrogate gold standard for frailty (the Fried Phenotype). RESULTS: Two short forms, the 5-item (FTS5) (range 0-50) and 3-item (FTS3) (range 0-30), were identified, both with AUCs for health adverse events similar to the 12-item FTS. The identified cutoffs were >25 for the FTS5 scale and >15 for the FTS3. The frailty prevalence with these cutoffs was 24% and 20% for the FTS5 and FTS3, respectively, whereas frailty according to Fried Phenotype (FP) reached 8% and prefrailty reached 41%. In general, the FTS5 showed better prognostic performance than the FP, especially with prefrail individuals, in whom the FTS5 form identified 65% of participants with an almost basal risk and 35% with a very high risk for mortality (OR: 4) and frailty (OR: 6.6-8.7), a high risk for hospitalization (OR: 1.9-2.1), and a moderate risk for disability (OR: 1.7) who could be considered frail. The FTS3 form had worse performance than the FTS5, showing 31% of false negatives between frail participants identified by FP with a high risk of adverse events. CONCLUSIONS AND IMPLICATIONS: The FTS5 is a short scale that is easy to administer and has a similar performance to the FTS, and it can be used in clinical settings for frailty diagnosis and evolution.

Drug Induced Liver Injury in Geriatric Patients Detected by a Two-Hospital Prospective Pharmacovigilance Program: A Comprehensive Analysis Using the Roussel Uclaf Causality Assessment Method.

Background/aim: A prospective evaluation of drug-induced liver injury (DILI) in two tertiary hospitals was conducted through a pharmacovigilance program from laboratory signals at hospital (PPLSH) to determine the principal characteristics of DILI in patients older than 65 years, a growing age group worldwide, which is underrepresented in the literature on DILI. Methods: All DILI in patients older than 65 years detected by PPLSH in two hospitals were followed up for 8 years in the La Paz Hospital and 2 years in the Getafe Hospital. A descriptive analysis was conducted that determined the causality of DILI and suspected drugs, the incidence of DILI morbidities, DILI characteristics, laboratory patterns, evolution and outcomes. Results: 458 DILI cases in 441 patients were identified, 31.0% resulting in hospitalisation and 69.0% developing during hospitalisation. The mean age was 76.61 years old (SD, 7.9), and 54.4% were women. The DILI incidence was 76.33/10,000 admissions (95%CI 60.78-95.13). Polypharmacy (taking >4 drugs) was present in 86.84% of patients, 39.68% of whom took >10 drugs. The hepatocellular phenotype was the most frequent type of DILI (53.29%), a higher proportion (65%) had a mild severity index, and, in 55.2% of the evaluated drugs the RUCAM indicated that the causal relationship was highly probable. The most frequently employed drugs were paracetamol (50-cases), amoxicillin-clavulanate (42-cases) and atorvastatin (37-cases). The incidence rate of in-hospital DILI per 10,000 DDDs was highest for piperacillin-tazobactam (66.96/10,000 DDDs). A higher risk of in-hospital DILI was associated with the therapeutic chemical group-J (antiinfectives for systemic use) (OR, 2.65; 95%CI 1.58-4.46) and group-N (central nervous system drugs) (OR, 2.33; 95%CI 1.26-4.31). The patients taking >4 medications presented higher maximum creatinine level (OR, 2.01; 95%CI 1.28-3.15), and the patients taking >10 medications had a higher use of group J drugs (OR, 2.08; 95%IC 1.31-3.32). Conclusion: The incidence rate of DILI in the patients older than 65 years was higher than expected. DILI in elderly patients is mild, has a good outcome, has a hepatocellular pattern, develops during hospitalisation, and prolongs the hospital stay. Knowing the DILI incidence and explanatory factors will help improve the therapy of the elderly population.

Sedentary behaviour, physical activity, and sarcopenia among older adults in the TSHA: isotemporal substitution model.

BACKGROUND: The associations between free-living physical activity (PA) and sedentary behaviour (SB) and sarcopenia in older people and its determinants are controversial. Self-reporting, the use of one-size-fits-all cut-points for intensity categorization when using accelerometers and the absence of a clear sarcopenia definition hampered explorations. The aim of this study is to describe the associations between objectively measured PA patterns and sarcopenia and its determinants. METHODS: Subjects aged >65 with valid accelerometry and sarcopenia-related measures from Toledo Study of Healthy Aging (TSHA) were included. Muscle mass (MM) was estimated by dual-energy X-ray absorptiometry. Handgrip strength (HS) was measured by dynamometry. Physical performance assessment relied on gait speed (GS). Sarcopenia presence was ascertained using Foundation for the National Institutes of Health (FNIH) criteria. PA and SB were estimated by ActiTrainer worn for 1 week and classified into time spent in SB and different PA intensity bands [light PA (LPA) and moderate-to-vigorous PA (MVPA)] using age-specific cut-points. Different multivariate linear and logistic regression models [(i) single-parameter, (ii) partition, and (iii) isotemporal substitution models] were used for estimating associations between PA, SB, and sarcopenia determinants and sarcopenia rates, respectively. All models adjusted for age, sex, co-morbidities (Charlson index), and functional ability (Katz and Lawton indexes). RESULTS: Five hundred twelve subjects from the TSHA had available data (78.08 ± 5.71 years of age; 54.3% women). FNIH sarcopenia assessment was performed in 497 subjects (23.3% were sarcopenic). In the linear regression, the single-parameter model showed an association between MVPA and all sarcopenia determinants. In the partition model, MVPA was associated with greater MM and GS. The isotemporal substitution showed that reallocating 1 h/day of MVPA displacing SB was associated with greater values in MM [ß = 0.014; 95% confidence interval (CI) = 0.004, 0.024; P < 0.01], GS (ß = 0.082; 95% CI = 0.054, 0.110; P < 0.001), and HS (ß = 0.888; 95% CI = 0.145, 1.631; P < 0.05). In the logistic regression, the single-parameter model yielded a significant association between 1 h/day increase in MVPA and sarcopenia reduction [odds ratio (OR) = 0.522; 95% CI = 0.367, 0.726; P < 0.001], as did the partition model (OR = 0.555; 95% CI = 0.376, 0.799; P < 0.01). The reallocation of 1 h/day SB only yielded a significant lower sarcopenia risk by almost 50% when it was substituted with MVPA, whereas the substitution of 15 min/day yielded a significant lower sarcopenia risk by 15% (P < 0.001) but did not show any association when it was substituted with LPA. CONCLUSIONS: An increase in MVPA replacing SB and LPA was associated with a reduction in sarcopenia prevalence and better performance across its determinants (MM, GS, and HS). LPA did not show any significant effect.

FRAILTOOLS study protocol: a comprehensive validation of frailty assessment tools to screen and diagnose frailty in different clinical and social settings and to provide instruments for integrated care in older adults.

BACKGROUND: Dozens of scales and questionnaires have been used in the detection of frailty; however, a generalized method for its screening and diagnosis is still lacking in clinical settings. FRAILTOOLS´ main objective is to evaluate the usefulness of frailty scales in the detection of frailty in different clinical and social settings, and its integration in management algorithms for the frail older patient. METHODS: FRAILTOOLS is an observational, longitudinal and prospective study with a follow-up of 6, 12 and 18 months. People older than 75 years old will be recruited from three separate clinical settings (acute geriatric wards, geriatric outpatient clinics and primary care) and one social setting (nursing homes). Exclusion criteria include Mini-mental State Examination < 20 points, and a Barthel index < 90 points, except in nursing home residents (< 40 points). The participants will be recruited in Spain, Italy, France, United Kingdom and Poland. The total sample size will be of 1.940 subjects, 97 subjects in each clinical setting by center. A personal interview with each participant will take place to register data on comorbidity (Charlson Index), functional (SPPB, Barthel and Lawton indexes), cognitive (MMSE) and frailty status (Fried Phenotype, Frailty Trait Scale - short version, SHARE-FI, 35-Items Rockwood Frailty Index, Clinical Frailty Scale, FRAIL scale and Gérontopôle Frailty Screening Tool) in the baseline visit, month 12 and month 18 visit of follow up. At 6 month a phone call will be made to assess whether there have been falls and to check the vital status. DISCUSSION: Currently, the usefulness of certain assessment tools in social and clinical settings have not been properly assessed, including their ability to predict the individual risk for different adverse outcomes, which is the main interest in daily practice. The FRAILTOOLS project concentrates on providing screening and diagnostic tools for frailty in those settings where its prevalence is the highest and where efforts in prevention could make a significant change in the trend towards disability. TRIAL REGISTRATION: Comprehensive validation of frailty assessment tools in older adults in different clinical and social settings (FRAILTOOLS), NCT02637518 (date of registration: 12/18/2015).

Better Nutritional Status Is Positively Associated with mRNA Expression of SIRT1 in Community-Dwelling Older Adults in the Toledo Study for Healthy Aging.

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.

Cognitive Performance across 3 Frailty Phenotypes: Toledo Study for Healthy Aging.

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.

Frailty Is Associated With Lower Expression of Genes Involved in Cellular Response to Stress: Results From the Toledo Study for Healthy Aging.

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.

The Standardization of Frailty Phenotype Criteria Improves Its Predictive Ability: The Toledo Study for Healthy Aging.

INTRODUCTION: Several studies have assessed the performance of the original frailty phenotype criteria (FPC) and the standardized version according to the characteristics of the population. No studies exist, however, evaluating the impact of this standardization on its predictive ability. OBJECTIVE: To compare how the original FPC and the standardized-frailty phenotype criteria (S-FPC) estimate the prevalence of frailty and their ability to predict mortality, hospitalization, incident disability, and falls. METHODS: Data were taken from the Toledo Study for Healthy Aging, a population-based, community-dwelling study conducted on 1645 individuals over 65. Frailty was operationalized in two ways: FPC, using the cut-off estimated in the Cardiovascular Health Study and S-FPC, using cut-off points fitted to the phenotypic characteristics of our study sample. Frailty prevalences were compared using chi-square statistic. Cox proportional hazard models and logistic regressions evaluated the predictive ability of both tools. Lastly, survival tests were applied. RESULTS: Frailty and prefrailty prevalences varied according to the tool used: 24.12% and 66.40%, respectively when we used FPC and 6.68% and 47.81% when we used S-FPC (P < .01). Regarding their predictive ability, S-FPC, but not FPC, identified consistently the prefrail persons as an intermediate risk group between robust and frail people [death 1.57 (1.15-2.16); hospitalization 1.47 (1.16-1.85); and incident disability 1.96 (1.30-2.97); P < .005]. Furthermore S-FPC predicted death and hospitalization at shorter times than FPC (P < .05). CONCLUSION: FPC should be standardized according to the characteristics of the population in order to improve its predictive ability.

Endocrinology of Aging From a Muscle Function Point of View: Results From the Toledo Study for Healthy Aging.

INTRODUCTION: Aging is a process that involves a reduction in muscle strength and anabolic hormone concentrations, which impacts significantly on health. AIM: To study the hormone/total strength (H/TS) ratio as a proxy of anabolic insensitivity status in elders, and its relationship with disability, hospitalization, and mortality risk. DESIGN: A total of 1462 persons aged ≥65 years from the Toledo Study of Healthy Aging participated in this study. Serum concentrations of insulin like growth factor 1, total and free testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and 17ß-estradiol were measured. Total maximal voluntary isometric strength was obtained (handgrip, shoulder, hip, and knee) using standardized techniques and equipment. Physical activity was recorded by physical activity scale for the elderly questionnaire. Associations of the H/TS ratio with hospitalization and mortality were assessed using logistic regression models, and participants stratified into quartiles for each H/TS ratio. RESULTS: In women, all individual ratio H/TS models showed a strong to moderate increased risk for death and hospitalization. In men, all models revealed a significant positive association of the ratio H/TS with mortality rate but not for hospitalization (P < .01). Participants who have 2 or more H/TS ratios in the worst quartile increased the risk of hospitalization and mortality at least by 2-fold. CONCLUSIONS: We demonstrate the main role that muscle function plays in the relationship between the hormonal status and hospitalization and mortality risk; this could be taken into consideration as a way to classify patients for hormonal therapy.

Serum uric acid concentrations and risk of frailty in older adults.

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 ≥60years 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 1mg/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 1mg/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.

Obesity, fat distribution, and risk of frailty in two population-based cohorts of older adults in Spain.

OBJECTIVE: To evaluate for the first time the longitudinal relationship between abdominal obesity and the onset of frailty. METHODS: Study based on results from two population-based cohorts, the Seniors-ENRICA, with 1801 individuals aged ≥60, and the Toledo Study for Healthy Ageing (TSHA), with 1289 participants ≥65 years. Incident frailty was assessed with the Fried criteria. RESULTS: During 3.5 years of follow-up, 125 individuals with incident frailty in Seniors-ENRICA and 162 in TSHA were identified. After adjustment for the main confounders, the pooled odds ratio (pooled OR) for general obesity and risk of frailty was 1.73 (95% confidence interval [CI]: 1.18-2.28). Abdominal obesity was also associated with frailty (pooled OR: 1.67; 95% CI: 1.09-2.25). Compared with individuals with BMI <25 kg/m(2) and no abdominal obesity, the risk of frailty was highest among individuals with concurrent general and abdominal obesity (pooled OR: 2.55; 95% CI: 1.23-3.86). General obesity was associated with increased risk of exhaustion (pooled OR: 1.66; 95% CI: 1.11-2.21), low physical activity (pooled OR: 1.57; 95% CI: 1.08-2.05), and weakness (pooled OR: 1.63; 95% CI: 1.12-2.05). For abdominal obesity, results were in the same direction, although they showed statistical significance only for weakness (OR: 1.46; 95% CI: 1.11-1.80). CONCLUSIONS: General and abdominal obesity are associated with incident frailty in the elderly.

Efecto del ajuste socioemocional en el rendimiento y las competencias académicas en el contexto escolar: Estudio comparativo / Effect of socio-emotional adjustment on the school achievement and academic competence in school: Cross-informant study

El propósito del trabajo fue estudiar el ajuste socioemocional y los problemas de conducta, en niños de 11 años de edad, y su relación con el rendimiento y las competencias académicas en Educación Primaria. Profesores y madres cumplimentaron la Batería de Socialización (BAS; Silva y Martorell, 1999) en una muestra de 49 niños, pertenecientes a un estudio longitudinal más amplio. El rendimiento académico se evaluó a través de las calificaciones del profesor y de una prueba estandarizada. Las competencias académicas se midieron a través del cuestionario Health Resources Inventory (HRI; Keogh, Juvonen, y Bernheimer, 1989). También se controló el efecto de la inteligencia mediante el CI verbal de los niños. Nuestros resultados indican acuerdo entre profesores y madres en la evaluación del ajuste socioemocional positivo y del retraimiento de los niños, pero señalan discrepancias en la relación que los diferentes aspectos del ajuste socioemocional mantienen con el rendimiento y con las competencias académicas. Estos datos sugieren que las madres tienen una visión cercana a la del profesor en relación con los comportamientos socioemocionales de los niños, pero únicamente la visión del profesor guarda relación con la ejecución académica del niño. Además, tanto la inteligencia como el ajuste socioemocional son necesarios para explicar el rendimiento y las competencias académicas (AU)

The aim of the current study was to examine the role of socio-emotional adjustment and behavioral problems in eleven years old children; as well as their relationships with school achievement and academic competence in Primary School. Teachers and mothers completed the Social Battery (BAS, Silva, & Martorell, 1999) in a sample of 49 children that take part in a longitudinal study. School achievement was measured by standardized test and qualifications in reading and math. The academic competence was evaluated by teachers with a questionnaire (HRI, Keogh, Juvonen, & Bernheimer, 1989). The effect of intelligence was controlled by the IQ. These data showed that intelligence with socio-emotional adjustment were both of them necessary to explain school achievement and academic competences. Also, results showed agreement between mothers and teachers in positive social adjustment and withdrawing. There were discrepancies as to the effect of socio-emotional adjustment on academic competence and school achievement. These data suggest that mothers and teachers agree in their view of children's socio-emotional behavior, but only teachers' views were related to school achievement (AU)