Carotid-femoral pulse wave velocity score, an estimator of cognitive performance in the elderly: results from the Toledo Study for Healthy Aging.

Ageing-related changes in the vascular wall influence the function of different organs; for this reason, we assessed how arterial stiffness measured by carotid-femoral pulse wave velocity (cf-PWV) modulates: the basal cognitive performance and the change in cognitive performance over the follow-up time. We developed a prospective, population-based cohort study with 1581 participants aged > 65 years were obtained from the Toledo Study for Healthy Aging. Participants from the second wave (2011-2013) were selected for the cross-sectional analysis. Those who also performed the cognitive assessment in the third wave (2015-2017) were selected for the prospective analysis. Arterial stiffness was evaluated by cf-PWV. Multivariate segmented regression models were used to evaluate the association between cf-PWV scores and basal neuropsychological evaluation scores and change of neuropsychological evaluation scores along follow-up. Cross-sectional analysis showed that as cf-PWV grew within the cf-PWV (5- < 10) category an improvement was observed in 7-min test, free short-term memory, and hole peg test. Furthermore, in the cf-PWV (> 13-18) category a decrease was observed in total short-term memory, free long-term memory, and total long-term memory. Prospective analysis showed a progressive worsening of cognitive function as cf-PWV increases within the cf-PWV (> 13-18) category in 7-min test, object denomination, immediate and short-term memory, and hole peg test, while in the cf-PWV (5- < 10) category, there was observed a decrease in Cumulative Executive Dysfunction Index score and short-term memory. In conclusion, a higher cf-PWV score is associated with worse cognitive performance, and with a worse evolution, reinforcing the need to plan interventions to delay arterial stiffness and its consequences.

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.

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.

Cribado poblacional de aneurismas de la aorta abdominal. Estudio piloto en Salamanca / Population screening for abdominal aortic aneurysms. Pilot study in Salamanca

Introducción: una estrategia para reducir la mortalidad de los aneurismas de la aorta abdominal es conocer su existencia en fase asintomática. Así podremos clasificar los pacientes, en función del tamaño del aneurisma, en candidatos a cirugía programada o a seguimiento periódico. Objetivos: conocer la eficacia, la seguridad y la aceptabilidad de un programa piloto de cribado de aneurismas de la aorta abdominal mediante ecografía abdominal realizada en una población de riesgo. Material y métodos: programa organizado por la Real Academia de Medicina y el Instituto de Investigación Biomédica y ejecutado por el Servicio de Angiología, Cirugía Vascular y Endovascular del Hospital Universitario de Salamanca. El cribado se realizó hace un año, en dos carpas situadas en una céntrica plaza de Salamanca. El análisis incluyó a 295 varones ≥ 65 años, residentes en Salamanca capital, de forma libre y gratuita. Se excluyeron aquellos con aneurisma aórtico conocido. Se realizaron: 1) registro de datos; 2) eco Doppler color por especialistas en angiología y cirugía vascular, y 3) encuesta de satisfacción. Todos firmaron un consentimiento informado. Resultados: el diámetro transversal medio de la aorta abdominal fue de 1,81 ± 0,36 cm. Se detectaron 2 aneurismas (diámetro mayor: ≥ 3,0 cm; 3,1 y 4,7 cm) y 3 ectasias aórticas (diámetro ≥ 2,5 y < 3,0 cm). El 98,3 % (290 varones) no presentó ectasia o aneurisma (aorta < 2,5 cm). Tres individuos (obesidad o aire intrabdominal) fueron reevaluados posteriormente. Se analizaron los factores de riesgo y los antecedentes de la población cribada. 180 participantes del cribado (61,0 %) rellenaron anónimamente una encuesta de satisfacción, con resultados muy positivos. Conclusión: si bien el rendimiento de detección fue bajo, la estrategia y el método empleado fueron satisfactorios para el equipo explorador y la población explorada. Este estudio piloto nos permitirá planificar y organizar un segundo cribado más amplio y de nuevos objetivos.(AU)

Introduction: a strategy to reduce the mortality of abdominal aortic aneurysms is to know their existence in theasymptomatic phase. This way we can classify patients, mainly according to the size of the aneurysm, into candi-dates for scheduled elective surgery or periodic follow-up.Objectives: to determine the effectiveness, safety, and acceptability of a pilot screening program for abdominalaortic aneurysms, using abdominal ultrasound, performed in a risk population.Material and methods: program organized by the Royal Academy of Medicine and the Biomedical ResearchInstitute, and carried out by the Angiology and Vascular Surgery service of the University Hospital of Salamanca.The screening was carried out a year ago, in two tents located in a central square in Salamanca. The study included295 men over 65 years of age, residents of Salamanca capital, free of charge. Those with known aortic aneurysmwere excluded. The following were carried out: 1) data recording; 2) color echo-Doppler, by specialists in angiologyand vascular surgery; and 3) satisfaction survey. All signed an informed consent.Results: the mean transverse diameter of the abdominal aorta was 1.81 ± 0.36 cm. Two aneurysms were detect-ed (largest diameter ≥ 3.0 cm; 3.1 and 4.7 cm), and 3 aortic ectasias (diameter ≥ 2.5 and < 3.0 cm). The 98.3 %(290 men) did not present ectasia or aneurysm (aorta < 2.5 cm). Three individuals (obesity or intra-abdominal air) weresubsequently re-evaluated. The risk factors and background of the screened population were analyzed. A satisfactionsurvey was completed freely and anonymously by 180 screening participants (61.0 %) with very positive results.Conclusion: although the detection performance was low, the strategy and method used were satisfactory for theexploring team and the population explored. The present pilot study will allow us to plan and organize a second,broader screening with new objectives.(AU)

How cognitive performance changes according to the ankle-brachial index score in an elderly cohort? Results from the Toledo Study of Healthy Ageing.

In the ageing process, the vascular system undergoes morphological and functional changes that may condition brain functioning; for this reason, the aims of this study were to assess the effect of vascular function indirectly measured by ankle-brachial index (ABI) on both cognitive performance at baseline and change in cognitive performance at end of follow-up. We developed a prospective, population-based, cohort study with 1147 participants aged > 65 years obtained from the Toledo Study for Healthy Ageing who had cognitive assessment and measured ABI in the first wave (2006-2009) were selected for the cross-sectional analysis. Those participants who also performed the cognitive assessment in the second wave (2011-2013) were selected for the prospective analysis. Cognitive impairment diagnosis and symptoms and/or history of cardio/neurovascular disease were used as exclusion criteria. Multivariate segmented regression model was used to assess the associations between ABI and cognitive performance in both the cross-sectional and prospective analyses. As ABI score decreased from 1.4, the cross-sectional analysis showed a higher decrease in cognitive performance and the prospective analysis showed a higher degree of worsening in cognitive performance. Our findings suggest that the ABI, a widespread measure of vascular health in primary care, may be a useful tool for predicting cognitive performance and its evolution.

Pulmonary function is associated with frailty, hospitalization and mortality in older people: 5-year follow-up.

BACKGROUND: The relationship between pulmonary impairment and frailty has rarely been studied in community-dwelling older adults. OBJECTIVE: This study aimed to analyze the association between pulmonary function and frailty (prevalent and incident), identifying the best cut-off points to detect frailty and its association with hospitalization and mortality. METHODS: A longitudinal observational cohort study with 1188 community-dwelling older adults was taken from the Toledo Study for Healthy Aging. The forced expiratory volume in the first second (FEV1) and the forced vital capacity (FVC) were measured with spirometry. Frailty was evaluated using the Frailty Phenotype and Frailty Trait Scale 5. Associations between pulmonary function and frailty, hospitalization and mortality in a 5-year follow-up and the best cut-off points for FEV1 and FVC were analyzed. RESULTS: FEV1 and FVC were associated with frailty prevalence (OR from 0.25 to 0.60), incidence (OR from 0.26 to 0.53), and hospitalization and mortality (HR from 0.35 to 0.85). The cut-off points of pulmonary function identified in this study: FEV1 (≤1.805 L for male and ≤1.165 L for female) and FVC (≤2.385 L for male and ≤1.585 L for female) were associated with incident frailty (OR: 1.71-4.06), hospitalization (HR: 1.03-1.57) and mortality (HR: 2.64-5.17) in individuals with and without respiratory diseases (P < 0.05 for all). CONCLUSION: Pulmonary function was inversely associated with the risk of frailty, hospitalization and mortality in community-dwelling older adults. The cut-off points for FEV1 and FVC to detect frailty were highly associated with hospitalization and mortality in the 5-year follow-up, regardless of the existence of pulmonary diseases.

High levels of soluble RAGE are associated with a greater risk of mortality in COVID-19 patients treated with dexamethasone.

Blood levels of the soluble receptor for advanced glycation end-products (sRAGE) are acutely elevated during the host inflammatory response to infection and predict mortality in COVID-19. However, the prognostic performance of this biomarker in the context of treatments to reduce inflammation is unclear. In this study we investigated the association between sRAGE and mortality in dexamethasone-treated COVID-19 patients. We studied 89 SARS-CoV-2 positive subjects and 22 controls attending the emergency department of a University Teaching Hospital during the second wave of COVID-19 and measured sRAGE at admission. In positive individuals sRAGE increased with disease severity and correlated with the National Early Warning Score 2 (Pearson's r = 0.56, p < 0.001). Fourteen out of 72 patients treated with dexamethasone died during 28 days of follow-up. Survival rates were significantly lower in patients with high sRAGE (> 3532 pg/mL) than in those with low sRAGE (p = 0.01). Higher sRAGE levels were associated with an increased risk of death after adjustment for relevant covariates. In contrast, IL-6 did not predict mortality in these patients. These results demonstrate that sRAGE remains an independent predictor of mortality among COVID-19 patients treated with dexamethasone. Determination of sRAGE could be useful for the clinical management of this patient population.

The medium-term consequences of a COVID-19 lockdown on lifestyle among Spanish older people with hypertension, pulmonary disease, cardiovascular disease, musculoskeletal disease, depression, and cancer.

OBJECTIVES: This study investigated the associations of chronic diseases with changes in lifestyle and health behaviours in older people following the coronavirus disease 2019 (COVID-19) lockdown in Spain and compared the differences in changes over time. METHODS: 1,092 participants (80.3±5.6 years; 66.5% female) from 2 Spanish cohorts were included. Telephone-based questionnaires were conducted to evaluate lifestyle and health risk behaviours at the end of lockdown and 7 months post-lockdown. Participants were classified as having physician-diagnosed chronic diseases based on self-reported data. Cox proportional models adjusted for major confounders were used. RESULTS: Compared to those without the corresponding chronic diseases, older people with hypertension were less likely to report increased alcohol consumption (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55 to 0.99). Pulmonary diseases were associated with lower risks of increased sedentary time (HR, 0.58; 95% CI, 0.39 to 0.86) and worsened sleep quality (HR, 0.56; 95% CI, 0.36 to 0.87), while cardiovascular diseases were associated with a lower risk of decreased sedentary time (HR, 0.58; 95% CI, 0.38 to 0.88). Depression was linked to a higher likelihood of improved diet quality (HR, 1.53; 95% CI, 1.00 to 2.36). Cancer pacients were less likely to have worsened sleep quality (HR, 0.44; 95% CI, 0.22 to 0.89) but more likely to have reduced their frequency of social contact (HR, 2.05; 95% CI, 1.05 to 3.99). CONCLUSIONS: Older people with chronic diseases showed beneficial changes in lifestyle and health risk behaviours after the COVID-19 lockdown. In particular, older people with hypertension, pulmonary disease, and cancer tended to make beneficial lifestyle and health behaviour changes. However, older people with cardiovascular disease and depression engaged in more health risk behaviours.

Dual effects of insulin resistance on mortality and function in non-diabetic older adults: findings from the Toledo Study of Healthy Aging.

Insulin signalling declines with increasing age and impacts skeletal muscle function and longevity in animal models. Our aim was to assess the relationships between insulin resistance (IR) and frailty and mortality in a unique community-dwelling cohort of older people. 991 non-diabetic subjects from the Toledo Study of Healthy Ageing (TSHA) cohort were included. IR was estimated by the homeostasis model assessment index (HOMA-IR) at baseline while frailty was determined by frailty phenotype (FP) and Frailty Trait Scale (FTS) at baseline and after 5-year follow-up. Deaths were also determined. Multivariate regression models were used to analyze the effects of HOMA-IR on outcomes. Age, gender, BMI, education level, cardio- and cerebro-vascular disease, glomerular filtration rate, and disability were included as potential confounding variables in progressive adjustment models. IR determined as increasing log HOMA-IR was inversely associated with risk of mortality. The association remained significant for all adjustment models (HR: 0.64-0.69). When we analyzed survival curves, the higher the HOMA-IR tertile, the lower the mortality rate (highest vs lowest tertile, p = 0.0082). In contrast, IR increased the risk of incident frailty determined by FP (OR 1.81 [1.14-2.87]) as well as deterioration of frailty status determined by worsening in FTS score (OR 1.28 [1.01-1.63]) at 5-year follow-up. In non-diabetic older subjects, IR significantly increases the risk for frailty and functional decline but decreased the risk of death at 5-year follow-up. This finding raises the need of assessing the effect of biomarkers on different outcomes before establishing their role as biomarkers of aging.

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.

Relationship between self-reported visual impairment and worsening frailty transition states in older people: a longitudinal study.

BACKGROUND: Visual impairment (VI) may lead to worsening functional status and disability. Although disability is very difficult to reverse, it is usually preceded by frailty that may be reverted more easily. It is possible that VI is also related to frailty. AIMS: To assess the relationship between VI and worsening of the frailty status. METHODS: Data were taken from the Toledo Study for Healthy Aging (TSHA), a cohort study of community-dwelling people older than 65 years living in one Spanish province who were followed for 5 years. 1181 participants were included. VI was self-reported and frailty was operationalized using the Fried's phenotype adapted to a Spanish population. Models of multivariate logistic regression were built to assess the associations. RESULTS: The mean age was 73.9 (Standard Deviation (SD) = 5 years) and 58.5% were females. Pre-frailty/frailty prevalence at baseline and follow-up were 41.2/5% and 36.2/12.5%, respectively, and VI was reported by 14.1%. After adjusting for age, gender, education level, tobacco consumption, type 2 diabetes mellitus, high blood pressure, cardiovascular disease, depressive symptoms and cognitive status, odds ratios for the development of frailty by VI were 2.5 (95% Confidence Interval (CI) 1.5-4.4) for non-frail, 2.7 (95% CI 1.3-5.7) for pre-frail and 1.9 (CI 0.6-6.00) for robust participants. The frailty domains whose appearance was most increased by VI were slowness, low energy, low physical activity and weakness. DISCUSSION: Our findings support that VI worsens frailty in the early stages of its development (pre-frailty). VI impairs several frailty items at the same time. CONCLUSIONS: Our study highlights the need to assess both VI and frailty for the prevention of frailty and disability in older people.

Association between telomere length, frailty and death in older adults.

Frailty is considered a clinical marker of functional ageing. Telomere length (TL) has been proposed as a biomarker of biological age but its role in human ageing is controversial. The main aim of the study was to evaluate the longitudinal association of TL with incident frailty and mortality in two cohorts of Spanish community-dwelling older adults. TL was determined at baseline in blood samples from older adults included in Toledo Study for Healthy Aging and ENRICA cohorts while frailty was determined by frailty phenotype (FP) at baseline and at follow-up (3.5 years). Deaths occurring during follow-up were also recorded. Associations of TL with frailty and mortality were analysed by logistic regression with progressive adjustment. Data were separately analysed in the two cohorts and in all subjects by performing a meta-analysis. TL was not different between frail and non-frail subjects. Longer telomeres were not associated with lower risk of prevalent frailty. Similarly, TL at baseline failed to predict incident frailty (OR: 1.04 [0.88-1.23]) or even the development of a new FP criterion (OR: 0.97 [0.90-1.05]) at follow-up. Lack of association was also observed when analysing the development of specific FP criteria. Finally, while frailty at baseline was significantly associated with higher risk of death at follow-up (OR: 4.08 [1.97-8.43], p < 0.001), TL did not significantly change the mortality risk (OR: 1.05 [0.94-1.16]). Results show that TL does not predict incident frailty or mortality in older adults. This suggests that TL is not a reliable biomarker of functional age.

Rapid Assessment at Hospital Admission of Mortality Risk From COVID-19: The Role of Functional Status.

OBJECTIVE: To evaluate the role of functional status along with other used clinical factors on the occurrence of death in patients hospitalized with COVID-19. DESIGN: Prospective cohort study. SETTING: Public university hospital (Madrid). PARTICIPANTS AND METHODS: A total of 375 consecutive patients with COVID-19 infection, admitted to a Public University Hospital (Madrid) between March 1 and March 31, 2020, were included in the Prospective Cohort study. Death was the main outcome. The main variable was disability in activities of daily living (ADL) assessed with the Barthel Index. Covariates included sex, age, severity index (Quick Sequential Organ Failure Assessment, qSOFA), polypharmacy (≥5 drugs in the month before admission), and comorbidity (≥3 diseases). Multivariable logistic regression was used to identify risk factors for adverse outcomes. Estimated model coefficients served to calculate the expected probability of death for a selected combination of 5 variables: Barthel Index, sex, age, comorbidities, and severity index (qSOFA). RESULTS: Mean age was 66 years (standard deviation 15.33), and there were 207 (55%) men. Seventy-four patients died (19.8%). Mortality was associated with low Barthel Index (odds ratio per 5-point decrease 1.11, 95% confidence interval 1.03-1.20), male sex (0.23, 0.11-0.47), age (1.07, 1.03-1.10), and comorbidity (2.15, 1.08-4.30) but not with qSOFA (1.29, 0.87-1.93) or polypharmacy (1.54, 0.77-3.08). Calculated mortality risk ranged from 0 to 0.78. CONCLUSIONS AND IMPLICATIONS: Functional status predicts death in hospitalized patients with COVID-19. Combination of 5 variables allows to predict individual probability of death. These findings provide useful information for the decision-making process and management of patients.

Monitoring and Intervention Technologies to Manage Diabetic Older Persons: The CAPACITY Case-A Pilot Study.

Diabetes Mellitus is a chronic disease with a high prevalence among older people, and it is related to an increased risk of functional and cognitive decline, in addition to classic micro and macrovascular disease and a moderate increase in the risk of death. Technology aimed to improve elder care and quality of life needs to focus in the early detection of decline, monitoring the functional evolution of the individuals and providing ways to foster physical activity, to recommend adequate nutritional habits and to control polypharmacy. But apart from all these core features, some other elements or modules covering disease-specific needs should be added to complement care. In the case of diabetes these functionalities could include control mechanisms for blood glucose and cardiovascular risk factors, specific nutritional recommendations, suited physical activity programs, diabetes-specific educational contents, and self-care recommendations. This research work focuses on those core aspects of the technology, leaving out disease-specific modules. These central technological components have been developed within the scope of two research and innovation projects (FACET and POSITIVE, funded by the EIT-Health), that revolve around the provision of integrated, continuous and coordinated care to frail older population, who are at a high risk of functional decline. Obtained results indicate that a geriatric multimodal intervention is effective for preventing functional decline and for reducing the use of healthcare resources if administered to diabetic pre-frail and frail older persons. And if such intervention is supported by the CAPACITY technological ecosystem, it becomes more efficient.

Increased levels of soluble Receptor for Advanced Glycation End-products (RAGE) are associated with a higher risk of mortality in frail older adults.

OBJECTIVE: to evaluate the relationship between serum levels of the soluble Receptor for Advanced Glycation End-products (sRAGE) and mortality in frail and non-frail older adults. METHODS: we studied 691 subjects (141 frail and 550 non-frail) with a median age of 75 years from two population-based cohorts, the Toledo Study of Healthy Aging and the AMI study, who were enrolled to the FRAILOMIC initiative. Multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the relationship between baseline sRAGE and mortality. RESULTS: during 6 years of follow-up 101 participants died (50 frail and 51 non-frail). Frail individuals who died had significantly higher sRAGE levels than those who survived (median [IQR]: 1563 [1015-2248] vs 1184 [870-1657] pg/ml, P = 0.006), whilst no differences were observed in the non-frail group (1262 [1056-1554] vs 1186 [919-1551] pg/ml, P = 0.19). Among frail individuals higher sRAGE levels were associated with an increased risk of death after adjustment for relevant covariates (HR = 2.72 per unit increment in ln-sRAGE, 95%CI 1.48-4.99, P = 0.001). In contrast, in non-frail individuals sRAGE showed no association with mortality. Survival curves demonstrated that among frail individuals the incidence of death was significantly higher in the top sRAGE quartile compared to the three lower quartiles (P = 0.002). Area under the ROC curve analysis demonstrated that for frail individuals, inclusion of sRAGE in the hazard model increased its predictive accuracy by ~3%. CONCLUSIONS: sRAGE is an independent predictor of mortality among frail individuals. Determination of sRAGE in frail subjects could be useful for prognostic assessment and treatment stratification.

Frailty as a Major Factor in the Increased Risk of Death and Disability in Older People With Diabetes.

OBJECTIVES: To assess the role of frailty in predicting death and incident disability in older adults with type 2 diabetes mellitus. DESIGN: Prospective cohort study. SETTING: Community dwelling. PARTICIPANTS: A total of 1825 individuals ≥65 years old recruited between June 2006 and September 2009 were followed for a median of 5.5 years for mortality and 4.98 years for incident functional disability in activities of daily living. Self-reported diabetes, comorbidities (Charlson index), cardio- and cerebrovascular diseases, drug treatments, Frailty Trait Score (FTS) and Frailty Index (FI), activities of daily living, heart rate, and blood pressure among others were collected at baseline. MAIN OUTCOME MEASURES: Survival analysis (Kaplan-Meier), adjusted Cox proportional-hazards models, and binary logistic regression were used to assess the relationship between frailty, comorbidity, and vascular diseases and time to death and incident disability. RESULTS: A total of 363 people had diabetes. Among them, 83 deaths and 84 cases of incident disability occurred during follow-up. People with diabetes died more frequently than those without diabetes [hazard ratio = 1.36, 95% confidence interval (CI) 1.06-1.75; P = .002], showing a poorer functional status at baseline. Survival analysis showed a relationship between frailty quartiles and the risk of death. In the adjusted Cox-models, only age and frailty indices, but not comorbidity or cardio/cerebrovascular diseases, were associated with the risk of death and incident disability after adjusting for measures of frailty. The hazard ratio for death was 1.51 (95% CI 1.28-1.77) and 1.83 (95% CI 1.49-2·26) for each 10 points increase in the FTS and FI; odds ratio for incident disability was 1·64 (95% CI 1.22-2.20) and 1·35 (95% CI 1.09-1.67) when using FI and FTS, respectively. CONCLUSIONS: Frailty is an important risk factor for death and disability in older adults with diabetes, supporting the recent recommendations that frailty status should be routinely assessed in these patients.

Association of regional muscle strength with mortality and hospitalisation in older people.

BACKGROUND: the association between muscular strength, mortality and hospitalisation with ageing can change depending on sex and the body region analysed (e.g. upper and lower limb muscles). OBJECTIVE: to determine the effect of measuring lower and upper extremities muscular strength on the relationship between strength, mortality and hospitalisation risk in elder men and women. DESIGN: a population-based cohort study using data from the Toledo Study for Healthy Aging (TSHA). METHODS: a Spanish population sample of 1,755 elders aged ≥65 years participated in this study. Upper (handgrip and shoulder) and lower limbs (knee and hip) maximal voluntary isometric strength was obtained using standardised techniques and equipment. Cox proportional hazards model was used to examine mortality and hospitalisation over 5.5 and 3 years of follow-up, respectively. RESULTS: after adjustment for potential confounding factors, including co-morbidities and BMI, hazard ratio of death and hospitalisation was significantly lower in the stronger women and men, but showing regional- and sex-specific differences. That is shoulder, knee and hip muscle regions in women and handgrip and shoulder in men (all P < 0.05). There was a cumulative effect of measuring several muscle strengths over the risk of health events (P < 0.05), so that mortality hazard ratio increased by 45% in women and 25% in men per muscular strength (shoulder, grip, knee and hip) in the weaker strength quartile increase (P < 0.01). CONCLUSIONS: regional muscle strength is a predictor of medium-term mortality and hospitalisation in elder men and women. Multiple strength measures including lower and upper body limb muscles are better predictors than a single strength measurement.

Nonlinear relationship between waist to hip ratio, weight and strength in elders: is gender the key?

Visceral fat has a high metabolic activity with deleterious effects on health contributing to the risk for the frailty syndrome. We studied the association between waist to hip ratio (an indirect measure of visceral fat stores) on upper and lower extremities strength. 1741 individuals aged ≥65 participated in this study. The data was obtained from the Toledo Study for Healthy Aging. For each gender, we studied the relationship between the waist-to-hip ratio (WHR), body mass index (BMI) and regional muscle strength (grip, shoulder, knee and hip) using multivariate linear regression and kernel regression statistical models. WHR was higher in men than in women (0.98 ± 0.07 vs. 0.91 ± 0.08, respectively, P < 0.05). In women with high WHR, we observed a decrease in strength especially in those with a normal BMI. As the WHR lowered, the strength increased regardless of the BMI. In men, lower strength was generally related to the lowest and highest WHR's. Maximum strength in men corresponded at a WHR around 1 and the highest BMI. Muscle strength depends on the joined distribution of WHR and BMI according to gender. In consequence, sex, WHR and BMI should be analyzed conjointly to study the relationship among fat distribution, weight and muscle strength.

Oxidative stress is related to frailty, not to age or sex, in a geriatric population: lipid and protein oxidation as biomarkers of frailty.

OBJECTIVES: To ascertain whether indicators of oxidative damage to lipids (malondialdehyde (MDA)) and proteins (protein carbonylation) are biomarkers of frailty, after adjusting for age, sex, and other possible confounders. DESIGN: Cross-sectional cohort study. SETTING: Community. PARTICIPANTS: Toledo Study for Healthy Aging participants (N = 742, aged 65-95), classified as frail (n = 54), prefrail (n = 278) and nonfrail (n = 410) according to the Fried criteria. MEASUREMENTS: Blood plasma was obtained using centrifugation (1,500 G, 15 minutes) and immediately frozen at -80°C. Plasma lipid peroxidation was determined by measuring the MDA formed from lipoperoxides using high-performance liquid chromatography and protein carbonylation was measured using Western blot. RESULTS: Age- and sex-adjusted levels of lipoperoxides (measured as MDA) and protein carbonylation in plasma proved to be related to frailty, even after including possible independent confounders. CONCLUSION: Circulating oxidative damage biomarkers, such as MDA and protein carbonylation, are related to frailty and not to age or sex. These parameters may be considered as potential biomarkers of frailty in the context of a multidisciplinary health-promoting approach for older adults.