Patterns of Dietary Blood Markers Are Related to Frailty Status in the FRAILOMIC Validation Phase.

The influence of nutritional factors on frailty syndrome is still poorly understood. Thus, we aimed to confirm cross-sectional associations of diet-related blood biomarker patterns with frailty and pre-frailty statuses in 1271 older adults from four European cohorts. Principal component analysis (PCA) was performed based on plasma levels of α-carotene, ß-carotene, lycopene, lutein + zeaxanthin, ß-cryptoxanthin, α-tocopherol, γ-tocopherol and retinol. Cross-sectional associations between biomarker patterns and frailty status, according to Fried's frailty criteria, were assessed by using general linear models and multinomial logistic regression models as appropriate with adjustments for the main potential confounders. Robust subjects had higher concentrations of total carotenoids, ß-carotene and ß-cryptoxanthin than frail and pre-frail subjects and had higher lutein + zeaxanthin concentrations than frail subjects. No associations between 25-Hydroxyvitamin D3 and frailty status were observed. Two distinct biomarker patterns were identified in the PCA results. The principal component 1 (PC1) pattern was characterized by overall higher plasma levels of carotenoids, tocopherols and retinol, and the PC2 pattern was characterized by higher loadings for tocopherols, retinol and lycopene together and lower loadings for other carotenoids. Analyses revealed inverse associations between PC1 and prevalent frailty. Compared to participants in the lowest quartile of PC1, those in the highest quartile were less likely to be frail (odds ratio: 0.45, 95% CI: 0.25-0.80, p = 0.006). In addition, those in the highest quartile of PC2 showed higher odds for prevalent frailty (2.48, 1.28-4.80, p = 0.007) than those in the lowest quartile. Our findings strengthen the results from the first phase of the FRAILOMIC project, indicating carotenoids are suitable components for future biomarker-based frailty indices.

Role of sarcopenia in the frailty transitions in older adults: a population-based cohort study.

BACKGROUND: Frailty and sarcopenia are age-associated syndromes that have been associated with the risk of several adverse events, mainly functional decline and death, that usually coexist. However, the potential role of one of them (sarcopenia) in modulating some of those adverse events associated to the other one (frailty) has not been explored. The aim of this work is to assess the role of sarcopenia within the frailty transitions and mortality in older people. METHODS: Data from the Toledo Study of Healthy Aging (TSHA) were used. TSHA is a cohort of community-dwelling older adults ≥65. Frailty was assessed according with the Frailty Phenotype (FP) and the Frailty Trait Scale-5 (FTS5) at baseline and at follow-up. Basal sarcopenia status was measured with the standardized Foundation for the National Institutes of Health criteria. Fisher's exact test and logistic regression model were used to determine if sarcopenia modified the transition of frailty states (median follow-up of 2.99 years) and Cox proportional hazard model was used for assessing mortality. RESULTS: There were 1538 participants (74.73 ± 5.73; 45.51% men) included. Transitions from robustness to prefrailty and frailty according to FP were more frequent in sarcopenic than in non-sarcopenic participants (32.37% vs. 15.18%, P ≤ 0.001; 5.76% vs. 1.12%; P ≤ 0.001, respectively) and from prefrailty-to-frailty (12.68% vs. 4.27%; P = 0.0026). Improvement from prefrail-to-robust and remaining robust was more frequent in non-sarcopenic participants (52.56% vs. 33.80%, P ≤ 0.001; 80.18% vs 61.15%, P ≤ 0.001, respectively). When classified by FTS5, this was also the case for the transition from non-frail-to-frail (25.91% vs. 4.47%, P ≤ 0.001) and for remaining stable as non-frail (91.25% vs. 70.98%, P ≤ 0.001). Sarcopenia was associated with an increased risk of progression from robustness-to-prefrailty [odds ratio (OR) 2.34 (95% confidence interval, CI) (1.51, 3.63); P ≤ 0.001], from prefrailty-to-frailty [OR(95% CI) 2.50 (1.08, 5.79); P = 0.033] (FP), and from non-frail-to-frail [OR(95% CI) 4.73 (2.94, 7.62); P-value ≤ 0.001]. Sarcopenia does not seem to modify the risk of death associated with a poor frailty status (hazard ratios (HR, 95%) P > 0.05). CONCLUSIONS: Transitions within frailty status, but not the risk of death associated to frailty, are modulated by the presence of sarcopenia.

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

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

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

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

Association of accelerometer-derived step volume and intensity with hospitalizations and mortality in older adults: A prospective cohort study.

PURPOSE: This study aimed to examine the associations of accelerometer-derived steps volume and intensity with hospitalizations and all-cause mortality in older adults. METHODS: This prospective cohort study involved 768 community-dwelling Spanish older adults (78.8 ± 4.9 years, mean ± SD; 53.9% females) from the Toledo Study for Healthy Aging (2012-2017). The number of steps per day and step cadence (steps/min) were derived from a hip-mounted accelerometer worn for at least 4 days at baseline. Participants were followed-up over a mean period of 3.1 years for hospitalization and 5.7 years for all-cause mortality. Cox proportional hazards regression models were used to estimate the individual and joint associations between daily steps and stepping intensity with hospitalizations and all-cause mortality. RESULTS: Included participants walked 5835 ± 3445 steps/day with an intensity of 7.3 ± 4.1 steps/min. After adjusting for age, sex, body mass index (BMI), education, income, marital status and comorbidities, higher step count (hazard ratio (HR) = 0.95, 95% confidence interval (95%CI: 0.90-1.00, and HR = 0.87, 95%CI: 0.81-0.95 per additional 1000 steps) and higher step intensity (HR = 0.95, 95%CI: 0.91-0.99, and HR = 0.89, 95%CI: 0.84-0.95 per each additional step/min) were associated with fewer hospitalizations and all-cause mortality risk, respectively. Compared to the group having low step volume and intensity, individuals in the group having high step volume and intensity had a lower risk of hospitalization (HR = 0.72, 95%CI: 0.52-0.98) and all-cause mortality (HR = 0.60, 95%CI: 0.37-0.98). CONCLUSION: Among older adults, both high step volume and step intensity were significantly associated with lower hospitalization and all-cause mortality risk. Increasing step volume and intensity may benefit older people.

Associations between frailty trajectories and frailty status and adverse outcomes in community-dwelling older adults.

BACKGROUND: The association between frailty and adverse outcomes has been clearly defined. Frailty is associated with age, but different frailty evolution patterns might determine the incidence of adverse outcomes at older ages. So far, few observational studies have examined how distinct frailty trajectories could be associated with differences in the risk of adverse events and assessing whether frailty trajectories could define risk of death, hospitalization, worsening, and incident disability better than one-off assessment. Our hypothesis is that prospective increases in frailty levels are associated with higher risk of adverse events compared with subjects that prospectively decreased frailty levels. METHODS: Participants' data were taken from the Toledo Study of Healthy Ageing. Frailty was evaluated using the Frailty Trait Scale 5 (FTS5), being 0 the lower (the most robust) and 50 the highest (the frailest) score. FTS5 scores at baseline and follow-up (median 5.04 years) were used to construct frailty trajectories according to group-based trajectory modelling (GBTM). Multivariate Cox proportional hazard and logistic regression models were used to explore associations between frailty status and trajectory membership and the adverse outcomes. Deaths were ascertained through the Spanish National Death Index. Disability was evaluated through the Katz Index. Hospitalization was defined as first admission to Toledo Hospital. RESULTS: Nine hundred and seventy-five older adults (mean age 73.14 ± 4.69; 43.38% men) were included. GBTM identified five FTS5 trajectories: worsening from non-frailty (WNF), improving to non-frailty (INF), developing frailty (DF), remaining frail (RF), and increasing frailty (IF). Subjects belonging to trajectories of increasing frailty scores or showing consistently higher frailty levels presented with an increased risk of mortality {DF [hazard ratio (HR), 95% confidence interval (CI)] = 2.01 [1.21-3.32]; RF = 1.92 [1.18-3.12]; IF = 2.67 [1.48-4.81]}, incident [DF (HR, 95% CI) = 2.06 (1.11-3.82); RF = 2.29 (1.30-4.03); IF = 3.55 (1.37-9.24)], and worsening disability [DF (HR, 95% CI) = 2.11 (1.19-3.76); RF = 2.14 (1.26-3.64); IF = 2.21 (1.06-4.62)], compared with subjects prospectively showing decreases in frailty levels or maintaining low FTS5 scores. A secondary result was a significant dose-response relationship between baseline FTS5 score and adverse events. CONCLUSIONS: Belonging to trajectories of prospectively increasing/consistently high frailty scores over time are associated with an increased risk of adverse outcomes compared with maintaining low or reducing frailty scores. Our results support the dynamic nature of frailty and the potential benefit of interventions aimed at reducing its levels on relevant and burdensome adverse outcomes.

Physical activity trajectories, mortality, hospitalization, and disability in the Toledo Study of Healthy Aging.

BACKGROUND: Physical activity (PA) is a recognized contributor to healthy aging. However, the majority of studies exploring its associations with adverse outcomes in cohorts of older adults use single-time PA estimates, which do not consider its dynamic nature. The aim of the present study is to explore the presence of different PA trajectories in the Toledo Study of Healthy Aging and their association with adverse outcomes. Our hypothesis is that prospectively maintaining or increasing PA is associated with a reduced risk of adverse outcomes. METHODS: We used data from 1679 participants enrolled in the Toledo Study of Healthy Aging. Trajectories based on the Physical Activity Scale for the Elderly were identified using group-based trajectory modelling. Cox and logistic regression were used to investigate associations between PA trajectories and mortality and hospitalization, and incident and worsening disability, respectively. Mortality was ascertained by linkage to the Spanish National Death Index; disability was evaluated through the Katz Index; and hospitalization was defined as the first admission to Toledo Hospital. Models were adjusted by age, sex, smoking, Charlson Index, education, cognitive impairment, polypharmacy, and Katz Index at Wave 2. RESULTS: We found four PA-decreasing and one PA-increasing trajectories: high PA-consistent (n = 566), moderate PA-mildly decreasing (n = 392), low PA-increasing (n = 237), moderate PA-consistent (n = 191), and low PA-decreasing (n = 293). Belonging to the high PA-consistent trajectory group was associated with reduced risks of mortality as compared with the low PA-decreasing group [hazard ratio (HR) 1.68; 95% confidence interval (CI) = 1.21-2.31] and hospitalization compared with the low PA-increasing and low PA-decreasing trajectory groups (HR 1.24; 95% CI = 1.004-1.54 and HR 1.25; 95% CI = 1.01-1.55, respectively) and with lower rates of incident [odds ratio (OR) 3.14; 95% CI = 1.59-6.19] and worsening disability (OR 2.16; 95% CI = 1.35-3.45) in relation to the low PA-decreasing trajectory group and at follow-up. Increasing PA during late life (low PA-increasing group) was associated with lower incident disability rates (OR 0.38; 95% CI = 0.19-0.82) compared with decreasing PA (low PA-decreasing group), despite similar baseline PA. CONCLUSIONS: Our results suggest that sustaining higher PA levels during aging might lead to healthy aging, characterized by a reduction in adverse outcomes. Our study supports the need for enhancing PA participation among older populations, with the goal of reducing personal and economic burden in a worldwide aging population.

Duration and Quality of Sleep and Risk of Physical Function Impairment and Disability in Older Adults: Results from the ENRICA and ELSA Cohorts.

Sleep duration and quality have been associated with poor physical function, but both the temporality of the association and the independence of sleep duration and quality are unclear. We examined the prospective association of sleep duration and quality with physical function impairment and disability in older adults. Data were taken from participants in the Seniors-ENRICA (2012-2015, n= 1,773) and in the ELSA cohort (waves 4 and 6, n=4,885) aged ≥60 years. Sleep duration and quality were self-reported. Physical function impairment and disability was obtained either from self-reports (ENRICA and ELSA) or from performance assessment (ENRICA). Logistic regression models were adjusted for potential confounders. After a follow-up of 2.0-2.8 years, no association was found between changes in sleep duration and physical function impairment or disability. However, in both studies, poor general sleep quality was linked to higher risk of impaired agility [OR: 1.93 (95% CI: 1.30-2.86) in Seniors-ENRICA and 1.65 (1.24-2.18) in ELSA study] and mobility [1.46 (0.98-2.17) in Seniors-ENRICA and 1.59 (1.18-2.15) in ELSA study]. Poor general sleep quality was also associated with decreased physical component summary (PCS) [1.39 (1.05-1.83)], disability in instrumental activities of daily living [1.59 (0.97-2.59)] and in basic activities of daily living [1.73 (1.14-2.64)] in Seniors-ENRICA. In addition, compared to those with no sleep complaints, participants with 2 or more sleep complaints had greater risk of impaired agility, impaired mobility, decreased PCS and impaired lower extremity function in both cohorts. Poor sleep quality was associated with higher risk of physical impairment and disability in older adults from Spain and from England.