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The relationships between blood biomarkers, frailty, and the risk of death of people diagnosed with COVID-19 is unclear. In the current investigation we decided to analyze the collective effect of multiple biomarkers (laboratory markers of inflammation, blood biochemistry deviations, comorbidity, demographics) on mortality in people diagnosed with COVID-19. We analyzed baseline data of one hundred fifty-five patients (age range from twenty-six to ninety-four) diagnosed with COVID-19. Thirty-seven parameters (including major morbidities) were used to derive the frailty index (FI) and calculate the risk of death as a function of FI and individual biomarkers. Discriminative ability was assessed by the area under the receiver-operating characteristic (ROC curves). The mean frailty index was 0.17 (SD = 0.10), FI of those who survived was 0.11 (SD = 0.078) and those who died was 0.22 (SD = 0.093). In a sex-adjusted model, the FI was a more powerful predictor for mortality than age. The ROC analysis showed that models involving FI as a feature have good discriminative ability for predicting COVID-19 mortality: AUC for age was 0.77, for the FI it was 0.82, and for the fully adjusted model (age + FI) it was 0.84. Thus, the systemic effect of multiple biological processes comprising aging are elucidated using the Frailty Index approach. Assessment of the frailty index at the time of admission of a patient with COVID-19 to the clinic can help to predict the high risks of severe disease and mortality. [ABSTRACT FROM AUTHOR]

We have built a computational model for individual aging trajectories of health and survival, which contains physical, functional, and biological variables, and is conditioned on demographic, lifestyle, and medical background information. We combine techniques of modern machine learning with an interpretable interaction network, where health variables are coupled by explicit pair-wise interactions within a stochastic dynamical system. Our dynamic joint interpretable network (DJIN) model is scalable to large longitudinal data sets, is predictive of individual high-dimensional health trajectories and survival from baseline health states, and infers an interpretable network of directed interactions between the health variables. The network identifies plausible physiological connections between health variables as well as clusters of strongly connected health variables. We use English Longitudinal Study of Aging (ELSA) data to train our model and show that it performs better than multiple dedicated linear models for health outcomes and survival. We compare our model with flexible lower-dimensional latent-space models to explore the dimensionality required to accurately model aging health outcomes. Our DJIN model can be used to generate synthetic individuals that age realistically, to impute missing data, and to simulate future aging outcomes given arbitrary initial health states. Author summary: Aging is the process of age-dependent functional decline of biological organisms. This process is high-dimensional, involving changes in all aspects of organism functioning. The progression of aging is often simplified with low-dimensional summary measures to describe the overall health state. While these summary measures of aging can be used predict mortality and are correlated with adverse health outcomes, we demonstrate that the prediction of individual aging health outcomes cannot be done accurately with these low-dimensional measures, and requires a high-dimensional model. This work presents a machine learning approach to model high-dimensional aging health trajectories and mortality. This approach is made interpretable by inferring a network of pairwise interactions between the health variables, describing the interactions used by the model to make predictions and suggesting plausible biological mechanisms. [ABSTRACT FROM AUTHOR]

Background frailty is a public health priority now that the global population is ageing at a rapid rate. A scientifically sound tool to measure frailty and generate population-based reference values is a starting point. Objective in this report, our objectives were to operationalize frailty as deficit accumulation using a standard frailty index (FI), describe levels of frailty in Canadians ≥45 years old and provide national normative data. Design this is a secondary analysis of the Canadian Longitudinal Study on Aging (CLSA) baseline data. Setting/participants about 51,338 individuals (weighted to represent 13,232,651 Canadians), aged 45–85 years, from the tracking and comprehensive cohorts of CLSA. Methods after screening all available variables in the pooled dataset, 52 items were selected to construct an FI. Descriptive statistics for the FI and normative data derived from quantile regressions were developed. Results the average age of the participants was 60.3 years (95% confidence interval [CI]: 60.2–60.5), and 51.5% were female (95% CI: 50.8–52.2). The mean FI score was 0.07 (95% CI: 0.07–0.08) with a standard deviation of 0.06. Frailty was higher among females and with increasing age, and scores >0.2 were present in 4.2% of the sample. National normative data were identified for each year of age for males and females. Conclusions the standardized frailty tool and the population-based normative frailty values can help inform discussions about frailty, setting a new bar in the field. Such information can be used by clinicians, researchers, stakeholders and the general public to understand frailty, especially its relationship with age and sex. [ABSTRACT FROM AUTHOR]

Objectives: To examine the association between blood-brain barrier (BBB) integrity, brain volume and cognitive dysfunction in adult patients with systemic lupus erythematosus (SLE).Methods: A total of 65 ambulatory patients with SLE and 9 healthy controls underwent dynamic contrast-enhanced MRI scanning, for quantitative assessment of BBB permeability. Volumetric data were extracted using the VolBrain pipeline. Global cognitive function was evaluated using a screening battery consisting of tasks falling into five broad cognitive domains, and was compared between patients with normal versus extensive BBB leakage.Results: Patients with SLE had significantly higher levels of BBB leakage compared with controls (p=0.04). Extensive BBB leakage (affecting over >9% of brain volume) was identified only in patients with SLE (16/65; 24.6%), who also had smaller right and left cerebral grey matter volumes compared with controls (p=0.04). Extensive BBB leakage was associated with lower global cognitive scores (p=0.02), and with the presence of impairment on one or more cognitive tasks (p=0.01).Conclusion: Our findings provide evidence for a link between extensive BBB leakage and changes in both brain structure and cognitive function in patients with SLE. Future studies should investigate the mechanisms underlying BBB-mediated cognitive impairment, validate the diagnostic utility of BBB imaging, and determine the potential of targeting the BBB as a therapeutic strategy in patients with SLE. [ABSTRACT FROM AUTHOR]

Frailty indices (FIs) based on continuous valued health data, such as obtained from blood and urine tests, have been shown to be predictive of adverse health outcomes. However, creating FIs from such biomarker data requires a binarization treatment that is difficult to standardize across studies. In this work, we explore a "quantile" methodology for the generic treatment of biomarker data that allows us to construct an FI without preexisting medical knowledge (i.e. risk thresholds) of the included biomarkers. We show that our quantile approach performs as well as, or even slightly better than, established methods for the National Health and Nutrition Examination Survey and the Canadian Study of Health and Aging data sets. Furthermore, we show that our approach is robust to cohort effects within studies as compared to other data-based methods. The success of our binarization approaches provides insight into the robustness of the FI as a health measure, and the upper limits of the FI observed in various data sets, and also highlights general difficulties in obtaining absolute scales for comparing FIs between studies. [ABSTRACT FROM AUTHOR]

Objective: Early frailty may be captured by a frailty index (FI) based entirely on vital signs and laboratory tests. Our aim was to examine associations between a laboratory‐based FI (FI‐Lab) and adverse health outcomes, and investigate how this changed with age. Methods: Up to 8988 individuals aged 20+ years from the 2003‐2004 and 2005‐2006 National Health and Nutrition Examination Survey cohorts were included. Characteristics of the FI‐Lab were compared to those of a self‐reported clinical FI. Associations between each FI and health care use, self‐reported health, and disability were examined in the full sample and across age groups. Results: Laboratory‐based FI scores increased with age but did not demonstrate expected sex differences. Women aged 20‐39 years had higher FI scores than men; this pattern reversed after age 60 years. FI‐Lab scores were associated with poor self‐reported health (odds ratio[95% confidence interval]: 1.46[1.39‐1.54]), high health care use (1.35[1.29‐1.42]), and high disability (1.41[1.32‐1.50]), even among those aged 20‐39 years. Conclusion: Higher FI‐Lab scores were associated with poor health outcomes at all ages. Associations in the youngest group support the notion that deficit accumulation occurs across the lifespan. FI‐Lab scores could be utilized as an early screening tool to identify deficit accumulation at the cellular and molecular level before they become clinically visible. [ABSTRACT FROM AUTHOR]

Examines the use of performance of equilibrium-point hypothesis model for motor control. Presentation of the model based on a logical system with an empirical data; Evaluation on the explanatory and predictive capacity of the model; Relationship between posture and movement.

Background age-specific mortality reduction has been accompanied by a decrease in the prevalence of some diseases and an increase in others. Whether populations are becoming ‘healthier’ depends on which aspect of health is being considered. Frailty has been proposed as an integrative measure to quantify health status. Objective to investigate changes in the near-term lethality of frailty before and after a 20-year interval using the frailty index (FI), a summary of age-related health deficit accumulation. Design baseline data from the Cognitive Function and Ageing Studies (CFAS) in 1991 (n = 7,635) and 2011 (n = 7,762). Setting three geographically distinct UK centres (Newcastle, Cambridgeshire and Nottingham). Subjects individuals aged 65 and over (both institutionalised and community-living). Methods a 30-item frailty score was used, which includes morbidities, risk factors and subjective measures of disability. Missing items were imputed using multiple imputations by chained equations. Binomial regression was used to investigate the relationship between frailty, age, sex and cohort. Two-year mortality was modelled using logistic regression. Results mean frailty was slightly higher in CFAS II (0.19, 95% confidence interval (CI): 0.19–0.20) than CFAS I (0.18, 95% CI: 0.17–0.18). Two-year mortality in CFAS I was higher than in CFAS II (odds ratio (OR) = 1.16, 95% CI: 1.03–1.30). The association between frailty and 2-year mortality was non-linear with an OR of ~1.6 for each 0.10 increment in the FI. Conclusions the relationship between frailty and mortality did not significantly differ across the studies. Severe frailty as an indicator of mortality is shown to be a stable construct. [ABSTRACT FROM AUTHOR]

Objectives: to investigate how frailty and mobility impairment affect recovery of balance and mobility in acutely ill older patients. Design: secondary analysis of cohort study. Setting: general and geriatric medicine inpatient units, QEII Health Sciences Centre, Dalhousie University, Canada. Subjects: four hundred and nine older adults (mean age = 81 ± 7 standard deviation, 64% women). Methods: we constructed a frailty index based on a comprehensive geriatric assessment (FI-CGA), at baseline (2 weeks before admission; mean 0.31 ± 0.10), and on admission (mean 0.40 ± 0.10), and recorded Hierarchical Assessment of Balance and Mobility (HABAM) scores daily. Recovery was measured as the difference in HABAM scores between discharge and admission. Results: the odds of no or incomplete recovery increased by 1.06 (95% confidence interval: 1.01-1.11) for each 0.1 increment in the baseline FI-CGA. Recovery odds were similarly dependent on age, but independent of baseline HABAM scores. Recovery time was related to Day 1 HABAM scores, initial treatment response and change in the FI-CGA from baseline to admission (r = 0.35, P < 0.001). Recovery time was independent of age. Patients whose mobility improved within 48 h (n = 113; 28%) showed greater improvement and quicker recovery. Conclusions: frailer patients are at a greater risk of incomplete or lengthier recovery from impaired mobility and balance. Tracking mobility and balance might help providers, patients and families understand the course of acute illness in older adults. [ABSTRACT FROM AUTHOR]

Aims: frailty is proposed as a summative measure of health status and marker of individual vulnerability. We aimed to investigate the discriminative capacity of a frailty index (FI) derived from interRAI Comprehensive Geriatric Assessment for Acute Care (AC) in relation to multiple adverse inpatient outcomes. Methods: in this prospective cohort study, an FI was derived for 1,418 patients ≥70 years across 11 hospitals in Australia. The interRAI-AC was administered at admission and discharge by trained nurses, who also screened patients daily for geriatric syndromes. Results: in adjusted logistic regression models an increase of 0.1 in FI was significantly associated with increased likelihood of length of stay >28 days (odds ratio [OR]: 1.29 [1.10-1.52]), new discharge to residential aged care (OR: 1.31 [1.10-1.57]), in-hospital falls (OR: 1.29 [1.10-1.50]), delirium (OR: 2.34 [2.08-2.63]), pressure ulcer incidence (OR: 1.51 [1.23-1.87]) and inpatient mortality (OR: 2.01 [1.66-2.42]). For each of these adverse outcomes, the cut-point at which optimal sensitivity and specificity occurred was for an FI > 0.40. Specificity was higher than sensitivity with positive predictive values of 7-52% and negative predictive values of 88-98%. FI-AC was not significantly associated with readmissions to hospital. Conclusions: the interRAI-AC can be used to derive a single score that predicts multiple adverse outcomes in older inpatients. A score of ≤0.40 can well discriminate patients who are unlikely to die or experience a geriatric syndrome. Whether the FI-AC can result in management decisions that improve outcomes requires further study. [ABSTRACT FROM AUTHOR]

When people age their mortality rate increases exponentially, following Gompertz's law. Even so, individuals do not die from old age. Instead, they accumulate age-related illnesses and conditions and so become increasingly vulnerable to death from various external and internal stressors. As a measure of such vulnerability, frailty can be quantified using the frailty index (FI). Larger values of the FI are strongly associated with mortality and other adverse health outcomes. This association, and the insensitivity of the FI to the particular health variables that are included in its construction, makes it a powerful, convenient, and increasingly popular integrative health measure. Still, little is known about why the FI works so well. Our group has recently developed a theoretical network model of health deficits to better understand how changes in health are captured by the FI. In our model, health-related variables are represented by the nodes of a complex network. The network has a scale-free shape or 'topology': a few nodes have many connections with other nodes, whereas most nodes have few connections. These nodes can be in two states, either damaged or undamaged. Transitions between damaged and non-damaged states are governed by the stochastic environment of individual nodes. Changes in the degree of damage of connected nodes change the local environment and make further damage more likely. Our model shows how age-dependent acceleration of the FI and of mortality emerges, even without specifying an age-damage relationship or any other time-dependent parameter. We have also used our model to assess how informative individual deficits are with respect to mortality. We find that the information is larger for nodes that are well connected than for nodes that are not. The model supports the idea that aging occurs as an emergent phenomenon, and not as a result of age-specific programming. Instead, aging reflects how damage propagates through a complex network of interconnected elements. [ABSTRACT FROM AUTHOR]

Background: With aging, health deficits accumulate: people with few deficits for their age are fit, and those with more are frail. Despite recent reports of improved health in old age, how deficit accumulation is changing is not clear. Our objectives were to evaluate changes over 30 years in the degree of deficit accumulation and in the relationship between frailty and mortality in older adults.Methods: We analyzed data from two population based, prospective longitudinal cohorts, assembled in 1971-1972 and 2000-2001, respectively. Residents of Gothenburg Sweden, systematically drawn from the Swedish population registry. The 1901-1902 cohort (N = 973) had a response rate of 84.8%; the 1930 cohort (N = 500) had a response rate of 65.1%. A frailty index using 36 deficits was calculated using data from physical examinations, assessments of physical activity, daily, sensory and social function, and laboratory tests. We evaluated mortality over 12.5 years in relation to the frailty index.Results: Mean frailty levels were the same (x¯ = 0.20, p = .37) in the 1901-1902 cohort as in the 1930 cohort. Although the frailty index was linked to the risk of death in both cohorts, the hazards ratio decreased from 1.67 per 0.1 increment in the frailty index for the first cohort to 1.32 for the second cohort (interaction term p = .005).Discussion: Although frailty was as common at age 70 as before, its lethality appears to be less. Just why this is so should be explored further. [ABSTRACT FROM AUTHOR]

Understanding the heterogeneity in health of older adults is a compelling question in the biology of aging. We analyzed the performance of five measures of health heterogeneity, judging them by their ability to predict mortality. Using clinical and biomarker data on 1,013 participants of the Canadian Study of Health and Aging who were followed for up to 6 years, we calculated two indices of biological age using the Klemera and Doubal method, which controversially includes using chronological age as a "biomarker," and three frailty indices (FIs) that do not include chronological age: a standard clinical FI, an FI from standard laboratory blood tests and blood pressure, and their combination (FI-combined). Predictive validity was tested using Cox proportional hazards analysis and discriminative ability by the area under the receiver-operating characteristic curves. All five measures showed moderate performance that was improved by combining measures to evaluate larger numbers of items. The greatest addition in explanatory power came from the FI-combined that showed the best mortality prediction in an age-adjusted model. More extensive comparisons across different databases are required, but these results do not support including chronological age as a biomarker. [ABSTRACT FROM AUTHOR]

There is general agreement that frailty is a state of heightened vulnerability to stressors arising from impairments in multiple systems leading to declines in homeostatic reserve and resiliency, but unresolved issues persist about its detection, underlying pathophysiology, and relationship with aging, disability, and multimorbidity. A particularly challenging area is the relationship between frailty and hospitalization. Based on the deliberations of a 2014 Canadian expert consultation meeting and a scoping review of the relevant literature between 2005 and 2015, this discussion paper presents a review of the current state of knowledge on frailty in the acute care setting, including its prevalence and ability to both predict the occurrence and outcomes of hospitalization. The examination of the available evidence highlighted a number of specific clinical and research topics requiring additional study. We conclude with a series of consensus recommendations regarding future research priorities in this important area. [ABSTRACT FROM AUTHOR]

People age at different rates. We have proposed that rates of aging can be quantified by the rate at which individuals accumulate health deficits. Earlier estimates, using cross-sectional analyses suggested that deficits accumulated exponentially, at an annual rate of 3.5 %. Here, we estimate the rate of deficit accumulation using longitudinal data from the Canadian National Population Health Survey. By analyzing age-specific trajectories of deficit accumulation in people aged 20 years and over (n = 13,668) followed biannually for 16 years, we found that the longitudinal average annual rate of deficit accumulation was 4.5 % (±0.75 %). This estimate was notably stable during the adult life span. The corresponding average doubling time in the number of deficits was 15.4 (95 % CI 14.82-16.03) years, roughly 30 % less than we had reported from the cross-sectional analysis. Earlier work also established that the average number of deficits accumulated by individuals (N), equals the product of the intensity of environmental stresses (λ) causing damage to the organism, by the average recovery time (W). At the individual level, changes in deficit accumulation can be attributed to both changes in environmental stresses and changes in recovery time. By contrast, at the population level, changes in the number of deficits are proportional to the changes in recovery time. In consequence, we propose here that the average recovery time, W doubles approximately every 15.4 years, independently of age. Such changes quantify the increase of vulnerability to stressors as people age that gives rise to increasing risk of frailty, disability and death. That deficit accumulation will, on average, double twice between ages 50 and 80 highlights the importance of health in middle age on late life outcomes. [ABSTRACT FROM AUTHOR]

Background: In older adults admitted to intensive care units (ICUs), frailty influences prognosis. We examined the relationship between the frailty index (FI) based on deficit accumulation and early and late survival.Methods: Older patients (≥65 years) admitted to a specialized geriatric ICU at the Liuhuaqiao Hospital, Guangzhou, China between July-December 2011 (n = 155; age 82.7±7.1 y; 87.1% men) were followed for 300 days. The FI was calculated as the proportion present of 52 health deficits. FI performance was compared with that of several prognostic scores.Results: The 90-day death rate was 38.7% (n = 60; 27 died within 30 days). The FI score was correlated with the Glasgow Coma Scale, Karnofsky Scale, Palliative Performance Scale, Acute Physiology Score-APACHE II and APACHE IV (r (2) = 0.52 to 0.72, p < 0.001). Patients who died within 30 days had higher mean FI scores (0.41±0.11) than those who survived to 300 days (0.22±0.11; F = 38.91, p < 0.001). Each 1% increase in the FI from the previous level was associated with an 11% increase in the 30-day mortality risk (95% CI: 7%-15%) adjusting for age, sex, and the prognostic scores. The FI discriminated patients who died in 30 days from those who survived with moderately high accuracy (AUC = 0.89±0.03). No one with an FI score >0.46 survived past 90 days.Conclusion: ICU survival was strongly associated with the level of frailty at admission. An FI based on health deficit accumulation may help improve critical care outcome prediction in older adults. [ABSTRACT FROM AUTHOR]

Purpose: we evaluated mortality risk in relation to social vulnerability across levels of frailty among a cohort of older Japanese-American men. Methods: in secondary analysis of the Honolulu-Asia Aging Study (HAAS), participants (n = 3,271) were aged 72-93 years at baseline. A frailty index (FI) created using 58 potential health deficits to quantify participants' frailty level at baseline, with four frailty strata: 0.0 < FI ≤ 0.1 (n = 1,074); 0.1 < FI ≤ 0.20 (n = 1,549); 0.2 < FI ≤ 0.30 (n = 472); FI > 0.3 (n = 176). Similarly, a social vulnerability index was created using 19 self-reported social deficits. Cox proportional hazard modelling was employed to estimate the impact of social vulnerability across the four levels of frailty, accounting for age, smoking, alcohol use and variation in health deficits within each frailty level. Results: for the fittest participants, social vulnerability was associated with mortality (hazards ratio (HR) = 1.04, 95% confidence interval (CI) = 1.01, 1.07; P value = 0.008). Similarly, for those considered at risk for frailty, each social deficit was associated with a 5% increased risk of mortality. For frail individuals, the Cox regression analyses indicated that social vulnerability was not significantly associated with mortality (0.2 < FI ≤ 0.3: HR= 1.016, 95% CI = 0.98, 1.06; P value = 0.442; FI > 0.3: HR = 0.98, 95% CI = 0.93,1.04). Conclusions: for the fittest and at-risk HAAS participants, the accumulation of social deficits was associated with significant increases in mortality risk. For frail individuals (FI > 0.20), the estimation of mortality risk may depend more so on intrinsic factors related to their health. [ABSTRACT FROM AUTHOR]

Background: The relationship between age-related frailty and the underlying processes that drive changes in health is currently unclear. Considered individually, most blood biomarkers show only weak relationships with frailty and ageing. Here, we examined whether a biomarker-based frailty index (FI-B) allowed examination of their collective effect in predicting mortality compared with individual biomarkers, a clinical deficits frailty index (FI-CD), and the Fried frailty phenotype. Methods: We analyzed baseline data and up to 7-year mortality in the Newcastle 85+ Study (n = 845; mean age 85.5). The FI-B combined 40 biomarkers of cellular ageing, inflammation, haematology, and immunosenescence. The Kaplan-Meier estimator was used to stratify participants into FI-B risk strata. Stability of the risk estimates for the FI-B was assessed using iterative, random subsampling of the 40 FI-B items. Predictive validity was tested using Cox proportional hazards analysis and discriminative ability by the area under receiver operating characteristic (ROC) curves. Results: The mean FI-B was 0.35 (SD, 0.08), higher than the mean FI-CD (0.22; SD, 0.12); no participant had an FI-B score <0.12. Higher values of each FI were associated with higher mortality risk. In a sex-adjusted model, each one percent increase in the FI-B increased the hazard ratio by 5.4 % (HR, 1.05; CI, 1.04-1.06). The FI-B was more powerful for mortality prediction than any individual biomarker and was robust to biomarker substitution. The ROC analysis showed moderate discriminative ability for 7-year mortality (AUC for FI-CD = 0.71 and AUC for FI-B = 0.66). No individual biomarker's AUC exceeded 0.61. The AUC for combined FI-CD/FI-B was 0.75. Conclusions: Many biological processes are implicated in ageing. The systemic effects of these processes can be elucidated using the frailty index approach, which showed here that subclinical deficits increased the risk of death. In the future, blood biomarkers may indicate the nature of the underlying causal deficits leading to age-related frailty, thereby helping to expose targets for early preventative interventions. [ABSTRACT FROM AUTHOR]

Introduction: Many factors influence late-life cognitive changes, and evaluating their joint impact is challenging. Typical approaches focus on average decline and a small number of factors. We used multistate transition models and index variables to look at changes in cognition in relation to frailty (accumulation of health deficits), social vulnerability, and protective factors in the Honolulu-Asia Aging Study (HAAS). Methods: The HAAS is a prospective cohort study of 3,845 men of Japanese descent, aged 71 to 93 years at baseline. Cognitive function was measured using the Cognitive Abilities Screening Instrument (CASI). Baseline index variables were constructed of health deficits (frailty), social vulnerabilities, and protective factors. The chances of improvement/ stability/decline in cognitive function and death were simultaneously estimated using multistate transition modeling for 3- and 6-year transitions from baseline. Results: On average, CASI scores declined by 5.3 points (standard deviation (SD) = 10.0) over 3 years and 9.5 points (SD=13.9) over 6 years. After adjusting for education and age, baseline frailty was associated with an increased risk of cognitive decline at 3 years (β = 0.18, 95% confidence interval (CI), 0.08 to 0.29) and 6 years (β = 0.40, 95% CI, 0.27 to 0.54). The social vulnerability index was associated with 3-year changes (β = 0.16, 95% CI, 0.09 to 0.23) and 6-year changes (β = 0.14, 95% CI, 0.05 to 0.24) in CASI scores. The protective index was associated with reductions in cognitive decline over the two intervals (3-year: β = -0.16, 95% CI, -0.24 to -0.09; 6-year: β = -0.21, 95% CI, -0.31 to -0.11,). Conclusions: Research on cognition in late life needs to consider overall health, the accumulation of protective factors, and the dynamics of cognitive change. Index variables and multistate transition models can enhance understanding of the multifactorial nature of late-life changes in cognition. [ABSTRACT FROM AUTHOR]

Objective To characterize clusters of neuropsychiatric symptoms targeted for tracking the disease course in people with dementia, in relation to stage. Methods Baseline symptoms from 2922 subjects from two datasets (one clinic based, one online) were aggregated. Common neuropsychiatric symptoms identified by patients/carers as targets of treatment using a dementia SymptomGuide™ were selected. The Global Deterioration Scale was used for clinic staging, and an artificial neural network algorithm, for staging online subjects. Symptom clusters were detected using multiple correspondence analysis and connectivity graph analysis based on relative risk (RR). In a connectivity graph, each pair of nodes (representing symptoms) is connected if their co-occurrence is statistically significant; direction is indicated as positive if RR > 1 and negative otherwise. Results Neuropsychiatric symptoms were targeted for treatment in 1072 patients (37%). Agitation (37%) and sleep disturbances (28%) were most common symptoms. One cluster (in people with cognitive impairment, no dementia (CIND) or mild dementia) showed significant co-occurrence of anxiety and restlessness; decreased initiative was chiefly seen in isolation. A second cluster (in moderate/severe dementia) was defined by significant co-occurrence of delusions and hallucinations with sleep disturbances; in these subjects, decreased initiative was related to aggression. Conclusions Two analytical methods identified neuropsychiatric symptom clusters targeted to track the disease course. In CIND/mild dementia, a profile of decreased initiative distinct from depression suggests possible executive dysfunction. In moderate/severe dementia, targets more reflected psychotic symptoms. Visual data displays allow the relationships between multiple symptoms to be considered simultaneously, which commonly is how they present in patients. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Treatment for hypertension with antihypertensive medication has been shown to reduce stroke, cardiovascular events, and mortality in older adults, but there is concern that such treatment may not be appropriate in frailer older adults. To investigate whether there is an interaction between effect of treatment for hypertension and frailty in older adults, we calculated the frailty index (FI) for all available participants from the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over, and obtained frailty adjusted estimates of the effect of treatment with antihypertensive medication on risk of stroke, cardiovascular events, and mortality. Methods: Participants in HYVET were randomised 1:1 to active treatment with indapamide sustained release 1.5 mg ± perindopril 2 to 4 mg or to matching placebo. Data relating to blood pressure, comorbidities, cognitive function, depression, and quality of life were collected at entry into the study and at subsequent follow-up visits. The FI was calculated at entry, based on 60 potential deficits. The distribution of FI was similar to that seen in population studies of adults aged 80 years and above (median FI, 0.17; IQR, 0.11-0.24). Cox regression was used to assess the impact of FI at entry to the study on subsequent risk of stroke, total mortality, and cardiovascular events. Models were stratified by region of recruitment and adjusted for sex and age at entry. Extending these models to include a term for a possible interaction between treatment for hypertension and FI provided a formula for the treatment effect as a function of FI. For all three models, the point estimates of the hazard ratios for the treatment effect decreased as FI increased, although to varying degrees and with varying certainty. Results: We found no evidence of an interaction between effect of treatment for hypertension and frailty as measured by the FI. Both the frailer and the fitter older adults with hypertension appeared to gain from treatment. Conclusions: Further work to examine whether antihypertensive treatment modifies frailty as measured by the FI should be explored. [ABSTRACT FROM AUTHOR]

Objectives To analyze the relationship between frailty and survival in older people with intellectual disabilities ( IDs). Design Population-based longitudinal observational study. Setting Three Dutch care provider services. Participants Individuals with borderline to profound ID aged 50 and older (N = 982). Measurements A frailty index ( FI) including 51 health-related deficits was used to measure frailty. Mean follow-up was 3.3 years. The Cox proportional hazards model was used to evaluate the independent effect of frailty on survival. The discriminative ability of the FI was measured using a receiver operating characteristic ( ROC) curve. Results Greater FI values were associated with greater risk of death, independent of sex, age, level of ID, and Down syndrome. There was a nonlinear increase in risk with increasing FI value. For example, mortality risk was 2.17 times as great (95% confidence interval ( CI) = 0.95-4.95) for vulnerable individuals ( FI 0.20-0.29) and 19.5 (95% CI = 9.13-41.8) times as great for moderately frail individuals ( FI 0.40-0.49) as for relatively fit individuals ( FI <0.20). The area under the ROC curve for 3-year survival was 0.78. Conclusion Although the predictive validity of the FI should be further determined, it was strongly associated with 3-year mortality. Care providers working with people with ID should be able to recognize frail clients and act in an early stage to stop or prevent further decline. [ABSTRACT FROM AUTHOR]

Background: A better understanding of the health status of older inpatients could underpin the delivery of more individualised, appropriate health care. Methods: 1418 patients aged ⩾ 70 years admitted to 11 hospitals in Australia were evaluated at admission using the interRAI assessment system for Acute Care. This instrument surveys a large number of domains, including cognition, communication, mood and behaviour, activities of daily living, continence, nutrition, skin condition, falls, and medical diagnosis. Results: Variables across multiple domains were selected as health deficits. Dichotomous data were coded as symptom absent (0 deficit) or present (1 deficit). Ordinal scales were recoded as 0, 0.5 or 1 deficit based on face validity and the distribution of data. Individual deficit scores were summed and divided by the total number considered (56) to yield a Frailty index (FI-AC) with theoretical range 0-1. The index was normally distributed, with a mean score of 0.32 (±0.14), interquartile range 0.22 to 0.41. The 99% limit to deficit accumulation was 0.69, below the theoretical maximum of 1.0. In logistic regression analysis including age, gender and FI-AC as covariates, each 0.1 increase in the FI-AC increased the likelihood of inpatient mortality twofold (OR: 2.05 [95% CI 1.70 - 2.48]). Conclusions: Quantification of frailty status at hospital admission can be incorporated into an existing assessment system, which serves other clinical and administrative purposes. This could optimise clinical utility and minimise costs. The variables used to derive the FI-AC are common to all interRAI instruments, and could be used to precisely measure frailty across the spectrum of health care. [ABSTRACT FROM AUTHOR]

Background: the derivation of a frailty index (FI) based on deficit accumulation from a Comprehensive Geriatric Assessment (CGA) has been criticised as cumbersome. To improve feasibility, we developed a questionnaire based on a CGA that can be completed by care partners (CP-FI-CGA) and assessed its validity.Methods: we enrolled a convenience sample of patients aged 70 or older (n = 203) presenting to emergency medical services (EMS) or geriatric ambulatory care (GAC). To test construct validity, we evaluated the shape of the CP-FI-CGA distribution, including its maximum value, relationship with age and gender. Criterion validity was evaluated by survival analysis and by the correlation between the CP-FI-CGA and specialist-completed FI-CGA.Results: the mean age was 82.2 ± 5.9 years. Most patients were women (62.1%), unmarried (widowed, divorced and single) (59.6%) and lived in their own home or apartment (78.3%). The mean CP-FI-CGA was 0.41 ± 0.15 and was higher in the EMS group (0.45 ± 0.15) than in GAC (0.37 ± 0.14) (P < 0.001). The CP-FI-CGA correlated well with the specialist-completed FI-CGA (0.7; P < 0.05). People who died had a higher CP-FI-CGA than did survivors (0.48 ± 0.13 versus 0.38 ± 0.15). Each 0.01 increase in the FI was associated with a higher risk of death (HR 1.04; 95% CI 1.02–1.06).Conclusion: the CP-FI-CGA has properties that resemble other published FIs and may be useful in busy clinical practice for grading degrees of frailty. It efficiently integrates information from care partners so that it can help guide decision-making. [ABSTRACT FROM AUTHOR]

Background: the derivation of a frailty index (FI) based on deficit accumulation from a Comprehensive Geriatric Assessment (CGA) has been criticised as cumbersome. To improve feasibility, we developed a questionnaire based on a CGA that can be completed by care partners (CP-FI-CGA) and assessed its validity.Methods: we enrolled a convenience sample of patients aged 70 or older (n = 203) presenting to emergency medical services (EMS) or geriatric ambulatory care (GAC). To test construct validity, we evaluated the shape of the CP-FI-CGA distribution, including its maximum value, relationship with age and gender. Criterion validity was evaluated by survival analysis and by the correlation between the CP-FI-CGA and specialist-completed FI-CGA.Results: the mean age was 82.2 ± 5.9 years. Most patients were women (62.1%), unmarried (widowed, divorced and single) (59.6%) and lived in their own home or apartment (78.3%). The mean CP-FI-CGA was 0.41 ± 0.15 and was higher in the EMS group (0.45 ± 0.15) than in GAC (0.37 ± 0.14) (P < 0.001). The CP-FI-CGA correlated well with the specialist-completed FI-CGA (0.7; P < 0.05). People who died had a higher CP-FI-CGA than did survivors (0.48 ± 0.13 versus 0.38 ± 0.15). Each 0.01 increase in the FI was associated with a higher risk of death (HR 1.04; 95% CI 1.02–1.06).Conclusion: the CP-FI-CGA has properties that resemble other published FIs and may be useful in busy clinical practice for grading degrees of frailty. It efficiently integrates information from care partners so that it can help guide decision-making. [ABSTRACT FROM PUBLISHER]

Background. A frailty index (FI) based on the accumulation of deficits typically has a submaximal limit at about 0.70. The objectives of this study were to examine how population characteristics of the FI change in the Honolulu-Asia Aging Study cohort, which has been followed to near-complete mortality. In particular, we were interested to see if the limit was exceeded. Methods. Secondary analysis of six waves of the Honolulu-Asia Aging Study. Men (n = 3,801) aged 71–93 years at baseline (1991) were followed until death (N = 3,455; 90.9%) or July 2012. FIs were calculated across six waves and the distribution at each wave was evaluated. Kaplan–Meier analyses and Cox proportional hazard models were performed to examine the relationship of frailty with mortality. Results. At each wave, frailty was nonlinearly associated with age, with acceleration in later years. The distributions of the FIs were skewed with long right tails. Despite the increasing mortality in each successive wave, the 99% submaximal limit never exceeded 0.65. The risk of death increased with increasing values of the FI (eg, the hazard rate increased by 1.44 [95% CI = 1.39–1.49] with each increment in the baseline FI grouping). Depending on the wave, the median survival of people with FI more than 0.5 ranged 0.84–2.04 years. Conclusions. Even in a study population followed to almost complete mortality, the limit to deficit accumulation did not exceed 0.65, confirming a quantifiable, maximum number of health deficits that older men can tolerate. [ABSTRACT FROM PUBLISHER]

Background: Functional impairment over time is a necessary condition for the diagnosis of dementia. Increasingly, it is recognized that rates of decline may not follow a linear progression. This variability may indicate that dementia in Alzheimer's disease represents disease rather than inevitable aging. In order to investigate decline in function in dementia, we developed a model of the rate of decline in functions in Alzheimer's disease and in other dementias in comparison with normal aging.Methods: Secondary analysis of a cross-sectional, representative sample of Canadians aged 65 and older (N = 2,914) was performed. We calculated a measure identified as an impairment index, defined as the probability of the occurrences of an impairment or disability in a structured clinical examination.Results: The rate of functional decline varies for different diagnostic groups and increases with severity of the disease. The distribution for the rate of decline in dementia is distinct from that in aging without cognitive impairment. In those without cognitive impairment, the distribution is exponential. Elderly persons with dementia of any type showed a log-normal distribution.Conclusions: The difference in the distributions between aging with and without dementia likely reflects fundamental differences in the processes of decline in functions in the two groups. This suggests that the declines seen in persons with dementia are distinct from normal aging. It also has implications for the testing of antidementia medications, in that modeling treatment effects based on an assumption of linear decline is likely to be flawed. [ABSTRACT FROM AUTHOR]

The multidimensional characterization of complex biomedical systems usually demands a large number of cases in order to obtain reliable inferences. Even so, the number of participants in many studies is relatively small as, for example, in typical clinical trials. Here we suggest an approach based on network visualization, combined with resampling, to discern the patterns of relationships among variables. We illustrate how this can be applied to analyze changes in multiple outcomes in people with dementia. The relationships between several dozens of variables were represented by connectivity graphs, drawn by calculating the relative risk of observing a pair of symptoms in an individual to their co-occurrence by chance only. The statistical significance of the relationships was calculated by generating a bootstrap sample. If the null hypothesis (e.g., the relative risks=1 or equivalently, the pointwise mutual information=0) was rejected, the vertices on the graph representing the variables were connected by an edge. The number of edges (the degree of connectivity) reflects the stage of the cognitive impairment, with worse dementia indicated by lower connectivity. Arranging symptoms consistently allows characteristic profiles to be displayed; this in turn can allow patterns of treatment effects to be discerned, with at-a-glance pattern recognition. [ABSTRACT FROM AUTHOR]

Background Older adults are at an increased risk of death, but not all people of the same age have the same risk. Many methods identify frail people (that is, those at increased risk) but these often require time-consuming interactions with health care providers. We evaluated whether standard laboratory tests on their own, or added to a clinical frailty index (FI), could improve identification of older adults at increased risk of death. Methods This is a secondary analysis of a prospective cohort study, where community dwelling and institutionalized participants in the Canadian Study of Health and Aging who also volunteered for blood collection (n = 1,013) were followed for up to six years. A standard FI (FI-CSHA) was constructed from data obtained during the clinical evaluation and a second, novel FI was constructed from laboratory data plus systolic and diastolic blood pressure measurements (FI-LAB). A combined FI included all items from each index. Predictive validity was tested using Cox proportional hazards analysis and discriminative ability by the area under receiver operating characteristic (ROC) curves. Results Of 1,013 participants, 51.3% had died by six years. The mean baseline value of the FI-LAB was 0.27 (standard deviation 0.11; range 0.05 to 0.63), the FI-CSHA was 0.25 (0.11; 0.02 to 0.72), and the combined FI was 0.26 (0.09; 0.06 to 0.59). In an age- and sex-adjusted model, with each increment in the FI-LAB, the hazard ratios increased by 2.8% (95% confidence interval 1.02 to 1.04). The hazard ratios for the FI-CSHA and the combined FI were 1.02 (1.01 to 1.03) and 1.04 (1.03 to 1.05), respectively. The FI-LAB and FI-CSHA remained independently associated with death in the face of the other. The areas under the ROC curves were 0.72 for FI-LAB, 0.73 for FI-CSHA and 0.74 for the combined FI. Conclusions An FI based on routine laboratory data can identify older adults at increased risk of death. Additional evaluation of this approach in clinical settings is warranted. [ABSTRACT FROM AUTHOR]

Introduction Many age-related health problems have been associated with dementia, leading to the hypothesis that late-life dementia may be determined less by specific risk factors, and more by the operation of multiple health deficits in the aggregate. Our study addressed (1) how the predictive value of dementia risk varies by the number of deficits considered and (2) how traditional (e.g. vascular risks) and nontraditional risk factors (e.g., foot problems, nasal congestion) compare in their predictive effects. Methods Older adults in the Canadian Study of Health and Aging who were cognitively healthy at baseline were analyzed (men = 2,902, women = 4,337). Over ten years, 44.8% men and 33.4% women died; 7.4% men and 9.1% women without baseline cognitive impairment developed dementia. Self-rated health problems, including, but not restricted to, dementia risk factors, were coded as deficit present/absent. Different numbers of randomly selected variables were used to calculate various iterations of the index, i.e. the proportion of deficits present in an individual. Risks for ten-year mortality and dementia outcomes were evaluated separately for men and women using Logistic regression, adjusted for age. The prediction accuracy was evaluated using C-statistics. Results Age-adjusted Odds Ratios per additional deficit were 1.22 (95% confidence interval (CI) 1.18 to 1.26) in men and 1.14 (1.11 to 1.16) in women in relation to death, and 1.18 (1.12 to 1.25) in men and 1.08 (1.04 to 1.11) in women in relation to dementia. The predictive value increased with the number (n) of deficits considered, regardless whether they were known dementia risks, and stabilized at n > 25. The all-factor index best predicted dementia (Cstatistics: 0.67 ± 0.03). Conclusions The variety of items associated with dementias suggests that some part of the risk might relate more to aberrant repair process, than to specifically toxic results. The epidemiology of late life illness might best consider overall health status. [ABSTRACT FROM AUTHOR]

In this article, we present the novel approach of using a multi-state model to describe longitudinal changes in cognitive test scores. Scores are modelled according to a truncated Poisson distribution, conditional on survival to a fixed endpoint, with the Poisson mean dependent upon the baseline score and covariates. The model provides a unified treatment of the distribution of cognitive scores, taking into account baseline scores and survival. It offers a simple framework for the simultaneous estimation of the effect of covariates modulating these distributions, over different baseline scores. A distinguishing feature is that this approach permits estimation of the probabilities of transitions in different directions: improvements, declines and death. The basic model is characterised by four parameters, two of which represent cognitive transitions in survivors, both for individuals with no cognitive errors at baseline and for those with non-zero errors, within the range of test scores. The two other parameters represent corresponding likelihoods of death. The model is applied to an analysis of data from the Canadian Study of Health and Aging (1991–2001) to identify the risk of death, and of changes in cognitive function as assessed by errors in the Modified Mini-Mental State Examination. The model performance is compared with more conventional approaches, such as multivariate linear and polytomous regressions. This model can also be readily applied to a wide variety of other cognitive test scores and phenomena which change with age. [ABSTRACT FROM PUBLISHER]

Background. On average, as people age, they accumulate more health deficits and have an increased risk of death. The deficit accumulation–based frailty index (FI) can quantify health and its outcomes in aging. Previous studies have suggested that women show higher FI values than men and that the highest FI score (the “limit to frailty”) occurs at a value of FI ~ 0.7. Even so, gender differences in the limit to frailty have not been reported. Methods. Data for this analysis were obtained from the Beijing Longitudinal Study of Aging that involved 3,257 community-dwelling Chinese people, aged 55+ years at baseline. The main outcome measure was 5-year mortality. An FI consisting of 35 health-related variables was constructed. The absolute and 99% FI limits were calculated for different age groups and analyzed by sex. Results. The mean level of the FI increased with age and was lower in men than in women (F = 67.87, p < .001). The 99% FI limit leveled off slightly earlier with a relatively lower value in men (60 years; 0.44 ± 0.02) compared with that in women (65 years; 0.52 ± 0.04). The highest absolute FI value was 0.61 in men and 0.69 in women. In both groups, people with an FI greater than or equal to the 99% limit showed close to 100% mortality by 5 years. Conclusion. Compared with men, women appeared to better tolerate deficits in health, yielding both relatively lower mortality and higher limit values to the FI. Even so, the FI did not exceed 0.7 in any individual. [ABSTRACT FROM PUBLISHER]

Objectives To determine whether commonly used frailty scales exhibit shared characteristics when applied to a representative sample of middle-aged and older Europeans. Design Secondary analysis of the Survey of Health, Ageing, and Retirement in Europe ( SHARE). Setting Eleven European countries. Participants Community-dwelling adults (N = 27,527; mean age 65.3 ± 10.5, 55% female). Measurements Frailty was assessed using SHARE-operationalized versions of seven frailty scales: Edmonton Frail Scale, FRAIL scale, Groningen Frailty Indicator, frailty phenotype, Tilburg Frailty Indicator, a 70-item frailty index ( FI), and a 44-item frailty index based on Comprehensive Geriatric Assessment. Results All frailty scales demonstrated right-skewed density distributions. On all scales, frailty scores increased nonlinearly with age, between 1% ( FRAIL) and 3.6% ( FI) per year on a log scale. Frailty scores on all scales exhibited dose-response relationships with 5-year mortality. On all scales, women had higher frailty scores than men of the same age but demonstrated better survival than did men with the same frailty score. On all scales except the frailty phenotype, 99% of participants had scores below the scale's theoretical maximum. Conclusion On each frailty scale, frailty score increased nonlinearly with age, mortality risk increased with frailty score, and women had higher scores than men but demonstrated better survival. Each scale except the frailty phenotype demonstrated an upper limit to frailty below the scale's theoretical maximum. Across commonly used frailty scales, these characteristics are common in nature but differ in magnitude. [ABSTRACT FROM AUTHOR]

Objectives To evaluate transitions in health status and risk of death in older adults in relation to baseline health deficits and protective factors. Design Prospective cohort study with reassessments at 5, 8, and 15 years. Setting Secondary analysis of data from the Beijing Longitudinal Study on Aging. Participants Urban and rural community-dwelling people aged 55 and older at baseline (n = 3,275), followed from 1992 to 2007, during which time 51% died. Measurements Health status was quantified using the deficit accumulation-based frailty index (FI), constructed from 30 intrinsic health measures. A protection index was constructed using 14 extrinsic items (e.g., exercise, education). The probabilities of health changes, including death, were evaluated using a multistate transition model. Results Women had more health deficits (mean baseline FI 0.13 ± 0.11) than did men (mean baseline FI 0.11 ± 0.10). Although health declined on average (mean FIs increased), improvement and stability were common. Baseline health significantly affected health transitions and survival over various follow-up durations (odds ratio (OR) = 1.27, 95% confidence interval (CI) = 1.17-1.37 for men; OR = 1.24, 95% CI = 1.16-1.33 for women for each increment of deficits). Each protective factor reduced the risk of health decline and the risk of death in men and women by 13% to 25%. Conclusion Deficit accumulation-based transition modeling demonstrates persisting effects of baseline health status on age-related health outcomes. Some mitigation by protective factors can be demonstrated, suggesting that improving physical and social conditions might be beneficial. [ABSTRACT FROM AUTHOR]

Background The frailty index (FI) is used to measure the health status of ageing individuals. An FI is constructed as the proportion of deficits present in an individual out of the total number of age-related health variables considered. The purpose of this study was to systematically assess whether dichotomizing deficits included in an FI affects the information value of the whole index. Methods Secondary analysis of three population-based longitudinal studies of community dwelling individuals: Nova Scotia Health Survey (NSHS, n = 3227 aged 18+), Survey of Health, Ageing and Retirement in Europe (SHARE, n = 37546 aged 50+), and Yale Precipitating Events Project (Yale-PEP, n = 754 aged 70+). For each dataset, we constructed two FIs from baseline data using the deficit accumulation approach. In each dataset, both FIs included the same variables (23 in NSHS, 70 in SHARE, 33 in Yale-PEP). One FI was constructed with only dichotomous values (marking presence or absence of a deficit); in the other FI, as many variables as possible were coded as ordinal (graded severity of a deficit). Participants in each study were followed for different durations (NSHS: 10 years, SHARE: 5 years, Yale PEP: 12 years). Results Within each dataset, the difference in mean scores between the ordinal and dichotomous-only FIs ranged from 0 to 1.5 deficits. Their ability to predict mortality was identical; their absolute difference in area under the ROC curve ranged from 0.00 to 0.02, and their absolute difference between Cox Hazard Ratios ranged from 0.001 to 0.009. Conclusions Analyses from three diverse datasets suggest that variables included in an FI can be coded either as dichotomous or ordinal, with negligible impact on the performance of the index in predicting mortality. [ABSTRACT FROM AUTHOR]

Background In Canada, the rise of private-pay assisted living facilities is changing the long-term care landscape. Even so, few clinical implications of having these facilities in the spectrum of care have been studied. Our objective was to compare events and symptoms that might predispose and precipitate a move of older adults to assisted living or to a nursing home. Methods Cross-sectional, descriptive Nova Scotia survey of residents and family members on admission. Health-care use and dementia diagnosis were recorded from the admission record. Dementia was staged using the Global Deterioration Scale and the Dependence Scale. The SymptomGuide, a standardized dementia symptom inventory, was used to assay which symptoms were most influential in the decision to seek long term care. Caregiver stress was elicited by a self-report questionnaire. Results Of 353 people admitted during the enrolment period, 174 (49%) took part in the survey. Most (97; 55.7%) were involved in a move from the community to a nursing home, 54 (31.0%) from the community to assisted living, and 23 (13.2%) from assisted living to a nursing home. In each setting, dementia was the commonest predisposing factor (seen in >90%) with a precipitating event seen in 120 (69%) people. The precipitating events included a medical illness (n = 97; 55%) or caregiver illness, death or move (33; 19%). Dependence was associated with place of care, with more severely impaired people more commonly represented in people who moved to nursing homes. Conclusions People move from the community chiefly due to dementia, and often with a precipitant. Compared with a move to assisted living, moving to nursing homes generally indicates greater dependence, and typically worse dementia severity. Even so, assisted-living facilities are not just for the "worried well", but are used by people with dementia, caregiver stress, and recent hospitalization. [ABSTRACT FROM AUTHOR]

Background: prognostication for frail older adults is complex, especially when they become seriously ill.Objectives: to test the measurement properties, especially the predictive validity, of a frailty index based on a comprehensive geriatric assessment (FI-CGA) in an acute care setting in relation to the risk of death, length of stay and discharge destination.Design and setting: prospective cohort study. Inpatient medical units in a teaching, acute care hospital.Subjects: individuals on inpatient medical units in a hospital, n = 752, aged 75+ years, were evaluated on their first hospital day; to test reliability, a subsample (n = 231) was seen again on Day 3.Measurements: all frailty data collected routinely as part of a CGA were used to create the FI-CGA. Mortality data were reviewed from hospital records, claims data, Social Security Death Index and interviews with Discharge Managers.Results: thirty-day mortality was 93 (12.4%; 95% confidence interval (CI) = 10–15%) of whom 52 died in hospital. The risk of dying increased with each 0.01 increment in the FI-CGA: hazard ratio (HR) = 1.05, (95% CI = 1.04–1.07). People who were discharged home had the lowest admitting mean FI-CGA = 0.38 (±standard deviation 0.11) compared with those who died, FI-CGA = 0.51 (±0.12) or were discharged to nursing home, FI-CGA = 0.49 (±0.11). Likewise, increasing FI-CGA values on admission were significantly associated with a longer length of hospital stay.Conclusions: frailty, measured by the FI-CGA, was independently associated with a higher risk of death and other adverse outcomes in older people admitted to an acute care hospital. [ABSTRACT FROM AUTHOR]

Background: prognostication for frail older adults is complex, especially when they become seriously ill.Objectives: to test the measurement properties, especially the predictive validity, of a frailty index based on a comprehensive geriatric assessment (FI-CGA) in an acute care setting in relation to the risk of death, length of stay and discharge destination.Design and setting: prospective cohort study. Inpatient medical units in a teaching, acute care hospital.Subjects: individuals on inpatient medical units in a hospital, n = 752, aged 75+ years, were evaluated on their first hospital day; to test reliability, a subsample (n = 231) was seen again on Day 3.Measurements: all frailty data collected routinely as part of a CGA were used to create the FI-CGA. Mortality data were reviewed from hospital records, claims data, Social Security Death Index and interviews with Discharge Managers.Results: thirty-day mortality was 93 (12.4%; 95% confidence interval (CI) = 10–15%) of whom 52 died in hospital. The risk of dying increased with each 0.01 increment in the FI-CGA: hazard ratio (HR) = 1.05, (95% CI = 1.04–1.07). People who were discharged home had the lowest admitting mean FI-CGA = 0.38 (±standard deviation 0.11) compared with those who died, FI-CGA = 0.51 (±0.12) or were discharged to nursing home, FI-CGA = 0.49 (±0.11). Likewise, increasing FI-CGA values on admission were significantly associated with a longer length of hospital stay.Conclusions: frailty, measured by the FI-CGA, was independently associated with a higher risk of death and other adverse outcomes in older people admitted to an acute care hospital. [ABSTRACT FROM PUBLISHER]

The health of individuals is highly heterogeneous, as is the rate at which they age. To account for such heterogeneity, we have suggested that an individual’s health status can be represented by the number of health deficits (broadly defined by biological and clinical characteristics) that they accumulate. This allows health to be expressed in a single number: the frailty index (FI) is the ratio of the deficits present in a person to the total number of deficits considered (e.g. in a given database or experimental procedure). Changes in the FI characterize the rate of individual aging. The behavior of the FI is highly characteristic: it shows an age specific, nonlinear increase, (similar to Gompertz law), higher values in females, strong associations with adverse outcomes (e.g., mortality), and a universal limit to its increase (at FI ~0.7). These features have been demonstrated in dozens of studies. Even so, little is known about the origin of deficit accumulation. Here, we apply a stochastic dynamics framework to illustrate that the average number of deficits present in an individual is the product of the average intensity of the environmental stresses and the average recovery time. The age-associated increase in recovery time results in the accumulation of deficits. This not only explains why the number of deficits can be used to estimate individual differences in aging rates, but also suggests that targeting the recovery rate (e.g. by preventive or therapeutic interventions) will decrease the number of deficits that individuals accumulate and thereby benefit life expectancy. [ABSTRACT FROM AUTHOR]

Objectives To operationalize frailty using eight scales and to compare their content validity, feasibility, prevalence estimates of frailty, and ability to predict all-cause mortality. Design Secondary analysis of the Survey of Health, Ageing and Retirement in Europe ( SHARE). Setting Eleven European countries. Participants Individuals aged 50 to 104 (mean age 65.3 ± 10.5, 54.8% female, N = 27,527). Measurements Frailty was operationalized using SHARE data based on the Groningen Frailty Indicator, the Tilburg Frailty Indicator, a 70-item Frailty Index ( FI), a 44-item FI based on a Comprehensive Geriatric Assessment ( FI- CGA), the Clinical Frailty Scale, frailty phenotype (weighted and unweighted versions), the Edmonton Frail Scale, and the FRAIL scale. Results All scales had fewer than 6% of cases with at least one missing item, except the SHARE-frailty phenotype (11.1%) and the SHARE-Tilburg (12.2%). In the SHARE-Groningen, SHARE-Tilburg, SHARE-frailty phenotype, and SHARE- FRAIL scales, death rates were 3 to 5 times as high in excluded cases as in included ones. Frailty prevalence estimates ranged from 6% ( SHARE- FRAIL) to 44% ( SHARE-Groningen). All scales categorized 2.4% of participants as frail. Of unweighted scales, the SHARE- FI and SHARE-Edmonton scales most accurately predicted mortality at 2 ( SHARE- FI area under the receiver operating characteristic curve ( AUC) = 0.77, 95% confidence interval ( CI) = 0.75-0.79); SHARE-Edmonton AUC = 0.76, 95% CI = 0.74-0.79) and 5 (both AUC = 0.75, 95% CI = 0.74-0.77) years. The continuous score of the weighted SHARE-frailty phenotype ( AUC = 0.77, 95% CI = 0.75-0.78) predicted 5-year mortality better than the unweighted SHARE-frailty phenotype ( AUC = 0.70, 95% CI = 0.68-0.71), but the categorical score of the weighted SHARE-frailty phenotype did not ( AUC = 0.70, 95% CI = 0.68-0.72). Conclusion Substantive differences exist between scales in their content validity, feasibility, and ability to predict all-cause mortality. These frailty scales capture related but distinct groups. Weighting items in frailty scales can improve their predictive ability, but the trade-off between specificity, predictive power, and generalizability requires additional evaluation. [ABSTRACT FROM AUTHOR]

Background: on an individual level, lower-income has been associated with disability, morbidity and death. On a population level, the relationship of economic indicators with health is unclear.Objective: the purpose of this study was to evaluate relative fitness and frailty in relation to national income and healthcare spending, and their relationship with mortality.Design and setting: secondary analysis of data from the Survey of Health, Ageing and Retirement in Europe (SHARE); a longitudinal population-based survey which began in 2004.Subjects: a total of 36,306 community-dwelling people aged 50 and older (16,467 men; 19,839 women) from the 15 countries which participated in the SHARE comprised the study sample. A frailty index was constructed as the proportion of deficits present in relation to the 70 deficits available in SHARE. The characteristics of the frailty index examined were mean, prevalence of frailty and proportion of the fittest group.Results: the mean value of the frailty index was lower in higher-income countries (0.16 ± 0.12) than in lower-income countries (0.20 ± 0.14); the overall mean frailty index was negatively correlated with both gross domestic product (r = −0.79; P < 0.01) and health expenditure (r = −0.63; P < 0.05). Survival in non-frail participants at 24 months was not associated with national income (P = 0.19), whereas survival in frail people was greater in higher-income countries (P < 0.05).Conclusions: a country's level of frailty and fitness in adults aged 50+ years is strongly correlated with national economic indicators. In higher-income countries, not only is the prevalence of frailty lower, but frail people also live longer. [ABSTRACT FROM AUTHOR]

Background: all cardiometabolic disorders become more common with age. Frailty and increased vulnerability to adverse outcomes are also common with aging. Even so, how commonly elderly people who are affected by cardiometabolic disorders are also frail remains unclear.Objectives: (i) to evaluate the prevalence of cardiometabolic disorders in relation to frailty. (ii) To estimate to which extent cardiometabolic diseases, when compared with frailty, affects mortality.Methods: this is a secondary analysis of the Beijing Longitudinal Study of Ageing, a population-based representative cohort study (n = 3,257) assembled in 1992 and followed to 2007. The baseline frailty index (FI) considered 35 potential health deficits. People with an FI >0.22 were considered frail. The relationships between frailty and cardiometabolic disorders and mortality outcomes were evaluated using the Cox proportional hazard model, adjusted for baseline age, sex and education.Results: the mean FI was 0.11 in men (SD = 0.10) and 0.14 (SD = 0.11) in women. On average, the FI increased with each cardiometabolic disorder (e.g. in men, mean ± SD = 0.16 ± 0.11 with hypertension, 0.23 ± 0.14 with stroke). As the number of disorders increased, so did the mean FI, and the proportion with the FI >0.22. For each condition, people with the FI >0.22 had a higher mortality, even after adjusting for sex, age and education.Conclusion: cardiometabolic disorders do not occur in isolation and commonly increase not just together, but in the presence of other health deficits. Healthcare providers who work with older adults with such problems need to develop methods to adapt their treatments to the needs of frail older adults. [ABSTRACT FROM PUBLISHER]

Background: it has been observed that a frailty index (FI) is limited by the value of 0.7. Whether this holds in countries with higher mortality rates is not known.Objectives: to test for and quantify a limit in very old Chinese adults and to relate mortality risk to the FI.Design: secondary analysis of four waves (1998, 2000, 2002 and 2005) of the Chinese Longitudinal Health and Longevity Study (CLHLS).Subjects: a total of 6,300 people from 22 of 31 provinces in China, aged 80–99 years at baseline and followed up to 7 years.Methods: an FI was calculated as the ratio of actual to 38 possible health deficits. Frequency distributions were used to evaluate the limit to the FI. Logistic regression and survival analysis were used to evaluate the relationship between the FI and mortality.Results: at each wave, a 99% submaximal limit to frailty was observed at FI = 0.7, despite consecutive losses to death. The death rate for those who were healthiest at baseline (i.e. those in whom the baseline FI = 0) increased from 0.18 at the 2-year follow-up to 0.69 by 7 years. At each wave, 100% mortality at 2 years was observed at FI close to 0.67. A baseline FI >0.45 was associated with 100% 7-year mortality.Conclusions: a limit to frailty occurred with FI = 0.7 which was not exceeded at any age or in any wave. There appears to be a demonstrable limit to the number of health problems that people can tolerate. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Smoking is common in China, where the population is aging rapidly. This study evaluated the relationship between smoking and frailty and their joint association with health and survival in older Chinese men and women. METHODS: Data came from the Beijing Longitudinal Study of Aging, a representative cohort study with a 15-year follow-up. Community-dwelling people (n = 3257) aged more than 55 years at baseline were followed between 1992 and 2007, during which time 51% died. A frailty index (FI) was constructed from 28 self-reported health deficits. RESULTS: Almost half (1,485 people; 45.6%) of the participants reported smoking at baseline (66.8% men, 25.3% women). On average, male smokers were frailer (FI = 0.17±0.13) than male nonsmokers (FI = 0.13±0.10; p = .038). No such differences were seen in women. Men who smoked had the lowest survival probability; female nonsmokers had the highest. Compared with female nonsmokers, the risk of death for male smokers was 1.58 (95% CI = 1.41-1.95; p < .001), adjusted for age and education. Across all FI values, female smokers and male nonsmokers had comparable survival rates. CONCLUSION: Smoking was associated with an increased rate of both worsening health and mortality. At all levels of health status, as defined by deficit accumulation, women who smoked lost the survival advantage conferred by their sex. [ABSTRACT FROM AUTHOR]

Background. Smoking is common in China, where the population is aging rapidly. This study evaluated the relationship between smoking and frailty and their joint association with health and survival in older Chinese men and women. Methods. Data came from the Beijing Longitudinal Study of Aging, a representative cohort study with a 15-year follow-up. Community-dwelling people (n = 3257) aged more than 55 years at baseline were followed between 1992 and 2007, during which time 51% died. A frailty index (FI) was constructed from 28 self-reported health deficits. Results. Almost half (1,485 people; 45.6%) of the participants reported smoking at baseline (66.8% men, 25.3% women). On average, male smokers were frailer (FI = 0.17±0.13) than male nonsmokers (FI = 0.13±0.10; p = .038). No such differences were seen in women. Men who smoked had the lowest survival probability; female nonsmokers had the highest. Compared with female nonsmokers, the risk of death for male smokers was 1.58 (95% CI = 1.41–1.95; p < .001), adjusted for age and education. Across all FI values, female smokers and male nonsmokers had comparable survival rates. Conclusion. Smoking was associated with an increased rate of both worsening health and mortality. At all levels of health status, as defined by deficit accumulation, women who smoked lost the survival advantage conferred by their sex. [ABSTRACT FROM PUBLISHER]