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1.  A Frailty Instrument for primary care: findings from the Survey of Health, Ageing and Retirement in Europe (SHARE) 
BMC Geriatrics  2010;10:57.
A frailty paradigm would be useful in primary care to identify older people at risk, but appropriate metrics at that level are lacking. We created and validated a simple instrument for frailty screening in Europeans aged ≥50. Our study is based on the first wave of the Survey of Health, Ageing and Retirement in Europe (SHARE,, a large population-based survey conducted in 2004-2005 in twelve European countries.
Subjects: SHARE Wave 1 respondents (17,304 females and 13,811 males). Measures: five SHARE variables approximating Fried's frailty definition. Analyses (for each gender): 1) estimation of a discreet factor (DFactor) model based on the frailty variables using LatentGOLD®. A single DFactor with three ordered levels or latent classes (i.e. non-frail, pre-frail and frail) was modelled; 2) the latent classes were characterised against a biopsychosocial range of Wave 1 variables; 3) the prospective mortality risk (unadjusted and age-adjusted) for each frailty class was established on those subjects with known mortality status at Wave 2 (2007-2008) (11,384 females and 9,163 males); 4) two web-based calculators were created for easy retrieval of a subject's frailty class given any five measurements.
Females: the DFactor model included 15,578 cases (standard R2 = 0.61). All five frailty indicators discriminated well (p < 0.001) between the three classes: non-frail (N = 10,420; 66.9%), pre-frail (N = 4,025; 25.8%), and frail (N = 1,133; 7.3%). Relative to the non-frail class, the age-adjusted Odds Ratio (with 95% Confidence Interval) for mortality at Wave 2 was 2.1 (1.4 - 3.0) in the pre-frail and 4.8 (3.1 - 7.4) in the frail. Males: 12,783 cases (standard R2 = 0.61, all frailty indicators had p < 0.001): non-frail (N = 10,517; 82.3%), pre-frail (N = 1,871; 14.6%), and frail (N = 395; 3.1%); age-adjusted OR (95% CI) for mortality: 3.0 (2.3 - 4.0) in the pre-frail, 6.9 (4.7 - 10.2) in the frail.
The SHARE Frailty Instrument has sufficient construct and predictive validity, and is readily and freely accessible via web calculators. To our knowledge, SHARE-FI represents the first European research effort towards a common frailty language at the community level.
PMCID: PMC2939541  PMID: 20731877
2.  Screening for frailty phenotype with objectively-measured physical activity in a west Japanese suburban community: evidence from the Sasaguri Genkimon Study 
BMC Geriatrics  2015;15:36.
The low physical activity domain of the frailty phenotype has been assessed with various self-reported questionnaires, which are prone to possible recall bias and a lack of diagnostic accuracy. The primary purpose of this study was to define the low physical activity domain of the frailty phenotype using accelerometer-based measurement and to evaluate the internal construct validity among older community-dwellers. Secondly, we examined potential correlates of frailty in this population.
We conducted a cross-sectional study of 1,527 community-dwelling older men and women aged 65 and over. Data were drawn from the baseline survey of the Sasaguri Genkimon Study, a cohort study carried out in a west Japanese suburban community. Frailty phenotypes were defined by the following five components: unintentional weight loss, low grip strength, exhaustion, slow gait speed, and low physical activity. Of these criteria, physical activity was objectively measured with a tri-axial accelerometer. To confirm our measure’s internal validity, we performed a latent class analysis (LCA) to assess whether the five components could aggregate statistically into a syndrome. We examined the correlates of frailty using multiple stepwise logistic regression models.
The estimated prevalence of frailty was 9.3% (95% confidence intervals, CI, 8.4-11.2); 43.9% were pre-frail (95% CI, 41.5-46.4). The percentage of low physical activity was 19.5%. Objectively-assessed physical activity and other components aggregated statistically into a syndrome. Overall, increased age, poorer self-perceived health, depressive and anxiety symptoms, not consuming alcohol, no engagement in social activities, and cognitive impairment were associated with increased odds of frailty status, independent of co-morbidities.
This study confirmed the internal construct validity of the frailty phenotype that defined the low energy expenditure domain with the objective measurement of physical activity. Accelerometry may potentially standardize the measurement of low physical activity and improve the diagnostic accuracy of the frailty phenotype criteria in primary care setting. The potential role of factors associated with frailty merits further studies to explore their clinical application.
Electronic supplementary material
The online version of this article (doi:10.1186/s12877-015-0037-9) contains supplementary material, which is available to authorized users.
PMCID: PMC4391124  PMID: 25887474
Frail older people; Aging; Prevalence; Accelerometer; Community health
3.  Oral health conditions and frailty in Mexican community-dwelling elderly: a cross sectional analysis 
BMC Public Health  2012;12:773.
Oral health is an important component of general well-being for the elderly. Oral health-related problems include loss of teeth, nonfunctional removable dental prostheses, lesions of the oral mucosa, periodontitis, and root caries. They affect food selection, speaking ability, mastication, social relations, and quality of life. Frailty is a geriatric syndrome that confers vulnerability to negative health-related outcomes. The association between oral health and frailty has not been explored thoroughly. This study sought to identify associations between the presence of some oral health conditions, and frailty status among Mexican community-dwelling elderly.
Analysis of baseline data of the Mexican Study of Nutritional and Psychosocial Markers of Frailty, a cohort study carried out in a representative sample of people aged 70 and older residing in one district of Mexico City. Frailty was defined as the presence of three or more of the following five components: weight loss, exhaustion, slowness, weakness, and low physical activity. Oral health variables included self-perception of oral health compared with others of the same age; utilization of dental services during the last year, number of teeth, dental condition (edentate, partially edentate, or completely dentate), utilization and functionality of removable partial or complete dentures, severe periodontitis, self-reported chewing problems and xerostomia. Covariates included were gender, age, years of education, cognitive performance, smoking status, recent falls, hospitalization, number of drugs, and comorbidity. The association between frailty and dental variables was determined performing a multivariate logistic regression analysis. Final models were adjusted by socio-demographic and health factors
Of the 838 participants examined, 699 had the information needed to establish the criteria for diagnosis of frailty. Those who had a higher probability of being frail included women (OR = 1.9), those who reported myocardial infarction (OR = 3.8), urinary incontinence (OR = 2.7), those who rated their oral health worse than others (OR = 3.2), and those who did not use dental services (OR = 2.1). For each additional year of age and each additional drug consumed, the probability of being frail increased 10% and 30%, respectively.
Utilization of dental services and self-perception of oral health were associated with a higher probability of being frail.
PMCID: PMC3490998  PMID: 22971075
Elderly; Oral health; Frailty syndrome; Utilization of dental services
4.  Fried phenotype of frailty: cross-sectional comparison of three frailty stages on various health domains 
BMC Geriatrics  2015;15:77.
The population ageing in most Western countries leads to a larger number of frail older people. These frail people are at an increased risk of negative health outcomes, such as functional decline, falls, institutionalisation and mortality. Many approaches are available for identifying frailty among older people. Researchers most often use Fried and colleagues’ description of the frailty phenotype. The authors describe five physical criteria. Other researchers prefer a combination of measurements in the social, psychological and/or physical domains. The aim of this study is to describe the levels of social, psychological and physical functioning according to Fried’s frailty stages using a large cohort of Dutch community-dwelling older people.
There were 8,684 community-dwelling older people (65+) who participated in this cross-sectional study. Based on the five Fried frailty criteria (weight loss, exhaustion, low physical activity, slowness, weakness), the participants were divided into three stages: non-frail (score 0), pre-frail (score 1–2) and frail (score 3–5). These stages were related to scores in the social (social network type, informal care use, loneliness), psychological (psychological distress, mastery, self-management) and physical (chronic diseases, GARS IADL-disability, OECD disability) domains.
63.2 % of the participants was non-frail, 28.1 % pre-frail and 8.7 % frail. When comparing the three stages of frailty, frail people appeared to be older, were more likely to be female, were more often unmarried or living alone, and had a lower level of education compared to their pre-frail and non-frail counterparts. The difference between the scores in the social, psychological and physical domains were statistically significant between the three frailty stages. The most preferable scores came from the non-frail group, and least preferable scores were from the frail group. For example use of informal care: non-frail 3.9 %, pre-frail 23.8 %, frail 60.6 %, and GARS IADL-disability mean scores: non-frail 9.2, pre-frail 13.0, frail 19.7.
When older people were categorised according to the three frailty stages, as described by Fried and colleagues, there were statistically significant differences in the level of social, psychological and physical functioning between the non-frail, pre-frail and frail persons. Non-frail participants had consistently more preferable scores compared to the frail participants. This indicated that the Fried frailty criteria could help healthcare professionals identify and treat frail older people in an efficient way, and provide indications for problems in other domains.
PMCID: PMC4496916  PMID: 26155837
Frailty; Frailty phenotype; Frailty stages; Functional abilities of older persons
5.  Are depression and frailty overlapping syndromes in mid- and late-life? A latent variable analysis 
Depression and frailty both predict disability and morbidity in later life. However, it is unclear to what extent these common geriatric syndromes represent overlapping constructs.
To examine the joint relationship between the constructs of depression and frailty.
Data come from 2004/5 wave of the Baltimore Epidemiologic Catchment Area Study and analysis is limited to participants aged 40 and older with complete data on frailty and depression indicators (N = 683). Depression was measured using the Diagnostic Interview Schedule and frailty was indexed by modified Fried criteria. A series of confirmatory latent class analyses (LCA) were used to assess the degree to which depression and frailty syndromes identify the same populations. A latent Kappa coefficient (Кl) was also estimated between the constructs.
Confirmatory LCA indicated that depression and frailty represent distinct syndromes rather than a single construct. The joint modeling of the two constructs supported a three class solution for depression and two class solution for frailty, with 2.9% categorized as severe depression, 19.4% as mild depression, and 77.7% as not depressed, and 21.1% categorized as frail and 78.9% as not frail. The chance-corrected agreement statistic indicated moderate correspondence between the depression and frailty constructs (Кl: 66, 95% CI: 0.58 – 0.74).
Results suggest that depression and frailty are interrelated concepts, yet their operational criteria identify substantively overlapping subpopulations. These findings have implications for understanding factors that contribute to the etiology and prognosis of depression and frailty in later life.
PMCID: PMC3424389  PMID: 23567406
depression; frailty; latent class analysis; aging
6.  Social Vulnerability, Frailty and Mortality in Elderly People 
PLoS ONE  2008;3(5):e2232.
Social vulnerability is related to the health of elderly people, but its measurement and relationship to frailty are controversial. The aims of the present study were to operationalize social vulnerability according to a deficit accumulation approach, to compare social vulnerability and frailty, and to study social vulnerability in relation to mortality.
Methods and Findings
This is a secondary analysis of community-dwelling elderly people in two cohort studies, the Canadian Study of Health and Aging (CSHA, 1996/7–2001/2; N = 3707) and the National Population Health Survey (NPHS, 1994–2002; N = 2648). Social vulnerability index measures that used self-reported items (23 in NPHS, 40 in CSHA) were constructed. Each measure ranges from 0 (no vulnerability) to 1 (maximum vulnerability). The primary outcome measure was mortality over five (CHSA) or eight (NPHS) years. Associations with age, sex, and frailty (as measured by an analogously constructed frailty index) were also studied. All individuals had some degree of social vulnerability. Women had higher social vulnerability than men, and vulnerability increased with age. Frailty and social vulnerability were moderately correlated. Adjusting for age, sex, and frailty, each additional social ‘deficit’ was associated with an increased odds of mortality (5 years in CSHA, odds ratio = 1.05, 95% confidence interval: 1.02–1.07; 8 years in the NPHS, odds ratio = 1.08, 95% confidence interval: 1.03–1.14). We identified a meaningful survival gradient across quartiles of social vulnerability, and although women had better survival than men, survival for women with high social vulnerability was equivalent to that of men with low vulnerability.
Social vulnerability is reproducibly related to individual frailty/fitness, but distinct from it. Greater social vulnerability is associated with mortality in older adults. Further study on the measurement and operationalization of social vulnerability, and of its relationships to other important health outcomes, is warranted.
PMCID: PMC2375054  PMID: 18493324
7.  Social Support, Stressors, and Frailty Among Older Mexican American Adults 
There is little research on the effects of stressors and social support on frailty. Older Mexican Americans, in particular, are at higher risk of medical conditions, such as diabetes, that could contribute to frailty. Given that the Mexican American population is rapidly growing in the United States, it is important to determine whether there are modifiable social factors related to frailty in this older group.
To address the influence of social support and stressors on frailty among older Mexican Americans, we utilized five waves of the Hispanic Established Populations for the Epidemiologic Study of the Elderly (Hispanic EPESE) to examine the impact of stressors and social support on frailty over a 12-year period. Using a modified version of the Fried and Walston Frailty Index, we estimated the effects of social support and stressors on frailty over time using trajectory modeling (SAS 9.2, PROC TRAJ).
We first grouped respondents according to one of three trajectories: low, progressive moderate, and progressive high frailty. Second, we found that the effects of stressors and social support on frailty varied by trajectory and by type of stressor. Health-related stressors and financial strain were related to increases in frailty over time, whereas social support was related to less-steep increases in frailty.
Frailty has been hypothesized to reflect age-related physiological vulnerability to stressors, and the analyses presented indicate partial support for this hypothesis in an older sample of Mexican Americans. Future research needs to incorporate measures of stressors and social support in examining those who become frail, especially in minority populations.
PMCID: PMC3478725  PMID: 23009957
Functional health status; Minority aging (race/ethnicity); Social support; Stress
8.  Gender Differences in the Construct Overlap of Frailty and Depression: Evidence from the Health and Retirement Study 
To determine the degree of diagnostic overlap between frailty and depression and investigate whether gender differences in symptom endorsement influence this overlap.
Cross-sectional latent class analysis.
Data come from the 2008 wave of the Health and Retirement Study, a nationally-representative longitudinal survey of health characteristics among older adults.
Community-dwelling adults aged 65 and older completing a generalhealth questionnaire and consenting to physical measurements (N=3,665).
Frailty was measured using criteria developed in the Cardiovascular Health Study and depressive symptoms were measured using the 8-item Center for Epidemiologic Studies Depression scale.
Frailty and depression were best modelled as two distinct but highly correlated constructs with 3-classes and 4-classes of symptom response respectively. Measurement overlap was high among both men and women. Approximately 73% of individuals with severe depressive symptoms, and 86% of individuals with primarily somatic depressive symptoms, were categorized as concurrently frail. The degree of construct overlap between depression and frailty did not significantly vary by gender, but women were significantly more likely to endorse all frailty and depressive symptoms.
Measures of depression and frailty identify substantially overlapping populations of older men and women. More frequent endorsement of depressive symptoms, but not differential endorsement of somatic symptoms may contribute to the higher prevalence of frailty among women. The symptom of exhaustion is particularly important to the correlation between these two conditions. Findings will inform efforts by clinicians and researchers to refine the definition of geriatric syndromes like frailty and to develop effective interventions.
PMCID: PMC4112955  PMID: 24576097
9.  Frailty 
Canadian Family Physician  2015;61(3):227-231.
To help family physicians better recognize frailty and its implications for managing elderly patients.
Sources of information
PubMed-MEDLINE was searched from 1990 to 2013. The search was restricted to English-language articles using the following groups of MeSH headings and key words: frail elderly, frail, frailty; aged, geriatrics, geriatric assessment, health services for the aged; and primary health care, community health services, and family practice.
Main message
Frailty is common, particularly in elderly persons with complex chronic conditions such as heart failure and chronic obstructive pulmonary disease. Emerging evidence demonstrates the value of frailty as a predictor of adverse outcomes in older persons. While there is currently a lack of consensus as to how best to assess and diagnose frailty in primary care practice, individual markers of frailty such as low gait speed offer a promising feasible means of screening for frailty. Identification of frailty in primary care might provide an opportunity to delay the progression of frailty through proactive interventions such as exercise, and awareness of frailty can guide appropriate counseling and anticipatory preventive measures for patients when considering medical interventions. Recognition of frailty might also help identify and optimize the management of coexisting conditions that might contribute to or be affected by frailty. Further research should be directed at identifying feasible and effective ways to appropriately assess and manage these vulnerable patients at the primary care level.
Despite its importance, little attention has been given to the concept of frailty in family medicine. Frailty is easily overlooked because its manifestations can be subtle, slowly progressive, and thus dismissed as normal aging; and physician training has been focused on specific medical diseases rather than overall vulnerability. For primary care physicians, recognition of frailty might help them provide appropriate counseling to patients and family members about the risks of medical interventions.
PMCID: PMC4369632  PMID: 25767167
10.  Transitions in Frailty Status in Older Adults in Relation to Mobility: A Multi-State Modeling Approach Employing a Deficit Count 
To investigate how changes in frailty status and mortality risk relate to baseline frailty state, mobility performance, age and sex.
The Yale Precipitating Events Project, a cohort study based in New Haven CT.
754 community-dwelling people, aged 70+ years at baseline followed-up at 18, 36 and 54 months.
Frailty status, assessed at 18-month intervals, was defined by a frailty index, as the number of deficits in 36 health variables. Mobility was defined as the time in seconds on the rapid gait test, where participants walked back and forth over a 20-ft course as quickly as possible. Multi-state transition probabilities were calculated with baseline frailty, mobility, age and sex estimated by Poisson and logistic regressions in survivors and those who died, respectively.
In multivariable analyses, baseline frailty status and age were significantly associated with changes in frailty status and the risk of death, while mobility was significantly associated with the former, but not with mortality. At all values of the frailty index, compared to those with poor mobility, participants with better mobility were more likely to remain stable or to improve. For example, at 54 months, 20.6% (95% confidence interval (CI) =16–25.2) of participants with poor mobility had the same or fewer deficits compared to 32.4% (95% CI=27.9–36.9) of those with better mobility.
A multi-state transition model effectively measured the probability of changes in frailty status and in the risk of death. Mobility, age and baseline frailty were significant factors in frailty state transitions.
PMCID: PMC3125634  PMID: 21391943
frailty; Frailty Index; mortality; aging; mobility; multistate model
11.  Cohort differences in the levels and trajectories of frailty among older people in England 
The level of frailty in the older population across age cohorts and how this changes is a factor in determining future care costs and may also influence the extent of socioeconomic and gender inequalities in frailty.
We model cohort-specific trajectories in frailty among the community dwelling population older than 50 years, using five waves (2002–2010) of the English Longitudinal Study of Ageing. We stratify our analysis by wealth and gender and use a frailty index, based on accumulation of ‘deficits’.
For males and females between the ages of 50 and 70 in 2002, frailty trajectories for adjacent age cohorts converge. However, levels of frailty are higher in recent compared with earlier cohorts at the older ages (for cohorts aged over 70 in 2002). These cohort differences are largest in the poorest wealth group, while for the most affluent, frailty trajectories overlap across all adjacent cohorts suggesting no change across cohorts.
A key driver of the cohort differences in frailty that we observe is likely to be increased survival of frail individuals. Importantly, this paper illustrates that the social conditions experienced across the wealth distribution impacts on the rate of deficit accumulation in older populations. Our results on trajectories of frailty between 2002 and 2010 are pessimistic and, in the context of rising life expectancies, suggest that poorer older people in particular spend additional years of life in a frail state.
PMCID: PMC4392235  PMID: 25646207
12.  Prevalence and correlates of frailty among older adults: findings from the German health interview and examination survey 
BMC Geriatrics  2015;15:22.
Despite having the third highest proportion of people aged 60 years and older in the world, Germany has been recently reported as having the lowest prevalence of frailty of 15 European countries. The objective of the study is to describe the prevalence of frailty in a large nationwide population-based sample and examine associations with sociodemographic, social support and health characteristics.
We performed a cross-sectional analysis of the first wave of the German Health Interview and Examination Survey for Adults (DEGS1) conducted 2008–2011. Participants were 1843 community-dwelling people aged 65–79 years. Frailty and pre-frailty were defined, according to modified Fried criteria, as 3 and more or 1–2 respectively, of the following: exhaustion, low weight, low physical activity, low walking speed and low grip strength. The Oslo-3 item Social Support Scale (OSS-3) was used. Patient Health Questionnaire (PHQ-9) measured depressive symptoms and the Digit Symbol Substitution Test (DSST) measured cognition. Associations between participants’ characteristics and frailty status were examined using unadjusted and adjusted multinomial logistic regression models estimating relative risk ratios (RRR) of frailty and pre-frailty.
The prevalence of frailty among women was 2.8% (CI 1.8-4.3) and pre-frailty 40.4% (CI 36.3-44.7) and among men was 2.3% (CI 1.3-4.1) and 36.9% (CI 32.7-41.3) respectively. Independent determinants of frailty, from unadjusted models, included older age, low socioeconomic status, poor social support, lower cognitive function and a history of falls. In adjusted models current depressive symptoms (RRR 12.86, CI 4.47-37.03), polypharmacy (RRR 7.78, CI 2.92-20.72) and poor hearing (RRR 5.38, CI 2.17-13.35) were statistically significantly associated with frailty.
Frailty prevalence is relatively low among community-dwelling older adults in Germany. Modifiable characteristics like low physical activity provide relevant targets for individual and population-level frailty detection and intervention strategies.
PMCID: PMC4357063  PMID: 25879568
Frailty; Aging; Elderly; Prevalence; Community-dwelling; Germany
13.  Comparing frailty measures in their ability to predict adverse outcome among older residents of assisted living 
BMC Geriatrics  2012;12:56.
Few studies have directly compared the competing approaches to identifying frailty in more vulnerable older populations. We examined the ability of two versions of a frailty index (43 vs. 83 items), the Cardiovascular Health Study (CHS) frailty criteria, and the CHESS scale to accurately predict the occurrence of three outcomes among Assisted Living (AL) residents followed over one year.
The three frailty measures and the CHESS scale were derived from assessment items completed among 1,066 AL residents (aged 65+) participating in the Alberta Continuing Care Epidemiological Studies (ACCES). Adjusted risks of one-year mortality, hospitalization and long-term care placement were estimated for those categorized as frail or pre-frail compared with non-frail (or at high/intermediate vs. low risk on CHESS). The area under the ROC curve (AUC) was calculated for select models to assess the predictive accuracy of the different frailty measures and CHESS scale in relation to the three outcomes examined.
Frail subjects defined by the three approaches and those at high risk for decline on CHESS showed a statistically significant increased risk for death and long-term care placement compared with those categorized as either not frail or at low risk for decline. The risk estimates for hospitalization associated with the frailty measures and CHESS were generally weaker with one of the frailty indices (43 items) showing no significant association. For death and long-term care placement, the addition of frailty (however derived) or CHESS significantly improved on the AUC obtained with a model including only age, sex and co-morbidity, though the magnitude of improvement was sometimes small. The different frailty/risk models did not differ significantly from each other in predicting mortality or hospitalization; however, one of the frailty indices (83 items) showed significantly better performance over the other measures in predicting long-term care placement.
Using different approaches, varying degrees of frailty were detected within the AL population. The various approaches to defining frailty were generally more similar than dissimilar with regard to predictive accuracy with some exceptions. The clinical implications and opportunities of detecting frailty in more vulnerable older adults require further investigation.
PMCID: PMC3573890  PMID: 22978265
Frailty; Predictive accuracy; Agreement; Assisted living
14.  A comparison of Dutch frail older adults in 1998 and 2008: prevalences and determinants 
Society is facing a growing number of older people. With the increase of older people an increase in number of frail persons is expected. But will the increase in number of frail persons parallel the increase of the number of older adults? Or are the features of older adults changing in time and are these changes reducing or amplifying the increase of frail older adults?
To present the differences in prevalence of frail older persons in 1998 and in 2008 and the influence of socio-demographic and health features on the difference between these two cohorts.
The data were collected in the context of the Longitudinal Aging Study Amsterdam (LASA). For this particular study we selected community dwelling respondents aged 65–88 years who had complete data in 1995 or 2008. Frailty was composed out of seven markers: BMI, cognitive functioning, grip strength, tiredness, vision and hearing problems and physical activity. Two cohorts, 1998 and 2008, were compared and the relative numbers of frail older adults in both cohorts were calculated. Next the association of different socio-demographic and health features with frailty was examined.
Preliminary results show a decrease in the prevalence of frail older adults from 18.5% in 1998 to 9.9% in 2008. The prevalence of frail people in 2008 for all age groups decreased compared to 1995 but in particular for the youngest age groups. In addition, the decrease in frail women is more amplified than in men. For all the markers used in defining frailty an improvement is seen for the population in 2008. Multivariate analyses will show in what degree cohort differences in frailty are related to cohort differences in education, income, co-morbidity, partner status, social network, mastery, alcohol use and smoking.
The prevalence of frail elderly in 2008 has declined compared to 1998. This can be explained by improvements in all markers of frailty. Analyses (yet to be completed) will show the influence of socio-demographic and health features.
PMCID: PMC3617773
frail older persons; prevalence; influence of socio-demographic and health features; markers
15.  Frailty, HIV Infection, and Mortality in an Aging Cohort of Injection Drug Users 
PLoS ONE  2013;8(1):e54910.
Frailty is associated with morbidity and premature mortality among elderly HIV-uninfected adults, but the determinants and consequences of frailty in HIV-infected populations remain unclear. We evaluated the correlates of frailty, and the impact of frailty on mortality in a cohort of aging injection drug users (IDUs).
Frailty was assessed using standard criteria among HIV-infected and uninfected IDUs in 6-month intervals from 2005 to 2008. Generalized linear mixed-model analyses assessed correlates of frailty. Cox proportional hazards models estimated risk for all-cause mortality.
Of 1230 participants at baseline, the median age was 48 years and 29% were HIV-infected; the frailty prevalence was 12.3%. In multivariable analysis of 3,365 frailty measures, HIV-infected IDUs had an increased likelihood of frailty (OR, 1.66; 95% CI, 1.24–2.21) compared to HIV-uninfected IDUs; the association was strongest (OR, 2.37; 95% CI, 1.62–3.48) among HIV-infected IDUs with advanced HIV disease (CD4<350 cells/mm3 and detectable HIV RNA). No significant association was seen with less advanced disease. Sociodemographic factors, comorbidity, depressive symptoms, and prescription drug abuse were also independently associated with frailty. Mortality risk was increased with frailty alone (HR 2.63, 95% CI, 1.23–5.66), HIV infection alone (HR 3.29, 95% CI, 1.85–5.88), and being both HIV-infected and frail (HR, 7.06; 95%CI 3.49–14.3).
Frailty was strongly associated with advanced HIV disease, but IDUs with well-controlled HIV had a similar prevalence to HIV-uninfected IDUs. Frailty was independently associated with mortality, with a marked increase in mortality risk for IDUs with both frailty and HIV infection.
PMCID: PMC3561408  PMID: 23382997
16.  A Frailty Instrument for primary care for those aged 75 years or more: findings from the Survey of Health, Ageing and Retirement in Europe, a longitudinal population-based cohort study (SHARE-FI75+) 
BMJ Open  2014;4(12):e006645.
To create and validate a frailty assessment tool for community-dwelling adults aged ≥75 years.
Longitudinal, population-based study.
The Survey of Health, Ageing and Retirement in Europe (SHARE).
4001 women and 3057 men aged ≥75 years from the second wave of SHARE. 3325 women and 2587 men had complete information for the frailty indicators: fatigue, low appetite, weakness, observed gait (walking without help, walking with help, chairbound/bedbound, unobserved) and low physical activity.
Main outcome measures
The internal validity of the frailty indicators was tested with latent class analysis, by modelling an underlying variable with three ordered categories. The predictive validity of the frailty classification was tested against 2-year mortality and 4-year disability. The mortality prediction of SHARE-FI75+ was compared with that of previously operationalised frailty scales in SHARE (SHARE-FI, 70-item index, phenotype, FRAIL).
In both genders, all frailty indicators significantly aggregated into a three-category ordinal latent variable. After adjusting for baseline age, comorbidity and basic activities of daily living (BADL) disability, the frail had an OR for 2-year mortality of 2.2 (95% CI 1.2 to 3.8) in women and 4.2 (2.6 to 6.8) in men. The mortality prediction of SHARE-FI75+ was similar to that of the other SHARE frailty scales. By wave 4, 49% of frail women (78 of 159) had at least one more limitation with BADL (compared with 18% of non-frail, 125 of 684; p<0.001); in men, these proportions were 39% (26 of 66) and 18% (110 of 621), respectively (p<0.001). A calculator is supplied for point-of-care use, which automatically replicates the frailty classification for any given measurements.
SHARE-FI75+ could help frailty case finding in primary care and provide a focus for personalised community interventions. Further validation in trials and clinical programmes is needed.
PMCID: PMC4275665  PMID: 25537787
Frail Elderly; Screening; Geriatric Assessment; Primary Health Care; Validation Studies; Longitudinal Survey
17.  Prospective association of the SHARE-operationalized frailty phenotype with adverse health outcomes: evidence from 60+ community-dwelling Europeans living in 11 countries 
BMC Geriatrics  2013;13:3.
Among the many definitions of frailty, the frailty phenotype defined by Fried et al. is one of few constructs that has been repeatedly validated: first in the Cardiovascular Health Study (CHS) and subsequently in other large cohorts in the North America. In Europe, the Survey of Health, Aging and Retirement in Europe (SHARE) is a gold mine of individual, economic and health information that can provide insight into better understanding of frailty across diverse population settings. A recent adaptation of the original five CHS-frailty criteria was proposed to make use of SHARE data and measure frailty in the European population. To test the validity of the SHARE operationalized frailty phenotype, this study aims to evaluate its prospective association with adverse health outcomes.
Data are from 11,015 community-dwelling men and women aged 60+ participating in wave 1 and 2 of the Survey of Health, Aging and Retirement in Europe, a population-based survey. Multivariate logistic regression analyses were used to assess the 2-year follow up effect of SHARE-operationalized frailty phenotype on the incidence of disability (disability-free at baseline) and on worsening disability and morbidity, adjusting for age, sex, income and baseline morbidity and disability.
At 2-year follow up, frail individuals were at increased risk for: developing mobility (OR 3.07, 95% CI, 1.02-9.36), IADL (OR 5.52, 95% CI, 3.76-8.10) and BADL (OR 5.13, 95% CI, 3.53-7.44) disability; worsening mobility (OR 2.94, 95% CI, 2.19- 3.93) IADL (OR 4.43, 95% CI, 3.19-6.15) and BADL disability (OR 4.53, 95% CI, 3.14-6.54); and worsening morbidity (OR 1.77, 95% CI, 1.35-2.32). These associations were significant even among the prefrail, but with a lower magnitude of effect.
The SHARE-operationalized frailty phenotype is significantly associated with all tested health outcomes independent of baseline morbidity and disability in community-dwelling men and women aged 60 and older living in Europe. The robustness of results validate the use of this phenotype in the SHARE survey for future research on frailty in Europe.
PMCID: PMC3585820  PMID: 23286928
Frailty phenotype; Validation; Adverse outcomes; Population survey; SHARE; BADL disability; IADL disability; Morbidity
18.  Frailty and Its Impact on Health-Related Quality of Life: A Cross-Sectional Study on Elder Community-Dwelling Preventive Health Service Users 
PLoS ONE  2012;7(5):e38079.
The purpose of this study was to identify the incidence of frailty and to investigate the relationship between frailty status and health-related quality of life (HRQoL) in the community-dwelling elderly population who utilize preventive health services.
People aged 65 years and older who visited a medical center in Taipei City from March to August in 2011 for an annual routine check-up provided by the National Health Insurance were eligible. A total of 374 eligible elderly adults without cognitive impairment had a mean age of 74.6±6.3 years. Frailty status was determined according to the Fried frailty criteria. HRQoL was measured with Short Form-36 (SF-36). Multiple regression analyses examined the relationship between frailty status and the two summary scales of SF-36. Models were adjusted for the participants' sociodemographic and health status.
After adjusting for sociodemographic and health-related covariables, frailty was found to be more significantly associated (p<0.001) with lower scores on both physical and mental health-related quality of life summary scales compared with robustness. For the frailty phenotypes, slowness represented the major contributing factor in the physical component scale of SF-36, and exhaustion was the primary contributing factor in the mental component scale.
The status of frailty is closely associated with HRQoL in elderly Taiwanese preventive health service users. The impacts of frailty phenotypes on physical and mental aspects of HRQoL differ.
PMCID: PMC3360631  PMID: 22662268
19.  Exploring the relationship between national economic indicators and relative fitness and frailty in middle-aged and older Europeans 
Age and Ageing  2013;42(5):614-619.
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.
PMCID: PMC3745086  PMID: 23443511
ageing; frailty; Europe; SHARE; older people
20.  Frailty and the prediction of dependence and mortality in low- and middle-income countries: a 10/66 population-based cohort study 
BMC Medicine  2015;13:138.
In countries with high incomes, frailty indicators predict adverse outcomes in older people, despite a lack of consensus on definition or measurement. We tested the predictive validity of physical and multidimensional frailty phenotypes in settings in Latin America, India, and China.
Population-based cohort studies were conducted in catchment area sites in Cuba, Dominican Republic, Venezuela, Mexico, Peru, India, and China. Seven frailty indicators, namely gait speed, self-reported exhaustion, weight loss, low energy expenditure, undernutrition, cognitive, and sensory impairment were assessed to estimate frailty phenotypes. Mortality and onset of dependence were ascertained after a median of 3.9 years.
Overall, 13,924 older people were assessed at baseline, with 47,438 person-years follow-up for mortality and 30,689 for dependence. Both frailty phenotypes predicted the onset of dependence and mortality, even adjusting for chronic diseases and disability, with little heterogeneity of effect among sites. However, population attributable fractions (PAF) summarising etiologic force were highest for the aggregate effect of the individual indicators, as opposed to either the number of indicators or the dichotomised frailty phenotypes. The aggregate of all seven indicators provided the best overall prediction (weighted mean PAF 41.8 % for dependence and 38.3 % for mortality). While weight loss, underactivity, slow walking speed, and cognitive impairment predicted both outcomes, whereas undernutrition predicted only mortality and sensory impairment only dependence. Exhaustion predicted neither outcome.
Simply assessed frailty indicators identify older people at risk of dependence and mortality, beyond information provided by chronic disease diagnoses and disability. Frailty is likely to be multidimensional. A better understanding of the construct and pathways to adverse outcomes could inform multidimensional assessment and intervention to prevent or manage dependence in frail older people, with potential to add life to years, and years to life.
PMCID: PMC4481121  PMID: 26063168
Aged; Frailty; Developing countries; Disability; Geriatric assessment; Epidemiology; Long-term care; Mortality
21.  Determinants of frailty: the added value of assessing medication 
This study aims to analyze which determinants predict frailty in general and each frailty domain (physical, psychological, and social), considering the integral conceptual model of frailty, and particularly to examine the contribution of medication in this prediction. A cross-sectional study was designed using a non-probabilistic sample of 252 community-dwelling elderly from three Portuguese cities. Frailty and determinants of frailty were assessed with the Tilburg Frailty Indicator. The amount and type of different daily-consumed medication were also examined. Hierarchical regression analysis were conducted. The mean age of the participants was 79.2 years (±7.3), and most of them were women (75.8%), widowed (55.6%) and with a low educational level (0–4 years: 63.9%). In this study, determinants explained 46% of the variance of total frailty, and 39.8, 25.3, and 27.7% of physical, psychological, and social frailty respectively. Age, gender, income, death of a loved one in the past year, lifestyle, satisfaction with living environment and self-reported comorbidity predicted total frailty, while each frailty domain was associated with a different set of determinants. The number of daily-consumed drugs was independently associated with physical frailty, and the consumption of medication for the cardiovascular system and for the blood and blood-forming organs explained part of the variance of total and physical frailty. The adverse effects of polymedication and its direct link with the level of comorbidities could explain the independent contribution of the amount of prescribed drugs to frailty prediction. On the other hand, findings in regard to medication type provide further evidence of the association of frailty with cardiovascular risk. In the present study, a significant part of frailty was predicted, and the different contributions of each determinant to frailty domains highlight the relevance of the integral model of frailty. The added value of a simple assessment of medication was considerable, and it should be taken into account for effective identification of frailty.
PMCID: PMC4404866  PMID: 25954195
elderly; frailty; determinants; comorbidity; medication
22.  Changes in relative fitness and frailty across the adult lifespan: evidence from the Canadian National Population Health Survey 
The prevalence of frailty increases with age in older adults, but frailty is largely unreported for younger adults, where its associated risk is less clear. Furthermore, less is known about how frailty changes over time among younger adults. We estimated the prevalence and outcomes of frailty, in relation to accumulation of deficits, across the adult lifespan.
We analyzed data for community-dwelling respondents (age 15–102 years at baseline) to the longitudinal component of the National Population Health Survey, with seven two-year cycles, beginning 1994–1995. The outcomes were death, use of health services and change in health status, measured in terms of a Frailty Index constructed from 42 self-reported health variables.
The sample consisted of 14 713 respondents (54.2% women). Vital status was known for more than 99% of the respondents. The prevalence of frailty increased with age, from 2.0% (95% confidence interval [CI] 1.7%–2.4%) among those younger than 30 years to 22.4% (95% CI 19.0%–25.8%) for those older than age 65, including 43.7% (95% CI 37.1%–50.8%) for those 85 and older. At all ages, the 160-month mortality rate was lower among relatively fit people than among those who were frail (e.g., 2% v. 16% at age 40; 42% v. 83% at age 75 or older). These relatively fit people tended to remain relatively fit over time. Relative to all other groups, a greater proportion of the most frail people used health services at baseline (28.3%, 95% CI 21.5%–35.5%) and at each follow-up cycle (26.7%, 95% CI 15.4%–28.0%).
Deficits accumulated with age across the adult spectrum. At all ages, a higher Frailty Index was associated with higher mortality and greater use of health care services. At younger ages, recovery to the relatively fittest state was common, but the chance of complete recovery declined with age.
PMCID: PMC3091935  PMID: 21540166
23.  Frailty and 10-year mortality in community-living Mexican American older adults 
Gerontology  2009;55(6):644-651.
The older Hispanic population of the United States is growing rapidly. Hispanic older adults have relatively high risk-profiles for increased morbidity and disability, yet little is known about how the construct of frailty is related to health trajectories in this population.
The purpose of this study was to examine the relationship between frailty and 10-year mortality in older community-dwelling Mexican Americans.
Data were from the Hispanic Established Populations for Epidemiologic Studies of the Elderly and included 1,996 Mexican Americans, aged 65 and older, living in the southwestern U.S. Primary measures included mortality and a 5-item frailty index comprised of weight loss, exhaustion, walking speed, grip strength, and physical activity.
Mean baseline age was 74.5 yrs (sd 6.1) and 58.5% were women. Baseline frailty assessments yielded the following distribution: 44.9% non-frail, 47.3% pre-frail, and 7.8% frail. Overall, 892 (44.7%) participants died during the 10 year study period. Hazard ratios (HR), adjusted for sociodemographic, health, and medical factors, demonstrated increased odds for mortality in the pre-frail (HR = 1.25: CI95% 1.07, 1.46) and frail (HR = 1.81: CI95% 1.41, 2.31) groups compared to the non-frail cohort.
The 5-item frailty index differentiated odds of 10 year mortality in older community-dwelling Mexican Americans. This clinical index has the potential to identify older minorities at risk for poor health outcomes and mortality.
PMCID: PMC2783319  PMID: 19690395
aging; frail elderly; Hispanic Americans; minorities; survival
24.  Frailty and 10-Year Mortality in Community-Living Mexican American Older Adults 
Gerontology  2009;55(6):644-651.
The older Hispanic population of the United States is growing rapidly. Hispanic older adults have relatively high-risk profiles for increased morbidity and disability, yet little is known about how the construct of frailty is related to health trajectories in this population. Objective: The purpose of this study was to examine the relationship between frailty and 10-year mortality in older community-dwelling Mexican Americans.
Data were from the Hispanic Established Populations for Epidemiologic Studies of the Elderly and included 1,996 Mexican Americans, aged 65 and older, living in the southwestern US. Primary measures included mortality and a 5-item frailty index comprised of weight loss, exhaustion, walking speed, grip strength, and physical activity.
Mean baseline age was 74.5 years (SD 6.1) and 58.5% were women. Baseline frailty assessments yielded the following distribution: 44.9% non-frail, 47.3% pre-frail, and 7.8% frail. Overall, 892 (44.7%) participants died during the 10-year study period. Hazard ratios (HR), adjusted for sociodemographic, health, and medical factors, demonstrated increased odds for mortality in the pre-frail (HR = 1.25, 95% confidence interval, CI95%, 1.07–1.46) and frail (HR = 1.81, CI95% 1.41–2.31) groups compared to the non-frail cohort.
The 5-item frailty index differentiated odds of 10-year mortality in older community-dwelling Mexican Americans. This clinical index has the potential to identify older minorities at risk for poor health outcomes and mortality.
PMCID: PMC2783319  PMID: 19690395
Aging; Frail elderly; Hispanic Americans; Minorities; Survival
25.  Reduced Health-Related Quality of Life in Elders with Frailty: A Cross-Sectional Study of Community-Dwelling Elders in Taiwan 
PLoS ONE  2011;6(7):e21841.
Exploring the domains and degrees of health-related quality of life (HRQOL) that are affected by the frailty of elders will help clinicians understand the impact of frailty. This association has not been investigated in community-dwelling elders. Therefore, we examined the domains and degree of HRQOL of elders with frailty in the community in Taiwan.
A total of 933 subjects aged 65 years and over were recruited in 2009 from a metropolitan city in Taiwan. Using an adoption of the Fried criteria, frailty was defined by five components: shrinking, weakness, poor endurance and energy, slowness, and low physical activity level. HRQOL was assessed by the short form 36 (SF-36). The multiple linear regression model was used to test the independent effects of frailty on HRQOL.
After multivariate adjustment, elders without frailty reported significantly better health than did the pre-frail and frail elders on all scales, and the pre-frail elders reported better health than did the frail elders for all scales except the scales of role limitation due to physical and emotional problems and the Mental Component Summary (MCS). The significantly negative differences between frail and robust elders ranged from 3.58 points for the MCS to 22.92 points for the physical functioning scale. The magnitude of the effects of frail components was largest for poor endurance and energy, and next was for slowness. The percentages of the variations of these 10 scales explained by all factors in the models ranged from 11.1% (scale of role limitation due to emotional problems) to 49.1% (scale of bodily pain).
Our study demonstrates that the disabilities in physical health inherent in frailty are linked to a reduction in HRQOL. Such an association between clinical measures and a generic measure of the HRQOL may offer clinicians new information to understand frailty and to conceptualize it within the broader context of disability.
PMCID: PMC3128625  PMID: 21747961

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