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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.
Background
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, http://www.share-project.org), a large population-based survey conducted in 2004-2005 in twelve European countries.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1471-2318-10-57
PMCID: PMC2939541  PMID: 20731877
2.  Frailty, HIV Infection, and Mortality in an Aging Cohort of Injection Drug Users 
PLoS ONE  2013;8(1):e54910.
Background
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).
Methods
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.
Results
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).
Conclusion
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.
doi:10.1371/journal.pone.0054910
PMCID: PMC3561408  PMID: 23382997
3.  Are depression and frailty overlapping syndromes in mid- and late-life? A latent variable analysis 
Background
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.
Objective
To examine the joint relationship between the constructs of depression and frailty.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1016/j.jagp.2012.12.019
PMCID: PMC3424389  PMID: 23567406
depression; frailty; latent class analysis; aging
4.  Oral health conditions and frailty in Mexican community-dwelling elderly: a cross sectional analysis 
BMC Public Health  2012;12:773.
Background
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.
Methods
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
Results
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.
Conclusions
Utilization of dental services and self-perception of oral health were associated with a higher probability of being frail.
doi:10.1186/1471-2458-12-773
PMCID: PMC3490998  PMID: 22971075
Elderly; Oral health; Frailty syndrome; Utilization of dental services
5.  Social Vulnerability, Frailty and Mortality in Elderly People 
PLoS ONE  2008;3(5):e2232.
Background
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.
Conclusions
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.
doi:10.1371/journal.pone.0002232
PMCID: PMC2375054  PMID: 18493324
6.  Social Support, Stressors, and Frailty Among Older Mexican American Adults 
Background.
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.
Method.
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).
Results.
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.
Conclusion.
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.
doi:10.1093/geronb/gbs081
PMCID: PMC3478725  PMID: 23009957
Functional health status; Minority aging (race/ethnicity); Social support; Stress
7.  Transitions in Frailty Status in Older Adults in Relation to Mobility: A Multi-State Modeling Approach Employing a Deficit Count 
OBJECTIVES
To investigate how changes in frailty status and mortality risk relate to baseline frailty state, mobility performance, age and sex.
SETTING
The Yale Precipitating Events Project, a cohort study based in New Haven CT.
PARTICIPANTS
754 community-dwelling people, aged 70+ years at baseline followed-up at 18, 36 and 54 months.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
doi:10.1111/j.1532-5415.2011.03300.x
PMCID: PMC3125634  PMID: 21391943
frailty; Frailty Index; mortality; aging; mobility; multistate model
8.  Frailty among rural elderly adults 
BMC Geriatrics  2014;14:2.
Background
This study aimed to estimate the prevalence and associated factors related to frailty, by Fried criteria, in the elderly population in a rural area in the Andes Mountains, and to analyze the relationship of these with comorbidity and disability.
Methods
A cross-sectional study was undertaken involving 1878 participants 60 years of age and older. The frailty syndrome was diagnosed based on the Fried criteria (weakness, low speed, low physical activity, exhaustion, and weight loss). Variables were grouped as theoretical domains and, along with other potential confounders, were placed into five categories: (a) demographic and socioeconomic status, (b) health status, (c) self-reported functional status, (d) physical performance-based measures, and (e) psychosocial factors. Chi-square, ANOVA, and multinomial logistic regression analyses were used to test the prognostic value of frailty for the outcomes of interest.
Results
The prevalence of frailty was 12.2%. Factors associated with frailty were age, gender, health status variables that included self-perceived health and number of chronic conditions, functional covariate variables that included disability in activities in daily living (ADL), disabilities in instrumental ADL, chair stand time, and psychosocial variables that included depressive symptoms and cognitive impairment. Higher comorbidity and disability was found in frail elderly people. Only a subset of frail elderly people (10%) reported no disease or disability.
Conclusions
A relevant number of elderly persons living in rural areas in the Andes Mountains are frail. The prevalence of frailty is similar to that reported in other populations in the Latin American region. Our results support the use of modified Cardiovascular Health Study criteria to measure frailty in communities other than urban settings. Frailty in this study was strongly associated with comorbidities, and frailty and comorbidity predicted disability.
doi:10.1186/1471-2318-14-2
PMCID: PMC3898393  PMID: 24405584
Frailty; Disability; Prevalence; Colombia
9.  Comparing frailty measures in their ability to predict adverse outcome among older residents of assisted living 
BMC Geriatrics  2012;12:56.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1471-2318-12-56
PMCID: PMC3573890  PMID: 22978265
Frailty; Predictive accuracy; Agreement; Assisted living
10.  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.
Objective
To create and validate a frailty assessment tool for community-dwelling adults aged ≥75 years.
Design
Longitudinal, population-based study.
Setting
The Survey of Health, Ageing and Retirement in Europe (SHARE).
Participants
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).
Results
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.
Conclusions
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.
doi:10.1136/bmjopen-2014-006645
PMCID: PMC4275665  PMID: 25537787
Frail Elderly; Screening; Geriatric Assessment; Primary Health Care; Validation Studies; Longitudinal Survey
11.  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.
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1371/journal.pone.0038079
PMCID: PMC3360631  PMID: 22662268
12.  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.
doi:10.1093/ageing/aft010
PMCID: PMC3745086  PMID: 23443511
ageing; frailty; Europe; SHARE; older people
13.  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.
Purpose
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1371/journal.pone.0021841
PMCID: PMC3128625  PMID: 21747961
14.  A multifactorial interdisciplinary intervention reduces frailty in older people: randomized trial 
BMC Medicine  2013;11:65.
Background
Frailty is a well known and accepted term to clinicians working with older people. The study aim was to determine whether an intervention could reduce frailty and improve mobility.
Methods
We conducted a single center, randomized, controlled trial among older people who were frail in Sydney, Australia. One group received an intervention targeting the identified characteristics of frailty, whereas the comparison group received the usual health care and support services. Outcomes were assessed by raters masked to treatment allocation at 3 and 12 months after study entry. The primary outcomes were frailty as assessed by the Cardiovascular Health Study criteria, and mobility as assessed by the Short Physical Performance Battery. Secondary outcome measures included disability, depressive symptoms and health-related quality of life.
Results
A total of 216 participants (90%) completed the study. Overall, 68% of participants were women and the mean age was 83.3 years (standard deviation, 5.9). In the intention-to-treat analysis, the between-group difference in frailty was 14.7% at 12 months (95% confidence interval: 2.4%, 27.0%; P = 0.02). The score on the Short Physical Performance Battery, in which higher scores indicate better physical status, was stable in the intervention group and had declined in the control group; with the mean difference between groups being 1.44 (95% confidence interval, 0.80, 2.07; P <0.001) at 12 months. There were no major differences between the groups with respect to secondary outcomes. The few adverse events that occurred were exercise-associated musculoskeletal symptoms.
Conclusions
Frailty and mobility disability can be successfully treated using an interdisciplinary multifaceted treatment program.
Trial registration
Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12608000250336
doi:10.1186/1741-7015-11-65
PMCID: PMC3751685  PMID: 23497404
activities of daily living; frail elderly; randomized controlled trial; therapeutics; walking
15.  Effectiveness of a multifactorial intervention on preventing development of frailty in pre-frail older people: study protocol for a randomised controlled trial 
BMJ Open  2015;5(2):e007091.
Introduction
Frailty is a major concern due to its costly and widespread consequences, yet evidence of effective interventions to delay or reduce frailty is lacking. Our previous study found that a multifactorial intervention was feasible and effective in reducing frailty in older people who were already frail. Identifying and treating people in the pre-frail state may be an effective means to prevent or delay frailty. This study describes a randomised controlled trial that aims to evaluate the effectiveness of a multifactorial intervention on development of frailty in older people who are pre-frail.
Methods and analysis
A single centre randomised controlled trial with concealed allocation, assessor blinding and intention-to-treat analysis. Two hundred and thirty people aged above 70 who meet the Cardiovascular Health Study frailty criteria for pre-frailty, reside in the community and are without severe cognitive impairment will be recruited. Participants will be randomised to receive a multifactorial intervention or usual care. The intervention group will receive a 12-month interdisciplinary intervention targeting identified characteristics of frailty and problems identified during geriatric assessment. Participants will be followed for a 12-month period. Primary outcome measures will be degree of frailty measured by the number of Cardiovascular Health Study frailty criteria present, and mobility measured with the Short Physical Performance Battery. Secondary outcomes will include measures of mobility, mood and use of health and community services.
Ethics and dissemination
The study was approved by the Northern Sydney Local Health District Health Research Ethics Committee (1207-213M). The findings will be disseminated through scientific and professional conferences, and in peer-reviewed journals.
Trial registration number
Australian New Zealand Clinical Trials Registry: ACTRN12613000043730.
doi:10.1136/bmjopen-2014-007091
PMCID: PMC4322196  PMID: 25667151
GERIATRIC MEDICINE; frail elderly; randomised trial
16.  A Mobile and Ubiquitous Approach for Supporting Frailty Assessment in Elderly People 
Background
Frailty is a health condition related to aging and dependence. A reduction in or delay of the frailty state can improve the quality of life of the elderly. However, providing frailty assessments can be difficult because many factors must be taken into account. Usually, measurement of these factors is performed in a noncentralized manner. Additionally, the lack of quantitative methods for analysis makes it impossible for the diagnosis to be as complete or as objective as it should be.
Objective
To develop a centralized mobile system to conduct elderly frailty assessments in an accurate and objective way using mobile phone capabilities.
Methods
The diagnosis of frailty includes two fundamental aspects: the analysis of gait activity as the main predictor of functional disorders, and the study of a set of frailty risk factors from patient records. Thus, our system has several stages including gathering information about gait using accelerometer-enabled mobile devices, collecting values of frailty factors, performing analysis through similarity comparisons with previous data, and displaying the results for frailty on the mobile devices in a formalized way.
Results
We developed a general mechanism to assess the frailty state of a group of elders by using mobile devices as supporting tools. In collaboration with geriatricians, two studies were carried out on a group of 20 elderly patients (10 men and 10 women), previously selected from a nursing home. Frailty risk factors for each patient were collected at three different times over the period of a year. In the first study, data from the group of patients were used to determine the frailty state of a new incoming patient. The results were valuable for determining the degree of frailty of a specific patient in relation to other patients in an elderly population. The most representative similarity degrees were between 73.4% and 71.6% considering 61 frailty factors from 64 patient instances. Additionally, from the provided results, a physician could group the elders by their degree of similarity influencing their care and treatment. In the second study, the same mobile tool was used to analyze the frailty syndrome from a nutritional viewpoint on 10 patients of the initial group during 1 year. Data were acquired at three different times, corresponding to three assessments: initial, spontaneous, and after protein supplementation. The subsequent analysis revealed a general deterioration of the subset of elders from the initial assessment to the spontaneous assessment and also an improvement of biochemical and anthropometric parameters in men and women from the spontaneous assessment to the assessment after the administration of a protein supplement.
Conclusions
The problem of creating a general frailty index is still unsolved. However, in recent years, there has been an increase in the amount of research on this subject. Our studies took advantage of mobile device features (accelerometer sensors, wireless communication capabilities, and processing capacities among others) to develop a new method that achieves an objective assessment of frailty based on similarity results for an elderly population, providing an essential support for physicians.
doi:10.2196/jmir.2529
PMCID: PMC3785993  PMID: 24004497
frailty; mobile computing; similarity; elderly people
17.  Multidimensional structure of the Groningen Frailty Indicator in community-dwelling older people 
BMC Geriatrics  2013;13:86.
Background
Due to the rapidly increasing number of older people worldwide, the prevalence of frailty among older adults is expected to escalate in coming decades. It is crucial to recognize early onset symptoms to initiate specific preventive care. Therefore, early detection of frailty with appropriate screening instruments is needed. The aim of this study was to evaluate the underlying dimensionality of the Groningen Frailty Indicator (GFI), a widely used self-report screening instrument for identifying frail older adults. In addition, criterion validity of GFI subscales was examined and composition of GFI scores was evaluated.
Methods
A cross-sectional study design was used to evaluate the structural validity, internal consistency and criterion validity of the GFI questionnaire in older adults aged 65 years and older. All subjects completed the GFI questionnaire (n = 1508). To assess criterion validity, a smaller sample of 119 older adults completed additional questionnaires: De Jong Gierveld Loneliness Scale, Hospital Anxiety Depression Scale, RAND-36 physical functioning, and perceived general health item of the EuroQol-5D. Exploratory factor analysis and Mokken scale analysis were used to evaluate the structural validity of the GFI. A Venn diagram was constructed to show the composition of GFI subscale scores for frail subjects.
Results
The factor structure of the GFI supported a three-dimensional structure of the scale. The subscales Daily Activities and Psychosocial Functioning showed good internal consistency, scalability, and criterion validity (Daily Activities: Cronbach’s α = 0.81, Hs = .84, r = −.62; Psychosocial Functioning: Cronbach’s α = 0.80, Hs = .35, r = −.48). The subscale Health Problems showed less strong internal consistency but acceptable scalability and criterion validity (Cronbach’s α = .57, Hs = .35, r = −.48). The present data suggest that 90% of the frail older adults experience problems in the Psychosocial Functioning domain.
Conclusions
The present findings support a three-dimensional factor structure of the GFI, suggesting that a multidimensional assessment of frailty with the GFI is possible. These GFI subscale scores produce a richer assessment of frailty than with a single overall sum GFI score, and likely their use will contribute to more directed and customized care for older adults.
doi:10.1186/1471-2318-13-86
PMCID: PMC3766248  PMID: 23968433
Frailty; Older adults; Screening; Measurement
18.  The Hatoyama Cohort Study: Design and Profile of Participants at Baseline 
Journal of Epidemiology  2012;22(6):551-558.
Background
Investigation of frailty among elderly adults and development of prevention strategies to address this are critical in delaying progression of functional decline and thus extending healthy life expectancy. However, there has been no Japanese epidemiologic cohort study of frailty. The Hatoyama Cohort Study was launched in 2010 to identify factors that predict functional decline and to establish strategies to prevent frailty among community-dwelling elderly Japanese. This report describes the study design and the profile of the participants at baseline.
Methods
The Hatoyama Cohort Study is a prospective study of community-dwelling individuals aged 65 years or older living in the town of Hatoyama in Saitama Prefecture, Japan. Comprehensive information, including socioeconomic status, physiological indicators, physical, psychological, and cognitive function, social capital, neighborhood environment, and frailty, was collected in a baseline survey using face-to-face interviews in September 2010. Survival time, long-term care insurance certification, and medical and long-term care costs after the baseline survey will be followed. In addition, a follow-up survey will be conducted in the same manner as the baseline survey every 2 years.
Results
A total of 742 people participated in the baseline survey (mean age: 71.9 ± 5.2 years, men: 57.7%, living alone: 7.7%). Almost all participants were independent in their daily lives, and approximately 10% were categorized as frail on the kaigo-yobo (care prevention) checklist.
Conclusions
The Hatoyama Cohort Study is expected to contribute to the development of strategies that prevent frailty in later life and extend healthy life expectancy in Japan’s rapidly aging society.
doi:10.2188/jea.JE20120015
PMCID: PMC3798568  PMID: 23117221
cohort profile; community-dwelling elderly; frailty; functional decline; Hatoyama Cohort Study
19.  A comparison of Dutch frail older adults in 1998 and 2008: prevalences and determinants 
Background
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?
Objectives
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.
Methods
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.
Results
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.
Conclusions
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
20.  Frailty prevalence and slow walking speed in persons age 65 and older: implications for primary care 
BMC Family Practice  2013;14:86.
Background
Frailty in the elderly increases their vulnerability and leads to a greater risk of adverse events. According to various studies, the prevalence of the frailty syndrome in persons age 65 and over ranges between 3% and 37%, depending on age and sex. Walking speed in itself is considered a simple indicator of health status and of survival in older persons. Detecting frailty in primary care consultations can help improve care of the elderly, and walking speed may be an indicator that could facilitate the early diagnosis of frailty in primary care. The objective of this work was to estimate frailty-syndrome prevalence and walking speed in an urban population aged 65 years and over, and to analyze the relationship between the two indicators from the perspective of early diagnosis of frailty in the primary care setting.
Methods
Population cohort of persons age 65 and over from two urban neighborhoods in northern Madrid (Spain). Cross-sectional analysis. Bivariate and multivariate analysis with binary logistic regression to study the variables associated with frailty. Different cut-off points between 0.4 and 1.4 m/s were used to study walking speed in this population. The relationship between frailty and walking speed was analyzed using likelihood ratios.
Results
The study sample comprised 1,327 individuals age 65 and older with mean age 75.41 ± 7.41 years; 53.4% were women. Estimated frailty in the study population was 10.5% [95% CI: 8.9-12.3]. Frailty increased with age (OR = 1.14; 95% CI: 1.10-1.19) and was associated with poor self-rated health (OR = 2.52; 95% CI: 1.43-4.44), number of drugs prescribed (OR = 1.17; 95% CI: 1.08-1.26) and disability (OR = 6.58; 95% CI: 3.92-11.05). Walking speed less than 0.8 m/s was found in 42.6% of cases and in 56.4% of persons age 75 and over. Walking speed greater than 0.9 m/s ruled out frailty in the study sample. Persons age 75 and older with walking speed <0.8 m/s are at particularly high risk of frailty (32.1%).
Conclusions
Frailty-syndrome prevalence is high in persons aged 75 and over. Detection of walking speed <0.8 m/s is a simple approach to the diagnosis of frailty in the primary care setting.
doi:10.1186/1471-2296-14-86
PMCID: PMC3691628  PMID: 23782891
Frailty in elderly; Walking speed; Early diagnosis; Primary care
21.  Predicting ADL disability in community-dwelling elderly people using physical frailty indicators: a systematic review 
BMC Geriatrics  2011;11:33.
Background
Disability in Activities of Daily Living (ADL) is an adverse outcome of frailty that places a burden on frail elderly people, care providers and the care system. Knowing which physical frailty indicators predict ADL disability is useful in identifying elderly people who might benefit from an intervention that prevents disability or increases functioning in daily life. The objective of this study was to systematically review the literature on the predictive value of physical frailty indicators on ADL disability in community-dwelling elderly people.
Methods
A systematic search was performed in 3 databases (PubMed, CINAHL, EMBASE) from January 1975 until April 2010. Prospective, longitudinal studies that assessed the predictive value of individual physical frailty indicators on ADL disability in community-dwelling elderly people aged 65 years and older were eligible for inclusion. Articles were reviewed by two independent reviewers who also assessed the quality of the included studies.
Results
After initial screening of 3081 titles, 360 abstracts were scrutinized, leaving 64 full text articles for final review. Eventually, 28 studies were included in the review. The methodological quality of these studies was rated by both reviewers on a scale from 0 to 27. All included studies were of high quality with a mean quality score of 22.5 (SD 1.6). Findings indicated that individual physical frailty indicators, such as weight loss, gait speed, grip strength, physical activity, balance, and lower extremity function are predictors of future ADL disability in community-dwelling elderly people.
Conclusions
This review shows that physical frailty indicators can predict ADL disability in community-dwelling elderly people. Slow gait speed and low physical activity/exercise seem to be the most powerful predictors followed by weight loss, lower extremity function, balance, muscle strength, and other indicators. These findings should be interpreted with caution because the data of the different studies could not be pooled due to large variations in operationalization of the indicators and ADL disability across the included studies. Nevertheless, our study suggests that monitoring physical frailty indicators in community-dwelling elderly people might be useful to identify elderly people who could benefit from disability prevention programs.
doi:10.1186/1471-2318-11-33
PMCID: PMC3142492  PMID: 21722355
22.  Nonlinear Multisystem Physiological Dysregulation Associated With Frailty in Older Women: Implications for Etiology and Treatment 
Background
Frailty in older adults, defined as a constellation of signs and symptoms, is associated with abnormal levels in individual physiological systems. We tested the hypothesis that it is the critical mass of physiological systems abnormal that is associated with frailty, over and above the status of each individual system, and that the relationship is nonlinear.
Methods
Using data on women aged 70–79 years from the Women’s Health and Aging Studies I and II, multiple analytic approaches assessed the cross-sectional association of frailty with eight physiological measures.
Results
Abnormality in each system (anemia, inflammation, insulin-like growth factor-1, dehydroepiandrosterone-sulfate, hemoglobin A1c, micronutrients, adiposity, and fine motor speed) was significantly associated with frailty status. However, adjusting for the level of each system measure, the mean number of systems impaired significantly and nonlinearly predicted frailty. Those with three or more systems impaired were most likely to be frail, with odds of frailty increasing with number of systems at abnormal level, from odds ratios (ORs) of 4.8 to 11 to 26 for those with one to two, three to four, and five or more systems abnormal (p < .05 for all). Finally, two subgroups were identified, one with isolated or no systems abnormal and a second (in 30%) with multiple systems abnormal. The latter group was independently associated with being frail (OR = 2.6, p < .05), adjusting for confounders and chronic diseases and then controlling for individual systems.
Conclusions
Overall, these findings indicate that the likelihood of frailty increases nonlinearly in relationship to the number of physiological systems abnormal, and the number of abnormal systems is more predictive than the individual abnormal system. These findings support theories that aggregate loss of complexity, with aging, in physiological systems is an important cause of frailty. Implications are that a threshold loss of complexity, as indicated by number of systems abnormal, may undermine homeostatic adaptive capacity, leading to the development of frailty and its associated risk for subsequent adverse outcomes. It further suggests that replacement of any one deficient system may not be sufficient to prevent or ameliorate frailty.
doi:10.1093/gerona/glp076
PMCID: PMC2737590  PMID: 19567825
Frailty etiology; Aging
23.  Psychosocial factors modify the association of frailty with adverse outcomes: a prospective study of hospitalised older people 
BMC Geriatrics  2014;14(1):108.
Background
Frailty increases the risk of adverse outcomes in older people. The impact of psychosocial factors on frailty and adverse clinical outcomes associated with frailty has not yet been examined in the hospital setting. The aims of this study were to: i) investigate the association between psychosocial factors and frailty, and ii) to establish whether psychosocial factors impact on the association between frailty and adverse outcomes.
Methods
Data was collected from a Geriatric Evaluation and Management Unit (GEMU) in Australia. Frailty was identified using Fried’s frailty criteria. Psychosocial factors included wellbeing, sense of control (mastery), social activities, home/neighbourhood satisfaction, social relationships, anxiety and depression. Outcome measures were: mortality at 12 months, long length of GEMU stay (LOS), 1-month emergency rehospitalisation, and a higher level of care needed on discharge. Covariates adjusted for were age, gender and comorbidity.
Results
The mean (SD) age of participants (n = 172) at admission was 85.2 (6.4) years, with 129 (75%) female patients. 96 (56%) patients were classified as frail, with 64 (37%) pre-frail and 12 (7%) robust. Frail patients had an increased likelihood of 12-month mortality (HR, 95% CI = 3.16, 1.36–7.33), discharge to a higher level of care (OR, 95% CI = 2.40, 1.21–4.78), long LOS (OR, 95% CI = 2.04, 1.07–3.88) and 1-month emergency rehospitalisation (OR, 95% CI = 2.53, 1.10–5.82). Psychosocial factors associated with frailty included poor wellbeing, anxiety, depression, and a low sense of control. Several psychosocial factors increased the likelihood of adverse outcomes associated with frailty, including anxiety and low ratings for: wellbeing, sense of control, social activities and home/neighbourhood satisfaction.
Conclusions
Our results indicate that frail older adults with low psychosocial resources had an elevated risk of mortality, discharge to higher level care, long LOS and rehospitalisation. Consideration of psychosocial factors in comprehensive geriatric assessments will assist in patient care planning.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2318-14-108) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2318-14-108
PMCID: PMC4190287  PMID: 25262425
Frail elderly; Psychosocial factors; Geriatric assessment/methods; Hospitalisation
24.  IL-6-independent association of elevated serum neopterin levels with prevalent frailty in community-dwelling older adults 
Age and Ageing  2011;40(4):475-481.
Background: neopterin is a monocyte/macrophage-derived immune activation marker and its levels increase with age. Frailty is an important clinical syndrome of old age. Previous studies have shown significant association between elevated interleukin-6 (IL-6) levels and frailty. The objective of this study was to evaluate IL-6-independent association of serum neopterin levels with prevalent frailty.
Methods: this is a cross-sectional study in community-dwelling older adults recruited from residential and retirement communities in Baltimore, MD, USA. Frailty was determined using validated screening criteria. Serum neopterin and IL-6 levels were measured using standard enzyme-linked immunosorbent assay. Pearson correlation and multivariate linear regression analysis was performed to assess the relationship between log(neopterin) and log(IL-6). Odds ratios (ORs) for frailty were calculated using log(neopterin) and log(IL-6) as continuous measures and across tertiles of neopterin and IL-6 levels, adjusting for age, race, sex, education and body mass index.
Results: one hundred and thirty-three individuals with a mean age of 84 years (range 72–97) completed the study. Neopterin levels were significantly higher in frail older adults than those in non-frail controls [median: 8.94 versus 8.35 nM, respectively, P < 0.001 t-test on log(neopterin)]. Log(neopterin) was significantly associated with prevalent frailty, adjusting for log(IL-6). Participants in the top tertile of neopterin had OR of 3.80 [95% confidence interval (CI) = 1.36–10.6, P < 0.01] for frailty. As expected, participants in the top tertile of IL-6 had OR of 3.29 (95% CI = 1.21–7.86, P < 0.05) for frailty. Log(neopterin) correlated with log(IL-6) (correlation coefficient = 0.19, P < 0.05). Moreover, OR for participants in the top neopterin tertile remained significant after adjusting for IL-6 (OR = 3.97, 95% CI = 1.15–13.72, P < 0.05).
Conclusion: elevated neopterin levels had IL-6-independent association with prevalent frailty, suggesting potential monocyte/macrophage-mediated immune activation in the frail elderly.
doi:10.1093/ageing/afr047
PMCID: PMC3114624  PMID: 21586579
frailty; neopterin; monocyte/macrophage-mediated immune activation; IL-6; elderly
25.  Frailty and cardiovascular risk in community-dwelling elderly: a population-based study 
Background
Evidence suggests a possible bidirectional connection between cardiovascular disease (CVD) and the frailty syndrome in older people.
Purpose
To verify the relationship between CVD risk factors and the frailty syndrome in community-dwelling elderly.
Methods
This population-based study used data from the Fragilidade em Idosos Brasileiros (FIBRA) Network Study, a cross-sectional study designed to investigate frailty profiles among Brazilian older adults. Frailty status was defined as the presence of three or more out of five of the following criteria: unintentional weight loss, weakness, self-reported fatigue, slow walking speed, and low physical activity level. The ascertained CVD risk factors were self-reported and/or directly measured hypertension, diabetes mellitus, obesity, waist circumference measurement, and smoking.
Results
Of the 761 participants, 9.7% were characterized as frail, 48.0% as pre-frail, and 42.3% as non-frail. The most prevalent CVD risk factor was hypertension (84.4%) and the lowest one was smoking (10.4%). It was observed that among those participants with four or five risk factors there was a higher proportion of frail and pre-frail compared with non-frail (Fisher’s exact test: P=0.005; P=0.021). Self-reported diabetes mellitus was more prevalent among frail and pre-frail participants when compared with non-frail participants (Fisher’s exact test: P≤0.001; P≤0.001). There was little agreement between self-reported hypertension and hypertension identified by blood pressure measurement.
Conclusion
Hypertension was highly prevalent among the total sample. In addition, frail and pre-frail older people corresponded to a substantial proportion of those with more CVD risk factors, especially diabetes mellitus, highlighting the need for preventive strategies in order to avoid the co-occurrence of CVD and frailty.
doi:10.2147/CIA.S68642
PMCID: PMC4199970  PMID: 25336932
frailty syndrome; cardiovascular disease; hypertension; aged

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