Deficit Accumulation Frailty Index Research Articles

Mobility Device Use and Frailty Progression in Community-Dwelling Older Adults With Mobility Limitations.

Objective: Examine the association between mobility device use and changes in a frailty index (FI) over one year in community-dwelling older adults with mobility limitations. Methods: Analyses utilized 2015-2016 data from the National Health and Aging Trends Study community-dwelling older adults (n = 3934). We calculated a validated 40-item deficit accumulation frailty index (FI) in 2015 and 2016 and compared one year change in FI in older adults with/without canes or walkers using multivariable logistic regression. Analyses were repeated with stratification by baseline frailty. Results: Device use was not associated with worsening frailty in the overall cohort, but was associated with worsening frailty in non-frail individuals when stratified by baseline frailty. Discussion: Device use does not worsen frailty in individuals who are frail at baseline. Device users who were not frail at baseline experienced worsening frailty suggesting additional contributing factors to their frailty aside from mobility limitations.

Association between the frailty index and readmission risk in hospitalised elderly Chinese patients: a retrospective cohort study

ObjectivesFrailty is a common and important concern of the ageing population. This study examined the association between the frailty index and negative outcomes of hospitalised elderly Chinese patients.DesignRetrospective cohort study.SettingGeriatrics...

ASSOCIATIONS THAT FITNESS AND BODY MASS INDEX HAVE WITH DEFICIT ACCUMULATION FRAILTY

Abstract Lower cardiorespiratory fitness and obesity may accelerate aging processes. The degree to which changes in fitness and body mass index (BMI) may alter the rate of aging may be important for promoting lifestyle changes. We assessed cross-sectional and longitudinal associations that cardiorespiratory fitness and BMI had with a deficit accumulation frailty index (FI). Fitness (based on standardized graded exercise tests) and weight (to calculate BMI) were collected at baseline and year 4 from 3,944 participants, ages 45-76 years, in the Action for Health in Diabetes (Look AHEAD) randomized controlled clinical trial. A validated 38-item FI was used as a marker of aging. Associations between baseline levels and changes in fitness and BMI with changes in FI were assessed using linear models. Both baseline and 4-year changes in fitness and BMI were independently associated with 4-year changes in frailty (all p< 0.001). Participants with the greatest fitness increase and BMI loss tended to have improvements (i.e., decreases) in FI: mean [95% confidence interval] changes -0.019 [-0.024,-0.013]. Those with the greatest fitness loss and increases in BMI tended to have worsening (increased) FI: 0.029 [0.024,0.034]. Associations of 4-year changes in fitness and BMI with FI changes were similar across subgroups based on age, gender, baseline BMI, diabetes duration, and cardiovascular disease history. Increased fitness across 4 years was associated with less FI accumulation independent of baseline fitness. Adults with type 2 diabetes and overweight or obesity may slow aging processes by increasing their cardiorespiratory fitness and losing weight.

FRAILTY AND DEVELOPMENT ACROSS INDIAN STATES

Abstract Introduction Frailty, a common syndrome of vulnerability among older adults, provides insight into the overall health of aging populations. Life-course influences play an important role in late-life health, but the role of social and economic development has not been well-explored. We study these indicators at the state level in the Longitudinal Aging Study in India (LASI). Methods: Participants in LASI were adults aged 45 years or older from 2017-19 in 35 of 36 states and union territories. Frailty was assessed by a 48-item deficit accumulation frailty index (FI). Robust was defined as FI of 0 to 0.1, pre-frail was >0.1 – 0.2, mildly frail >0.2 – 0.3, moderately frail >0.3 – 0.4, and severely frail was >0.4. Development indicators were GDP per capita, infant mortality rate (IMR), and literacy rate in 1981 and 2018 (2011 for literacy), from the Reserve Bank of India. Associations were assessed using beta regression. Results IMR in 1981 had a small but significant association with frailty (OR 1.00 [1.00-1.00]). For GDP per capita and literacy, 1981 values were associated with greater frailty (1.15 [1.10-1.21] and 1.01 [1.01-1.01] respectively). However, 2018/2011 values were associated with lower frailty (0.94 [0.93-0.95] and 0.99 [0.99-1.00]). These associations were similar after stratifying by age group. Discussion Associations between frailty and state-level development varied both by indicator and by time of assessment. Sensitivity to the environment these indicators measure – such as IMR – may differ by age. Whether that sensitivity leads to protection or vulnerability may also change with age.

ASSOCIATION BETWEEN MULTIPLE FRAILTY INDICES AND CVD MORTALITY

Abstract Introduction Frailty, a syndrome of physiologic vulnerability, increases cardiovascular disease (CVD) risk. Which frailty tool is ideal for risk stratification remains unclear. We calculated three frailty scores from the Million Veteran Program (MVP) and examined their association with mortality and CVD in older Veterans. Methods Participants were from MVP - a large, contemporary Veteran cohort study - and aged ≥50 years at baseline (2011-2018). The frailty scores used were: MVP-FI (36-item questionnaire deficit accumulation frailty index), VA-FI (31-item EHR index), and modified Study of Osteoporotic Fractures (mSOF; a physical frailty score). MVP-FI and VA-FI scores of ≤0.10 were robust, 0.11-0.20 pre-frail, and ≥0.21 frail; mSOF scores of 0 were robust, 1 pre-frail and ≥2 frail. Primary outcomes were all-cause and CVD mortality. Secondary outcomes were incident stroke, myocardial infarction (MI), and heart failure (HF). Cox regression was used to evaluate the association of frailty with outcomes. Results Among 190,688 participants, mean age was 69 ±9, 94% were male. By MVP-FI, 29% were robust, 42% pre-frail, and 29% frail. Hazard ratios (HR, 95% CI) for all-cause mortality were 1.66 (1.61-1.72) and 3.05 (2.95-3.16) for pre-frailty and frailty, respectively. For CVD mortality, HRs were 1.76 (1.65-1.88) and 3.65 (3.43-3.90) for pre-frailty and frailty. Hazards of stroke, MI, and HF also increased with greater frailty. VA-FI and mSOF yielded concordant results. Conclusion Irrespective of measure, frailty is associated with increased all-cause mortality and CVD event risk. Clinicians and researchers may consider the most convenient tool for available data to incorporate frailty into practice.

Cumulative Deficits Frailty Index and Relationship Status Predict Survival in Patients with Multiple Myeloma

Background: Frailty is a state of decreased reserve affecting multiple organ systems, thereby increasing vulnerability to stressors. Several tools have been proposed to measure frailty in multiple myeloma (MM), such as the IMWG frailty index, and the Revised Myeloma Comorbidity Index. However, these are based on clinical trial datasets, and include chronological age as one of the indicators of frailty. A frailty index based on the principle of accumulation of health deficits (Rockwood doi:10.1093/gerona/62.7.738), provides a measure of physiologic age. This index can be readily calculated using various combinations of health deficits and has been shown to predict outcomes in several populations. Social support has been associated with improved outcomes in various populations, however its impact on survival in patients with MM has not been well studied. The objective of this study was to assess the impact of frailty measured by a deficit accumulation frailty index and the impact of relationship status on outcomes in patients with newly diagnosed MM. Methods: This is a retrospective study including patients diagnosed with MM between January 6 th, 2005, and September 19 th, 2018. We calculated a deficit accumulation frailty index using previously published methods (McNallan et. al doi.org/10.1016/j.ahj.2013.07.008, Searle et al. doi.org/10.1186/1471-2318-8-24). We used the electronic medical record system at Mayo Clinic in Rochester, MN, to extract data on activities of daily living (14 items) provided by patient-completed questionnaires, and data on comorbidities as recorded by treating providers (16 items), within 6 months prior to diagnosis. Each item was scored as 0, 0.5, or 1, with 1 indicating the presence of deficit (Table 1). The frailty index was defined as the sum of individual scores divided that by the total number of non-missing items. Patients who had N >2 missing items were excluded. Patients with a frailty index ≥0.15 were considered frail. We also extracted data on self-reported relationship status within 6 months prior to diagnosis. Variables were compared between groups using Fisher's exact test and Wilcoxon signed-rank test for categorical and continuous variables, respectively. Univariate and multivariate analysis were performed using Cox proportional hazard models. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between groups using the Log-rank test. P values <0.05 were considered statistically significant. Results: We included 578 patients. Median age was 67 (interquartile range: 59-74) years, and 40% were female. Among all patients, 226 (39%) were frail. Compared to fit patients, patients who were frail were older (median age: 70 vs. 65 years, P<0.001) and more likely to have International Staging System (ISS) III (vs. I/II) disease (47% vs. 27%, P<0.001) and ECOG performance status ≥2 (vs. 0 or 1) (45% vs. 17%, P<0.001). There was no difference in R-ISS III disease or presence of high-risk cytogenetic abnormalities between fit and frail patients. Median OS was 7.6 and 4.1 years in fit and frail patient, respectively (P<0.001). Physician assessed ECOG performance status was available for 268 patients. Among patients with ECOG performance status 0 or 1 (193 patients), 136 (70%) were fit, and 57 (30%) were frail. The OS was 8.3 and 4.6 years in the 2 groups, respectively (P=0.006) (table 2). On multivariate analysis including age, frailty status, and R-ISS stage (III vs. I/II), all were associated with OS with frailty's hazard ratio (HR): 1.4 (95%CI [1.1-1.8]), P=0.004; the HR was 1.4 (95%CI [1.1-1.9]), P=0.02, when analysis was restricted to patients ≥60 years. Among all patients, those who were married or in a committed relationship (474 patients) had improved survival (median OS: 7.0 vs. 3.7 years, respectively, P<0.001) compared to patients who were divorced/separated, widowed, or single (96 patients). On multivariate analysis, which included age, R-ISS III, frailty status, and relationship status, all were associated with OS. The HR for relationship status was 1.4 (95%CI [1.0-1.8]), P=0.0465. Conclusion: Frailty, defined by the deficit accumulation frailty index, is independently associated with decreased survival in patients with newly diagnosed MM. Being married or in a committed relationship is associated with improved survival independent of age, disease stage, and frailty.

Associations that Cardiorespiratory Fitness and Body Mass Index Loss Have with Deficit Accumulation Frailty.

Lower cardiorespiratory fitness and obesity may accelerate aging processes. The degree to which changes in fitness and body mass index (BMI) may alter the rate of aging may be important for planning treatment. We assessed cross-sectional and longitudinal associations that cardiorespiratory fitness and BMI had with a deficit accumulation frailty index (FI). Fitness, based on standardized graded exercise tests, and weight to calculate BMI at baseline and year 4 were collected from 3944 participants aged 45-76 yr in the Action for Health in Diabetes (Look AHEAD) randomized controlled clinical trial. A validated 38-item deficit accumulation FI was used as a marker of aging. Associations between baseline and changes in fitness and BMI with changes in FI were assessed using linear models. Both baseline and 4-yr changes in fitness and BMI were independently associated with 4-yr changes in frailty (all P < 0.001). Mean (95% confidence interval) changes in FI ranged from -0.019 (-0.024, -0.013) for participants in the group with the greatest fitness increase and BMI loss to 0.029 (0.024, 0.034) for participants in the group with the greatest fitness loss and BMI gain. Associations of 4-yr changes in fitness and BMI with FI changes were similar across subgroups based on age, sex, baseline BMI, diabetes duration, and cardiovascular disease history. Increased fitness across 4 yr was associated with less FI accumulation independent of baseline fitness. Adults with type 2 diabetes and overweight or obesity may slow aging processes captured by an FI by increasing their cardiorespiratory fitness and losing weight.

Association and Prognostic Value of Multidomain Frailty Defined by Cumulative Deficit and Phenotype Models in Patients With Heart Failure

BackgroundFrailty is associated with a poor prognosis in older patients with heart failure (HF). However, multidomain frailty assessment tools have not been established in patients with HF, and the association between the frailty phenotype and the deficit-accumulation frailty index in these patients is unclear. We aimed to understand this relationship and evaluate the prognostic value of the deficit-accumulation frailty index in older patients with HF. MethodsWe retrospectively analyzed FRAGILE-HF cohort, which consisted of prospectively registered hospitalized patients with HF aged ≥ 65 years. The frailty index was calculated using 34 health-related items. The physical, social, and cognitive domains of frailty were evaluated using a phenotypic approach. The primary endpoint was all-cause mortality. ResultsAmong 1027 patients with HF (median age, 81 years; male, 58.1%; median frailty index, 0.44), a higher frailty index was associated with a higher prevalence in all domains of cognitive, physical, and social frailty defined by the phenotype model. During the 2-year follow-up period, a higher frailty index was independently associated with all-cause death even after adjustment for Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score plus log B-type natriuretic peptide (per 0.1 increase: hazard ratio, 1.21; 95% confidence interval, 1.07-1.37; P = 0.002). The addition of the frailty index to the baseline model yielded statistically significant incremental prognostic value (net reclassification improvement, 0.165; 95% confidence interval, 0.012-0.318; P = 0.034). ConclusionsA higher frailty index was associated with a higher prevalence of all domains of frailty defined by the phenotype model and provided incremental prognostic information with pre-existing risk factors in older patients with HF.

Sex differences in biological aging and the association with clinical measures in older adults

Females live longer than males, and there are sex disparities in physical health and disease incidence. However, sex differences in biological aging have not been consistently reported and may differ depending on the measure used. This study aimed to determine the correlations between epigenetic age acceleration (AA), and other markers of biological aging, separately in males and females. We additionally explored the extent to which these AA measures differed according to socioeconomic characteristics, clinical markers, and diseases. Epigenetic clocks (HorvathAge, HannumAge, PhenoAge, GrimAge, GrimAge2, and DunedinPACE) were estimated in blood from 560 relatively healthy Australians aged ≥ 70 years (females, 50.7%) enrolled in the ASPREE study. A system-wide deficit accumulation frailty index (FI) composed of 67 health-related measures was generated. Brain age and subsequently brain-predicted age difference (brain-PAD) were estimated from neuroimaging. Females had significantly reduced AA than males, but higher FI, and there was no difference in brain-PAD. FI had the strongest correlation with DunedinPACE (range r: 0.21 to 0.24 in both sexes). Brain-PAD was not correlated with any biological aging measures. Significant correlations between AA and sociodemographic characteristics and health markers were more commonly found in females (e.g., for DunedinPACE and systolic blood pressure r = 0.2, p < 0.001) than in males. GrimAA and Grim2AA were significantly associated with obesity and depression in females, while in males, hypertension, diabetes, and chronic kidney disease were associated with these clocks, as well as DunedinPACE. Our findings highlight the importance of considering sex differences when investigating the link between biological age and clinical measures.

Association of geriatric measures and global frailty with cognitive decline after allogeneic hematopoietic cell transplantation in older adults

IntroductionAllogeneic hematopoietic cell transplantation (alloHCT) is increasingly offered to older adults, and its potential impact on cognition in this population is understudied. This work aims to evaluate the ability of cancer-specific geriatric assessments (cGA) and a global frailty index based on accumulation of deficits identified in the cGA to predict the risk of cognitive decline after alloHCT in older adults. Materials and MethodsAlloHCT recipients aged 50 years or older completed a cGA, including a cognitive evaluation by the Blessed Orientation Memory Concentration (BOMC) test, at baseline prior to alloHCT and then at 3, 6, and 12 months after transplant. Baseline frailty was assessed using a deficit accumulation frailty index (DAFI) calculated from the cGA. A multinomial logit model was used to examine the association between predictors (individual cGA measures, DAFI) and the following three outcomes: alive with stable or improved cognition, alive with cognitive decline, and deceased. In post-hoc analyses, analysis of variance was used to compare BOMC scores at baseline, 3, 6, and 12 months across frailty categories. ResultsIn total, 148 participants were included, with a median age of 62 (range 50–76). At baseline, 12% had cognitive impairment; at one year, 29% of survivors had improved BOMC scores, 33% had stable BOMC, and 37% had worse BOMC. Prior to transplant, 25% were pre-frail and 11% were frail. Individual baseline cGA measures were not associated with cognitive change at one year as assessed by BOMC. Adjusting for age, sex, and education, those who were frail at baseline were 7.4 times as likely to develop cognitive decline at one year than those who were non-frail, although this finding did not reach statistical significance (95% confidence interval [CI] 0.74–73.8, p = 0.09). The probability of being alive with stable/improved cognition at 12 months for the non-frail, pre-frail, and frail groups was 43%, 34%, and 8%, respectively. DiscussionBaseline geriatric measures and frailty were not significantly associated with cognitive change as assessed by BOMC in adults aged 50 or older after alloHCT. However, the study was underpowered to detect clinically meaningful differences, and future work to elucidate potential associations between frailty and cognitive outcomes is warranted.

Frailty Among Sexual and Gender Minority Older Adults: The All of Us Database.

Despite known disparities in health status among older sexual and gender minority adults (OSGM), the prevalence of frailty is unknown. The aim of this study was to develop and validate a deficit-accumulation frailty index (AoU-FI) for the All of Us database to describe and compare frailty between OSGM and non-OSGM participants. Developed using a standardized approach, the AoU-FI consists of 33 deficits from baseline survey responses of adults aged 50+. OSGM were self-reported as "not straight" or as having discordant gender and sex assigned at birth. Descriptive statistics characterized the AoU-FI. Regression was used to assess the association between frailty, age, and gender. Validation of the AoU-FI used Cox proportional hazard models to test the association between frailty categories (robust <0.15, 0.15 ≤ pre-frail ≤ 0.25, frail >0.25) and mortality. There were 9 110 OSGM and 67 420 non-OSGM with sufficient data to calculate AoU-FI; 41% OSGM versus 50% non-OSGM were robust, whereas 34% versus 32% were pre-frail, and 26% versus 19% were frail. Mean AoU-FI was 0.19 (95% confidence interval [CI]: 0.187, 0.191) for OSGM and 0.168 (95% CI: 0.167, 0.169) for non-OSGM. Compared to robust, odds of mortality were higher among frail OSGM (odds ratio [OR] 6.40; 95% CI: 1.84, 22.23) and non-OSGM (OR 3.96; 95% CI: 2.96, 5.29). The AoU-FI identified a higher burden of frailty, increased risk of mortality, and an attenuated impact of age on frailty among OSGM compared to non-OSGM. Future work is needed to understand how frailty affects the OSGM population.

Associations of frailty with overall survival (OS) and functional decline among older adults with non–small-cell lung cancer (NSCLC) receiving chemotherapy, immunotherapy, and/or targeted therapy.

12040 Background: Among older adults with cancer receiving chemotherapy, frailty indices can predict poor outcomes including survival and toxicity. Given the increasing use of immunotherapy and targeted therapy to treat NSCLC, we assessed the prognostic importance of frailty among older adults with NSCLC receiving systemic therapy. Methods: This multi-site prospective cohort study enrolled adults age ≥65 with advanced NSCLC starting chemotherapy, immunotherapy, and/or targeted therapy with non-curative intent. Patients completed geriatric assessments pretreatment and at 1, 2, 4, and 6 months. We constructed a 47-item deficit-accumulation frailty index including pretreatment demographic, geriatric assessment, and clinical factors using established methodology. Frailty scores ranged from 0 (no frailty deficits) to 1 (all frailty deficits present). We categorized patients as robust ( &lt; 0.2), pre-frail (0.2-0.34), or frail (≥0.35). The primary outcome was OS. Secondary outcomes included treatment-related grade ≥3 adverse events (AE), unplanned hospitalization, and functional decline in instrumental activities of daily living (IADL). We conducted a Kaplan-Meier survival analysis to estimate OS by frailty group and Cox proportional hazards models adjusting for treatment type. We used logistic regression models to evaluate the association of frailty with secondary outcomes adjusting for treatment type. Results: Among 149 patients, median age was 73 (range 65-94). During the study, 32% received targeted therapy, 29% immunotherapy, 27% chemoimmunotherapy, and 12% chemotherapy. Overall 43% of patients were robust, 38% pre-frail, and 19% frail. Frailty was associated with Asian race, lower education, Medicaid insurance, and no prior NSCLC surgery. Notably, frailty was not associated with age or treatment type. Median OS was 18.7 months overall: not reached for robust patients, 8.9 months for pre-frail, and 5.6 months for frail patients. Adjusting for treatment type, pre-frail (HR 2.11, 95% CI 1.24-3.60; p = 0.006) and frail (HR 2.86, 95% CI 1.52-5.39; p = 0.001) patients had worse OS compared to robust patients. During treatment, 29% developed a grade ≥3 AE, 31% had an unplanned hospitalization, and 41% developed IADL decline. Pre-frail/frail patients were more likely to develop IADL decline (HR 2.18, 95% CI 1.02-4.68; p = 0.04) than robust patients, but there were no differences in toxicity or hospitalization. Conclusions: Frailty is prognostic for OS among older adults with advanced NSCLC receiving systemic therapy across treatment types and predicted IADL decline. Frailty assessment before initiation of systemic therapy may help identify older adults with advanced NSCLC at higher risk of poor outcomes to inform decision making, individualize anticipatory guidance, and optimize supportive care.

The association of allopurinol with persistent physical disability and frailty in a large community based older cohort.

The protective effects of allopurinol on physical function in older adults are not well understood, despite its potential to improve functional gains and reduce sarcopenia. This study aims to determine the association between allopurinol, persistent physical disability, and frailty in older gout patients. This analysis used data from a randomized trial in an older cohort, ASPirin in Reducing Events in the Elderly (ASPREE). ASPREE recruited 19,114 participants aged ≥65 years without prior cardiovascular events, dementia, or independence-limiting physical disability at trial enrolment. This analysis examined the association of baseline and time-varying allopurinol use with persistent physical disability and new-onset frailty in participants with gout at baseline (self-report or use of any anti-gout medications). Frailty was measured using the Fried frailty phenotype (score ≥3/5) and a deficit accumulation frailty index (FI) (score >0.21/1.0). Multivariable Cox proportional-hazards models were used for main analyses. This analysis included 1155 gout participants, with 630 taking allopurinol at baseline and 525 not. During a median follow-up of 5.7 years, 113 new allopurinol users were identified. Compared with nonusers, baseline allopurinol use was associated with a significant risk reduction of persistent physical disability (Adjusted HR 0.46, 95% CI 0.23-0.92, p = 0.03). The strength of the association was modestly attenuated in the time-varying analysis (Adjusted HR 0.56, 0.29-1.08, p = 0.08). No significant associations with frailty measures were observed for either baseline allopurinol use (Fried frailty: Adjusted HR 0.83, 0.62-1.12; FI: Adjusted HR 0.96, 0.74-1.24) or time-varying allopurinol use (Fried frailty: Adjusted HR 0.92, 0.69-1.24; FI: Adjusted HR 1.02, 0.78-1.33). Allopurinol use in older adults with gout is associated with a reduced risk of persistent physical disability but not associated with risk of frailty.

Cognitive function is mediated by deficit accumulation in older, long-term breast cancer survivors.

This study aims to examine whether cognitive function in older, long-term breast cancer survivors is both a direct effect of cancer and cancer treatments and an indirect effect mediated by deficit accumulation. Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5-15-year survivors (N = 220) and age- and education-matched non-cancer controls (N = 123) were assessed at enrollment and at 8-, 16-, and 24-month follow-ups with standard neuropsychological tests and the comprehensive geriatric assessment which was used to calculate the deficit accumulation frailty index (DAFI). Blood or saliva samples for APOE genotyping were collected at enrollment. Participants were purposely recruited so that approximately 50% had a history of treatment with chemotherapy or and 50% were not exposed to chemotherapy. Latent variable mediation analysis revealed that cognitive performance was mediated by deficit accumulation for all three domains. The direct effect of cancer diagnosis and treatment history was significant for the Language domain (p = 0.04), a trend for the learning and memory domain (p = 0.054), and non-significant for the attention, processing speed, executive function (APE) domain. Carrying the APOE ε4 allele had a significant negative direct effect on the APE domain (p = 0.05) but no indirect effect through deficit accumulation. Cognitive function in older, long-term breast cancer survivors appears to be primarily mediated through deficit accumulation. These findings have important clinical implications suggesting that the most effective intervention to prevent or slow cognitive aging in older cancer survivors may be through prevention or management of comorbidities and interventions that maintain functional capacity (exercise, physical therapy) and social and mental health.

The association between frailty and incident cardiovascular disease events in community-dwelling healthy older adults

Study objectiveThis study examined the association between frailty and incident cardiovascular disease (CVD) events, major adverse cardiovascular events (MACE), and CVD-related mortality. DesignLongitudinal cohort study. SettingThe ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial in Australia and the United States. Participants19,114 community-dwelling older adults (median age 74.0 years; 56.4 % females). InterventionsPre-frailty and frailty were assessed using a modified Fried phenotype and a deficit accumulation Frailty Index (FI) at baseline. Main outcome measuresCVD was defined as a composite of CVD death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure; MACE included all except heart failure. Cox proportional hazards regression was used to analyze the association between frailty and CVD outcomes over a median follow-up of 4.7 years. ResultsBaseline pre-frail and frail groups had a higher risk of incident CVD events (Hazard Ratio (HR): 1.31; 95 % Confidence Interval (CI): 1.14–1.50 for pre-frail and HR: 1.63; 95 % CI: 1.15–2.32 for frail) and MACE (pre-frail HR: 1.26; 95 % CI: 1.08–1.47 and frail HR: 1.51; 95 % CI: 1.00–2.29) than non-frail participants according to Fried phenotype after adjusting for traditional CVD risk factors. Effect sizes were similar or larger when frailty was assessed with FI; similar results for men and women. ConclusionFrailty increases the likelihood of developing CVD, including MACE, in community-dwelling older men and women without prior CVD events. Screening for frailty using Fried or FI method could help identify community-dwelling older adults without prior CVD events who are more likely to develop CVD, including MACE, and may facilitate targeted preventive measures to reduce their risk.

The Association between Frailty and Dementia-Free and Physical Disability-Free Survival in Community-Dwelling Older Adults

Introduction: Frailty is a common geriatric syndrome that adversely impacts health outcomes. This study examined correlates of physical frailty in healthy community-dwelling older adults and studied the effect of frailty on disability-free survival (DFS), defined as survival free of independence-limiting physical disability or dementia. Methods: This is a post hoc analysis of 19,114 community-dwelling older adults (median age: 74.0 years, interquartile range or IQR: 6.1 years) from Australia and the USA enrolled in the “ASPirin in Reducing Events in the Elderly (ASPREE)” clinical trial. Frailty was assessed using a modified Fried phenotype and a deficit accumulation frailty index (FI) utilizing a ratio score derived from 66 items. Multinomial logistic regression was used to examine the correlates of frailty and Cox regression to analyze the association between frailty and DFS (and its components). Results: At study enrollment, 39.0% were prefrail, and 2.2% of participants were frail, according to Fried phenotype. Older age, higher waist circumference, lower education, ethnoracial origin, current smoking, depression, and polypharmacy were associated with prefrailty and frailty according to Fried phenotype and FI. Fried phenotype defined prefrailty and frailty predicted reduced DFS (prefrail: HR: 1.67; 95% CI: 1.50–1.86 and frail: HR: 2.80; 95% CI: 2.27–3.46), affecting each component of DFS including dementia, physical disability, and mortality. Effect sizes were larger, according to FI. Conclusion: Our study showed that prefrailty is common in community-dwelling older adults initially free of cardiovascular disease, dementia, or independence-limiting physical disability. Prefrailty and frailty significantly reduced disability-free survival. Addressing modifiable correlates, like depression and polypharmacy, might reduce the adverse impact of frailty on dementia-free and physical disability-free survival.

POLYPHARMACY, FRAILTY, AND DISABILITY-FREE SURVIVAL IN COMMUNITY-DWELLING HEALTHY OLDER INDIVIDUALS

Abstract BACKGROUND Polypharmacy and frailty are two common geriatric syndromes. We examined the association between polypharmacy and frailty and if, together, they predicted disability-free survival (DFS), defined as time to the first event of dementia, persistent physical disability or death. METHODS We included 19,114 participants from the "ASPirin in Reducing Events in the Elderly" (ASPREE) clinical trial. Polypharmacy was defined as regular, concomitant use of five or more prescription medications. Frailty was assessed using a modified Fried phenotype and a deficit accumulation frailty index (FI) of 66 items. The association between polypharmacy and frailty was assessed by multinomial logistic regression. In addition, Cox regression was used to determine the association between polypharmacy-exposed frailty and DFS. RESULTS Individuals with polypharmacy (vs. &amp;lt; 5 medications) were 55% more likely to be pre-frail (Relative Risk Ratio or RRR: 1.55; 95%Confidence Interval or CI:1.44, 1.68) and three times more likely to be frail (RRR: 3.34; 95%CI: 2.64, 4.22) according to Fried phenotype. Frail individuals had a two-fold reduction in their survival free of dementia/disability (Hazard ratio or HR: 2.16; 95%CI: 1.56, 2.99), whereas frail individuals with polypharmacy had a four-fold reduction (HR: 4.24; 95%CI: 3.28, 5.47). Effect sizes were more prominent when frailty was assessed using the FI than when assessed by Fried phenotype. CONCLUSION Polypharmacy was significantly associated with pre-frailty/frailty. Polypharmacy-exposed pre-frailty/frailty increased the risk of death, dementia or physical disability among older adults. Addressing polypharmacy in older people could ameliorate the impact of frailty on individuals’ functional status, cognition and survival.

DEVELOPING A NOVEL FRAILTY INDEX TO STUDY FRAILTY OF SEXUAL AND GENDER MINORITY OLDER ADULTS IN THE ALL OF US DATABASE

Abstract Prevalence of frailty among older sexual and gender minority adults (OSGM) is unknown despite disparities in mental health, medical comorbidities, and physical function. The NIH-funded All of Us Program was launched May 2018 aiming to enroll 1 million US participants focusing on those underrepresented in biomedical research, including OSGM. Using validated methods, we developed an All of Us deficit accumulation frailty index (AoU-FI) consisting of 33-items using baseline survey responses of adults aged 50+. Deficit domains include comorbidities, physical functioning, mental health, cognition, and sensory impairment. AoU-FI was valid if ≤20% of items were missing and ≤70% were comorbidities. OSGM self-identified or had discordance between gender and sex responses. OSGM (n=5,678) and non-OSGM (n=66,325), were similar in age (mean (IQR) = 66.7 (60–73) vs 66.9 (60–74)) but were more diverse (White 78% vs 82%, Black 7.5% vs. 6.5%, Hispanic/Latino 6.9% vs. 5.9%). AoU-FI had an expected gamma distribution across groups. OSGM frailty had a narrower range (0–0.67 vs. 0–0.75) and higher mean of 0.19 (sd=0.11) vs 0.17 (sd=0.1) compared to non-OSGM. To our knowledge, this is the first study of frailty among OSGM. Findings suggest OSGM experience worse frailty, highlighting the need to understand disparities in frailty, identify interventions, and develop policies to support OSGM. Additionally, our novel AoU-FI creates opportunities to apply frailty to diverse participants and types of data from digital health to genomics within the All of Us database.

FRAILTY AND CARDIOVASCULAR DISEASE EVENTS IN COMMUNITY-DWELLING HEALTHY OLDER ADULTS

Abstract BACKGROUND Frailty is associated with adverse outcomes, but whether it independently increases cardiovascular disease (CVD) risk requires clarification. METHODS This study examined the association between frailty in a cohort with no previous CVD events and subsequent CVD outcomes in 19,114 community-dwelling older people from the ASPREE trial. Frailty was assessed using the modified Fried phenotype, comprising weakness, exhaustion, low body mass index (BMI), slowness and low physical activity, and a deficit accumulation frailty index (FI) of 66 items. CVD event was defined as a composite of CVD death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for heart failure. Results Over a median 4.7-years of follow-up (interquartile range: 3.6 to 5.7 years), pre-frail/frail participants were more likely to develop CVD events (Hazard ratio (HR): 1.33; 95% Confidence Interval (CI): 1.16, 1.53 for pre-frail and HR: 1.68; 95% CI: 1.19, 2.38 for frail participants) according to Fried phenotype. Subtypes of CVD (fatal/non-fatal myocardial infarction and heart failure hospitalization) similarly increased HRs except fatal or non-fatal stroke. These effect sizes were more prominent when frailty was assessed using the FI than that assessed by Fried phenotype. CONCLUSION Pre-frail and frail participants were at significantly increased risk of developing CVD and its sub-types (particularly fatal/non-fatal myocardial infarction and hospitalization for heart failure). Addressing pre-frailty and frailty in older people could contribute to CVD prevention strategies.

The Association between Metabolic Syndrome, Frailty and Disability-Free Survival in Healthy Community-dwelling Older Adults.

To examine the association between metabolic syndrome (MetS) and frailty, and determine whether co-existent MetS and frailty affect disability-free survival (DFS), assessed through a composite of death, dementia or physical disability. Longitudinal study. Community-dwelling older adults from Australia and the United States (n=18,264) from "ASPirin in Reducing Events in the Elderly" (ASPREE) study. MetS was defined according to American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines (2018). A modified Fried phenotype and a deficit accumulation Frailty Index (FI) were used to assess frailty. Association between MetS and frailty was examined using multinomial logistic regression. Cox regression was used to analyze the association between MetS, frailty and DFS over a median follow-up of 4.7 years. Among 18,264 participants, 49.9% met the criteria for MetS at baseline. Participants with Mets were more likely to be pre-frail [Relative Risk Ratio (RRR): 1.22; 95%Confidence Interval (CI): 1.14, 1.30)] or frail (RRR: 1.66; 95%CI: 1.32, 2.08) than those without MetS. MetS alone did not shorten DFS while pre-frailty or frailty alone did [Hazard Ratio (HR): 1.68; 95%CI: 1.45, 1.94; HR: 2.65; 95%CI:1.92, 3.66, respectively]. Co-existent MetS with pre-frailty/frailty did not change the risk of shortened DFS. MetS was associated with pre-frailty or frailty in community-dwelling older individuals. Pre-frailty or frailty increased the risk of reduced DFS but presence of MetS did not change this risk. Assessment of frailty may be more important than MetS in predicting survival free of dementia or physical disability.