Risk Of Incident Frailty Research Articles

Dietary inflammatory index, mediating biomarkers and incident frailty in Chinese community-dwelling older adults

ObjectivesDiet can modulate systemic inflammation, while inflammation is a critical contributory factor of frailty. However, longitudinal data on the association between dietary inflammatory index (DII) and frailty are limited, and the intermediate mechanisms remain unclear. This study aimed to examine the association between DII and incident frailty and the potential mediating roles of frailty-related biomarkers. DesignProspective cohort study. SettingThe Mr. OS and Ms. OS (Hong Kong) study. ParticipantsA total of 3,035 community-dwelling men and women aged above 65 years without frailty at baseline were included. MeasurementsDII scores were calculated using the locally validated food frequency questionnaire. Incident frailty at year four was defined using the Fried frailty phenotype. Logistic regression was used to examine the association between DII and frailty onset. Mediation analysis was used to explore the mediating roles of frailty-related biomarkers in the DII-frailty association. ResultsDuring four years of follow-up, 208 individuals developed frailty. Compared with the lowest tertile of DII, the highest tertile was associated with an increased risk of incident frailty (OR: 1.82; 95% CI: 1.17–2.82; p = 0.008) after adjustment for relevant confounders. The DII-frailty association was significant in men but not in women. Furthermore, increasing serum homocysteine, decreasing serum folate, and reducing estimated glomerular filtration rate (eGFR) mediated 11.6%, 7.1%, and 9.6 % of the total relation between DII and frailty onset, respectively. ConclusionIn this cohort study, a pro-inflammatory diet was associated with a higher risk of frailty onset, mediated by homocysteine, folate, and renal function.

Prediction model related to 6-year risk of frailty in older adults aged 65 years or above in China

Objective: To develop a prediction tool for 6-year incident risk of frailty among Chinese older adults aged 65 years or above. Methods: Data from the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 was used, including 13 676 older adults aged 65 years or above who were free of frailty at baseline. Key predictors of frailty were identified via the least absolute shrinkage and selection operator (LASSO) method, and were thereafter used to predict the incident frailty based on the Cox proportional hazards regression model. The model was internally validated by 2 000 Bootstrap resamples and evaluated for the performance of discrimination and calibration using the area under the receiver operating characteristic curve (AUC) and calibration curve, respectively. The net benefit of the developed prediction tool was evaluated by decision-curve analysis. Results: The M(Q1, Q3) age and follow-up time of the participants were 81.0 (71.0, 90.0) years and 6.0 (4.1, 9.2) years, respectively. A total of 4 126 older persons (30.2%) were recorded with frailty incidents during the follow-up, with the corresponding incidence density of 41.8/1 000 person-years. A total of 15 key predictors of frailty were selected by LASSO, namely, age, sex, race, education years, meat consumption, tea drinking, performing housework, raising domestic animals, playing cards or mahjong, and baseline status of visual function, activities of the daily living score, instrumental activities of the daily living score, hypertension, heart disease, and self-rated health. The prediction model was internally validated with an AUC of 0.802, with the max Youden's index of 0.467 at a risk threshold of 19.0%. The calibration curve showed high consistency between predicted probabilities and observed proportions of frailty events. The decision curve indicated that higher net benefits could be obtained via the prediction model than did strategies based on intervention in all or none participants for any risk threshold less than 59%, and the model-based net benefit was estimated to be 0.10 at a risk threshold of 19.0%. Conclusions: The herein developed 6-year incident risk prediction model of frailty, based on easily accessible questionnaires and physical examination variables, has good predictive performance. It has application potential in identifying populations at high risk of incident frailty.

Epigenetic age acceleration and the risk of frailty, and persistent activities of daily living (ADL) disability

Abstract Background Epigenetic ageing is among the most promising ageing biomarkers and may be a useful marker of physical function decline, beyond chronological age. This study investigated whether epigenetic age acceleration (AA) is associated with the change in frailty scores over 7 years and the 7-year risk of incident frailty and persistent Activities of Daily Living (ADL) disability among 560 Australians (50.7% females) aged ≥70 years. Methods Seven AA indices, including GrimAge, GrimAge2, FitAge and DunedinPACE, were estimated from baseline peripheral-blood DNA-methylation. Frailty was assessed using both the 67-item deficit-accumulation frailty index (FI) and Fried phenotype (Fried). Persistent ADL disability was defined as loss of ability to perform one or more basic ADLs for at least 6 months. Linear mixed models and Cox proportional-hazard regression models were used as appropriate. Results Accelerated GrimAge, GrimAge2, FitAge and DunedinPACE at baseline were associated with increasing FI scores per year (adjusted-Beta ranged from 0.0015 to 0.0021, P < 0.05), and accelerated GrimAge and GrimAge2 were associated with an increased risk of incident FI-defined frailty (adjusted-HRs 1.43 and 1.39, respectively, P < 0.05). The association between DunedinPACE and the change in FI scores was stronger in females (adjusted-Beta 0.0029, P 0.001 than in males (adjusted-Beta 0.0002, P 0.81). DunedinPACE, but not the other AA measures, was also associated with worsening Fried scores (adjusted-Beta 0.0175, P 0.04). No associations were observed with persistent ADL disability. Conclusion Epigenetic AA in later life is associated with increasing frailty scores per year and the risk of incident FI-defined frailty.

Circadian disturbances and frailty risk in older adults

Frailty is characterized by diminished resilience to stressor events. It is associated with adverse future health outcomes and impedes healthy aging. The circadian system orchestrates ~24-h rhythms in bodily functions in synchrony with the day-night cycle, and disturbed circadian regulation plays an important role in many age-related health consequences. We investigated prospective associations of circadian disturbances with incident frailty in over 1000 older adults who had been followed annually for up to 16 years. We found that decreased rhythm strength, reduced stability, or increased variation were associated with a higher risk of incident frailty and faster progress of frailty over time. Perturbed circadian rest-activity rhythms may be an early sign or risk factor for frailty in older adults.

Tobacco Smoking and Pack-Years Are Associated With Frailty Among People With HIV.

Tobacco smoking increases frailty risk among the general population and is common among people with HIV (PWH) who experience higher rates of frailty at younger ages than the general population. We identified 8608 PWH across 6 Centers for AIDS Research Network of Integrated Clinical Systems sites who completed ≥2 patient-reported outcome assessments, including a frailty phenotype measuring unintentional weight loss, poor mobility, fatigue, and inactivity, and scored 0-4. Smoking was measured as baseline pack-years and time-updated never, former, or current use with cigarettes/day. We used Cox models to associate smoking with risk of incident frailty (score ≥3) and deterioration (frailty score increase by ≥2 points), adjusted for demographics, antiretroviral medication, and time-updated CD4 count. The mean follow-up of PWH was 5.3 years (median: 5.0), the mean age at baseline was 45 years, 15% were female, and 52% were non-White. At baseline, 60% reported current or former smoking. Current (HR: 1.79; 95% confidence interval: 1.54 to 2.08) and former (HR: 1.31; 95% confidence interval: 1.12 to 1.53) smoking were associated with higher incident frailty risk, as were higher pack-years. Current smoking (among younger PWH) and pack-years, but not former smoking, were associated with higher risk of deterioration. Among PWH, smoking status and duration are associated with incident and worsening frailty.

Vitamin K insufficiency predicts incidence of frailty in community-dwelling older adults: The Otassha Study.

Vitamin K is a fat-soluble vitamin discovered as an essential factor for blood coagulation. It is suggested that vitamin K can benefit several aging-related diseases, including osteoporosis, osteoarthritis, and dementia. We previously reported the cross-sectional association of vitamin K insufficiency with frailty in community-dwelling older adults. In October 2020, a health examination of community-dwelling older adults (The Otassha Study) was performed, including frailty evaluation and blood tests. We used a ucOC and OC ratio (ucOC/OC) to indicate vitamin K insufficiency. One year later, we conducted a follow-up evaluation of frailty on 518 people who were not frail at baseline. The serum ucOC/OC at the baseline examination was divided into quartiles (Q1, Q2, Q3, and Q4). Odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariate binary logistic regression for each quartile of ucOC/OC to determine the risk of incident frailty in the follow-up study, with the lowest quartile (Q1) as the reference. Among the 518 older adults who were not frail at baseline, 66 people (12.7%) became frail in the follow-up study. In the multivariate binary logistic regression analysis, setting the lowest quartile of ucOC/OC (Q1) as a reference, the OR of the incident frailty in the highest quartile (Q4) was 2.53 (95% CI 1.07, 4.92) which was significantly different from Q1. The findings of this longitudinal study suggest that vitamin K insufficiency has nutritional importance in predicting the future incidence of frailty in the Japanese older adult population.

CREATION AND VALIDATION OF A POLYSOCIAL SCORE FOR PHYSICAL FRAILTY AMONG COMMUNITY-DWELLING OLDER ADULTS IN THE US

Abstract The interrelatedness between social determinants of health impedes researchers from identifying important social factors for health investment. A new approach is needed to quantify the aggregate effect of social factors and develop person-centered social interventions. Data are from the Health and Retirement Study; 6,075 older adults initially not frail (non-frail or prefrail) were included. Frailty was assessed by slowness, weakness, exhaustion, inactivity, and shrinking. Persons were classified as “nonfrail” (0 criteria), “prefrail” (1–2 criteria), or “frail” (3–5 criteria). We included 24 social factors from five categories (economic stability, neighborhood environment, education, community/social context, and healthcare system) and used forward stepwise regression to screen for important ones. Polysocial score was created using 15 social factors and was classified as low (0-29), intermediate (30-42), and high (43+). We used the Poisson regression to estimate the risk of incident frailty by three polysocial score categories. We found that 444 (34.5%), 651 (17.9%), and 108 (9.4%) cases of incident frailty at the 4-year follow-up among participants with a low, intermediate, and high polysocial score, respectively. In the multivariable-adjusted Poisson model, the risk of frailty among participants in the intermediate and high polysocial score categories was 35% and 59% lower than those in the low polysocial score category, respectively. We found a universal association between polysocial scores and frailty across race/ethnicity and sex subgroups. The polysocial approach may offer possible solutions to monitor social environments and suggestions for older people to improve their social status for specific health outcomes.

Associations of physical activity participation trajectories with subsequent motor function declines and incident frailty: A population-based cohort study

Maintaining physical function and delaying frailty are of significant importance in both quality of life and health longevity for successful aging. The objective of this study is to investigate whether different trajectories of long-term physical activity (PA) participation are associated with subsequent motor function declines and incident frailty in middle-aged and elderly adults. Data from 8,227 aged ≥ 50 years adults enrolled in the English Longitudinal Study of Aging were analyzed. Long-term PA participation trajectories were assessed using group-based trajectory modeling over the first 6-year period from wave 1 (2002-2003) to wave 4 (2008-2009). The longitudinal associations of PA trajectories with motor function declines and incident frailty were evaluated by a linear mixed model and Cox regression model, respectively, with follow-up of 10 years from wave 4 to wave 9 (2018-2019). Five distinct trajectories of long-term PA participation were identified in the aging cohort, including persistently low-active trajectory (N = 2,039), increasing active trajectory (N = 1,711), declining active trajectory (N = 216), persistently moderate-active trajectory (N = 2,254), and persistently high-active trajectory (N = 2,007). Compared with the persistently low-active group, the participants in persistently moderate- and high-active groups experienced significantly decelerated grip strength decline, decreased gait speed decline, and faster chair rises after multiple-adjustment. Similarly, participants maintaining moderate- and high-active PA were also associated with a lower risk of incident frailty (multiple-adjusted hazard ratio: 0.70, 95% confidence interval: 0.62-0.80, and 0.42, 95% CI: 0.36-0.49, respectively), compared with those with persistently low PA. Notably, the participants with the increasing active trajectory got similar health benefits as those with persistently moderate and high levels of PA. In addition to persistent PA, increasing PA was linked to a slower decline in motor function and lower risk of incident frailty in the cohort. Our findings suggest that regular PA is never too late.

Glomerular filtration rate by different measures and albuminuria are associated with risk of frailty: the Rugao Longitudinal Ageing Study.

A decreased estimated glomerular filtration rate (eGFR) is associated with frailty, but the association between kidney function and frailty using multidimensional assessments has not been entirely examined. We aimed to investigate whether albuminuria and the eGFR using different biomarkers were associated with frailty. A total of 1830 older adults were included. Kidney function was assessed by the eGFR (based on combined creatinine-cystatin C [eGFRcr-cys]) and β2-microglobulin [eGFRB2M]) and urine albumin-creatinine ratio (UACR). Frailty was measured by the Fried phenotype (FP) and frailty index (FI). Logistic regression models were used to investigate cross-sectional and longitudinal associations of baseline kidney measures with prevalent and incident frailty. At baseline, kidney function was associated with prevalent frailty. During the 2-year follow-up, a decreased eGFR (per 10 units) was associated with an increased risk of incident frailty using the FP (eGFRcr-cys: OR 1.18, 95% CI 1.03-1.35; eGFRB2M: OR 1.14, 95% CI 1.02-1.29, respectively) and FI (eGFRB2M: OR 1.18, 95% CI 1.04-1.65). An increased logUACR was associated with a higher risk of incident frailty using the FP (OR 1.18, 95% CI 1.03-1.35). Additionally, individuals with chronic kidney disease (CKD) had a higher risk of incident frailty using the FP (eGFRcr-cys: OR 2.13, 95% CI 1.28-3.47; eGFRB2M: OR 1.58, 95% CI 1.10-2.29, respectively) and FI (eGFRcr-cys: OR 1.97, 95% CI 1.15-3.32; eGFRB2M: OR 1.51, 95% CI 1.03-2.24, respectively). Kidney function decline and CKD were associated with an increased risk of prevalent and incident frailty in older adults. Physicians should pay more attention to monitoring frailty status in older adults with CKD, even in those with kidney function decline.

The frailty risk trajectory associated with kidney and cardiovascular morbidities among patients with incident diabetes: A population-based study

Background and aimsFrailty denotes the increased vulnerability to stressors/insults associated with aging or diseases, and has high incidence in patients with diabetes mellitus (DM). We hypothesized that chronic kidney disease (CKD) and non-kidney morbidities in patients with newly diagnosed DM might modulate their risk of developing incident frailty. MethodsFrom the Longitudinal Cohort of Diabetes Patients, we identified 322,109 patients with newly diagnosed DM, and classified them into those without CKD, with CKD before and after DM. We used Kaplan-Meier analyses and Cox proportional hazard regression to analyze associations between CKD or non-kidney morbidities and the risk of incident frailty. We further analyzed the year-to-year trend of frailty risk brought by CKD or non-kidney morbidities. ResultsPatients with DM but without CKD (n = 249,752; 77.5%), with CKD prior to (n = 23,829; 7.4%), and after DM (n = 48,528; 15.1%) were enrolled. Those with CKD, regardless of onset timing, had a significantly higher risk of developing frailty than those without (for onset prior to DM, hazard ratio (HR) 1.235, 95% confidence interval (CI) 1.11–1.38; for onset after DM, HR 1.386, 95% CI 1.21–1.59). The risk was more prominent early after the diagnosis of DM was made. Patients with chronic obstructive pulmonary disease, liver, and cardiovascular morbidities all had a significantly higher risk of frailty than those without, with cerebrovascular accident carrying the most prominent risk elevation (HR 4.059, 95% CI 3.73–4.42). ConclusionsCKD regardless of onset timing relative to DM predicted a higher risk of incident frailty, while non-kidney morbidities including cardiovascular morbidities, similarly increased frailty risk among incident diabetic patients.

Earlier menopause is associated with higher risk of incident frailty in community-dwelling older women in England.

Although it is well known that women have higher risk of frailty, mechanisms are not clear. Reproductive history may be related to the sex difference in frailty. A total of 1249 community-dwelling women aged ≥60 in England were examined for associations between age at menopause and risk of developing frailty. Frailty defined by the frailty phenotype was measured at baseline and 4 years later. Age at menopause was used as a continuous variable and categorical groups: premature/early (10-45 years), normal (46-55 years), and late (56 years or older). Men with comparable conditions from the same cohort were also used as a comparison. Earlier age at menopause was significantly associated with higher risk of incident frailty. One year later menopause age was associated with a 3% decrease in incident frailty risk (Odds ratio [OR]=0.97, 95%CI=0.95-1.00, p=0.02). Women with premature or early menopause had a significantly higher risk of developing frailty compared with those with normal menopause (OR=1.90, 95%CI=1.28-2.81, p=0.001), while those with late menopause did not. In a supplementary analysis with older men, older women with premature or early menopause were more likely to develop frailty compared with older men (OR=2.29, 95%CI=151-3.48, p < 0.001), however, there was no significant difference between women with normal or late menopause. Earlier menopause was significantly associated with higher risk of developing frailty. Our findings suggest that menopause or its related factors, such as decline in estrogen after menopause, potentially play an important role in the sex difference in frailty.

Adherence to the Mediterranean diet and incident frailty: Results from a longitudinal study

ObjectivesThe aim of the current prospective study was to examine the relationship between adherence to the Mediterranean diet and incident frailty. Study design1075 Greek community-dwelling older adults from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were included in the present longitudinal analysis. Main outcome measuresAdherence to the Mediterranean diet was evaluated through the MedDietScore, calculated from the information participants provided on a validated food frequency questionnaire. Frailty was assessed using two multidomain tools: the Frailty Index (FI) and the Tilburg Frailty Indicator (TFI). Analysis of the incidence of frailty as a function of the baseline MedDietScore was performed using Cox proportional hazards models. Additionally, Generalized Estimating Equations (GEE) models were used to explore whether the baseline MedDietScore was associated with the change in the total number of frailty criteria met by participants over time. In testing for a dose–response association between Mediterranean diet and frailty, the MedDietScore was treated either as a continuous variable or as tertiles of low, medium and high adherence to MeDi. Results176 and 131 participants developed incident frailty, as measured with the FI and TFI respectively. Each unit of MedDietScore was associated with a 5% (ΗR 0.95, 95% CI 0.91–0.99, p = 0.012) and 10% (ΗR 0.90, 95% CI 0.86–0.95, p ≤ 0.001) decrease in the risk of incident frailty when measured with the FI and TFI respectively. Compared with participants reporting low adherence to the Mediterranean diet (lowest tertile), those with high adherence (highest tertile) had a 41% (ΗR 0.59, 95% CI 0.38–0.91, p = 0.017) and a 57% (ΗR 0.43, 95% CI 0.27–0.70, p ≤ 0.001) lower risk of incident frailty as measured with the FI and TFI respectively. After excluding from the analyses participants diagnosed with dementia at baseline or follow-up, the same results were obtained: each unit of MedDietScore was associated with a 5% (HR 0.95 CI 0.91–0.99, p = 0.023) and a 10% (HR 0.90 CI 0.86–0.94, p ≤ 0.001) decrease in the risk of incident frailty as measured with the FI and TFI respectively. ConclusionsThe present longitudinal study showed that non-frail community-dwelling older adults with high adherence to the Mediterranean dietary pattern had a significantly lower incidence of frailty.

Association of urinary albumin:creatinine ratio with incident frailty in older populations.

ABSTRACTBackgroundThe longitudinal relationship of albuminuria with incident frailty remains unknown. Therefore we aimed to evaluate the relation of albuminuria with the risk of incident frailty in older adults.MethodsA total of 1115 participants ≥65 years of age (average age 80.3 years) who were free of frailty in the Chinese Longitudinal Healthy Longevity Survey were included. The outcome was incident frailty, defined as a frailty index ≥0.25 during follow-up. Cox proportional hazards models were used to assess the association of the urinary albumin:creatinine ratio (UACR) with frailty.ResultsDuring a median follow-up duration of 5.3 years, 295 (26.5%) participants developed incident frailty. Overall, the UACR was significantly positively associated with the risk of incident frailty (P for trend = 0.005), with a significantly higher risk of incident frailty in participants in the quartile 4 of UACR {≥13.43 mg/g; hazard ratio [HR] 1.64 [95% confidence interval (CI) 1.13–2.37]} compared with those in quartile 1 (<0.73 mg/g). Consistently, when UACRs were assessed as clinical categories, compared with participants with UACR <10 mg/g, those with UACR ≥30 mg/g had a higher HR of incident frailty [HR 1.61 (95% CI 1.17–2.20)]. Accounting for the competing risk of death also did not substantially change the results. In addition, a stronger positive association between UACR and incident frailty was found in those with a higher high-sensitivity C-reactive protein level (hs-CRP) (P for interaction = 0.045).ConclusionAlbuminuria was positively associated with the risk of incident frailty, particularly in those with higher hs-CRP, emphasizing the importance of managing both albuminuria and inflammation for primary prevention of frailty.

Association of immunity markers with the risk of incident frailty: the Rugao longitudinal aging study

BackgroundThe neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) are readily available circulatory immunity markers that are associated with components of frailty. However, few studies have investigated the relationship between these immunity markers and frailty, and it remains unknown whether they are predictive of incident frailty in older adults in general. Hence, we aimed to examine the association of these immunity markers with the risk of incident frailty.ResultsOverall, 1822 older adults (mean age was 78.03 ± 4.46 years) were included in the Rugao Longitudinal Aging Study. NLR, PLR and SII were calculated from blood cell counts. The frailty definition was based on the Fried phenotype. At baseline, 200 (10.98%) individuals were defined as frailty, and no significant associations of NLR, PLR and SII with frailty were found. During the 2-year follow-up, 180 (15.67%) individuals were new-onset frailty. After adjustment, an increased logNLR (odds ratio [OR] 2.92, 95% confidence interval [CI] 1.20–7.18), logPLR (OR 2.54, 95% CI: 1.01–6.53) and logSII (OR 2.34, 95% CI: 1.16–4.78) were significantly associated with a higher risk of incident frailty in all individuals. Additionally, the associations of logNLR (OR 4.21, 95% CI 1.54–11.62 logPLR (OR 3.38, 95% CI: 1.17–9.91) and logSII (OR 2.56, 95% CI: 1.15–5.72) with incident frailty were remained after excluding individuals with comorbidities. In further analyzed, individuals with higher levels of NLR and SII had higher risk of incident frailty when we stratified individuals by quartiles of these immunity markers.ConclusionNLR and SII are easily obtained immunity markers that could be used to predict incident frailty in clinical practice.

Social Vulnerability Predicts Frailty: Towards a Distinction between Fragility and Frailty?

All definitions of frailty converge in two aspects: the notion of loss or decline and the ability to predict negative health outcomes. Numerous factors were reported to be associated with frailty among which biological, psychological, economic and social factors. Whether the latter contribute at the same level is a relevant question, as social vulnerability does not refer to an ongoing process of decline leading a person to become frail but rather to a relativity stable state making the person fragile. Thus, social vulnerability should increase the risk of frailty. This study aims at assessing whether social vulnerability increases the risk of incident frailty. 1531 participants aged 65 or older from the PAQUID cohort study were included. Cox regression models tested the association between social vulnerability index (SVI, based on 28 social items) and frailty index (FI, based on 25 health-related items) over the 27 years of follow-up. Adjusted for age and sex, higher SVI was associated with increased risk of incident frailty (HR=3.85, 95% CI=1.87-7.94, p<.001). After additional control for IADL disability and comorbidities, higher SVI was associated with increased risk of frailty (HR=3.40, 95% CI=1.63-7.07, p<.05). The association remained significant after controlling for MMSE (HR=2.34, 95% CI=1.08-5.07, p<.05). Poor social status is a risk factor of frailty. From a conceptual point of view, our results claim for a distinction between the concepts of frailty and fragility, the first one being the consequence of an ongoing decline, the other one related to a relatively stable condition of fragility, mainly explained by unfavorable social conditions.

Towards Healthy Ageing: Using the Concept of Intrinsic Capacity in Frailty Prevention.

To examine whether intrinsic capacity (IC) could predict frailty, whether declines in specific domains of IC could lead to frailty, and whether different combinations of domains could represent different risks of developing frailty. Community. Chinese people aged 65 years and older. Using data from a prospective cohort study, we derived a summary score for IC and scores for the five domains (cognitive, locomotor, vitality, sensory, psychological) for each participant at baseline. Frailty was assessed according to the Fried's frailty phenotype at baseline, 2- and 4-year follow-ups. Participants were classified as frail if they had ≥3 of the following criteria: weight loss, self-rated exhaustion, weakness, slow walking speed, and low physical activity. Four thousand participants were interviewed at baseline. Overall mean age was 72.5 years; 50% were women. Between baseline and the 2-year follow-up, 5.7% of non-frail participants developed frailty; between 2- and 4-year follow-ups, 5.7% of non-frail participants developed frailty. The average annual incidence rate of frailty was 2.9%. Higher scores on IC at baseline were associated with a lower risk of incident frailty at both follow-ups (year 2, odds ratio (OR)=0.64, 95% confidence interval (CI)=0.59-0.71); year 4, OR=0.64, 95%CI=0.58-0.71) after adjustment for age, sex, educational level, and chronic diseases. Across the five domains, vitality was the strongest predictor of incident frailty at each follow-up (year 2, OR=0.33, 95%CI=0.24-0.45; year 4, OR=0.33, 95%CI=0.23-0.46). Compared to other combinations of any two domains, having 'high' scores on both vitality and locomotor domains was associated with the lowest risk of incident frailty (year 2, OR=0.11, 95%CI=0.06-0.22, area under the curve (AUC)=0.770; year 4, OR=0.18, 95%CI=0.10-0.32, AUC=0.782). This study provides evidence that IC was independently associated with incident frailty. It also finds that vitality was the domain most strongly associated with incident frailty. Finally, it suggests that optimizing multiple domains of IC, particularly vitality and locomotor, may prevent frailty.

The Effect of Low-Dose Aspirin on Frailty in Older Adults in the Aspirin in Reducing Events in the Elderly Study

There are no widely accepted pharmacologic treatments for frailty prevention. Since frailty is associated with inflammation, aspirin has the potential to reduce frailty. We investigated whether low-dose aspirin reduces incident frailty in participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. In the U.S and Australia, 19,114 healthy community-dwelling individuals aged ≥70 years (U.S. minorities ≥65 years) were enrolled in ASPREE, a double-blind, placebo-controlled trial of 100mg daily low-dose aspirin vs. placebo. Frailty was defined according to a modified Fried frailty definition, and a frailty index which used a deficit accumulation model. Competing risk Cox proportional hazards models were used to compare time to incident frailty for aspirin vs. placebo. At baseline, 2.2% and 8.1% met criteria for frailty by Fried and frailty index criteria, respectively. Over a median of 4.7 years of follow-up, 2252 participants developed incident frailty according to Fried classification, and 4376 according to the frailty deficit accumulation index. There was no difference in the risk of incident frailty between individuals randomized to aspirin versus placebo according to either criteria (Fried frailty HR: 1.03, 95% CI 0.97-1.09, p=0.41; frailty index HR: 1.03, 95% CI 0.97-1.10, p=0.29). Change in frailty over time was not different between the aspirin and placebo treatment arms. The results were consistent across a series of sub-groups, including baseline frailty status. Based on these results, aspirin use in healthy older adults does not reduce incident frailty.

Validation of the Integrated Care for Older People Screening Tool: Focus on the Chair Rise Test to Assess Locomotion

The Integrated Care for Older People (ICOPE) is a function- and person-centered healthcare pathway developed by the World Health Organization (WHO). ICOPE's first step (Step 1) consists of screening for impairments in the intrinsic capacity (IC) domains (namely sensorial, cognition, nutrition, psychological, and locomotion). For instance, the ICOPE Step1 tool suggests a cut-point of 14 seconds for five-repetition chair rise time as a marker of impaired locomotion. Given the lack of validation of this tool in the literature, we aimed to validate the ICOPE screening tool concerning incident health outcomes, focusing on the locomotion assessment. First, we analyzed the five-domain screening tool's ability to identify older adults (OA) at higher risk of incident outcomes (frailty, disability, dementia) using longitudinal data from the Multidomain Alzheimer Preventive Trial (MAPT). For the locomotion assessment (chair rise test), we derived and cross-validated age-specific cut points from two population-based cohorts using ROC (receiver operating characteristic) analysis. We further verified those cut points among OA real-life users of the health system and clinical trial participants. In conclusion, the ICOPE Step 1 screening tool was able to identify OA at higher risk of incident frailty, disability, and dementia. New chair-rise-time cut points for age groups 70-79 years old and 80 years and older were valid in populations from different settings. The ICOPE Step 1 tool provides a practical and integrative way of screening older adults for impairments in IC and detecting those at higher risk of functional decline.

The Effect of Low-Dose Aspirin on Frailty Phenotype and Frailty Index in Community-Dwelling Older Adults in the ASPirin in Reducing Events in the Elderly Study.

Frailty is associated with chronic inflammation, which may be modified by aspirin. The purpose of this study was to determine whether low-dose aspirin reduces incident frailty in healthy older adult participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. In the United States and Australia, 19 114 community-dwelling individuals aged ≥70 and older (U.S. minorities ≥65 years) and free of overt cardiovascular disease, persistent physical disability, and dementia were enrolled in ASPREE, a double-blind, placebo-controlled trial of 100-mg daily aspirin versus placebo. Frailty, a prespecified study end point, was defined according to a modified Fried frailty definition (Fried frailty) and the frailty index based on the deficit accumulation model (frailty index). Competing risk Cox proportional hazard models were used to compare time to incident frailty by aspirin versus placebo. Sensitivity analysis was conducted to include frailty data with and without imputation of missing data. Over a median 4.7 years, 2 252 participants developed incident Fried frailty, and 4 451 had incident frailty according to the frailty index. Compared with placebo, aspirin treatment did not alter the risk of incident frailty (Fried frailty hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.96-1.13; frailty index HR: 1.03, 95% CI 0.97-1.09). The proportion of individuals classified as frail, and the trajectory in continuous frailty scores over time, were not different between the aspirin and placebo treatment groups. The results were consistent across a series of subgroups. Low-dose aspirin use in healthy older adults when initiated in older ages does not reduce risk of incident frailty or the trajectory of frailty.

Cardiovascular risk score associations with frailty in men and women with or at risk for HIV.

To understand the relationship between cardiovascular disease (CVD) risk and frailty among men (MWH) and women living with HIV (WWH), or at risk for HIV. We considered 10-year coronary heart disease and atherosclerotic CVD risk by Framingham risk score (FRS, 2001 National Cholesterol Education Program Adult Treatment Program III) and Pooled Cohort Equations (PCE, 2013 American College of Cardiology/American Heart Association) in relation to the Fried Frailty Phenotype (FFP) in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS). FFP was ascertained in MACS from 2004 to 2019 and in WIHS from 2005 to 2006 and 2011-2019. FFP score at least three of five components defined frailty. Repeated measures logistic regression (both cohorts) and Cox proportional hazards regression (MACS) were performed, controlled for education, income, cholesterol medication and hepatitis C virus serostatus, and among MWH and WWH, CD4+ cell count/μl, antiretroviral therapy, and HIV viral load. There were 5554 participants (1265 HIV seronegative/1396 MWH; 768 seronegative/1924 WWH) included. Among men, high-risk FRS was associated with increased risk of incident frailty among seronegative [adjusted hazard ratio (aHR)) = 2.12, 95% confidence interval (CI):1.22-3.69] and MWH (aHR = 2.19, 95% CI: 1.33-3.61). Similar associations were seen with high-risk PCE and incident frailty among SN (aHR = 1.88, 95% CI: 1.48-2.39) and MWH (aHR = 1.59, 95% CI: 1.26-2.00). Among women, high-risk PCE was associated with frailty in SN [adjusted odds ratio (aOR) = 1.43, 95% CI: 1.02-2.00] and WWH (aOR = 1.36, 95% CI: 1.08-1.71); however, high-risk FRS was not (seronegative: aOR = 1.03, 95% CI: 0.30-3.49; WWH: aOR = 0.86, 95% CI: 0.23-3.20). Higher CVD risk was associated with increased frailty regardless of HIV serostatus among men and women. These findings may inform clinical practices of screening for frailty.