Frail Participants Research Articles

Assessment, Prevalence, and Correlates of Frailty among Moroccan People Aged 50 and above Living with HIV.

Persons living with HIV experience many challenges, such as premature aging and geriatric syndromes. Frailty has become an important determinant of a series of adverse health outcomes. This research aimed to evaluate the prevalence and risk factors for frailty in this population. A cross-sectional outpatient investigation was conducted in an urban HIV clinic. Patients aged 50 and older living with HIV were included. Frailty phenotype was evaluated using the original Fried criteria, and we calculated the Veterans Aging Cohort Study (VACS) index, Charlson Comorbidity Index, Fracture Risk Assessment Tool scores, and Mini-mental State Exam scores. One hundred and nine individuals were studied. Ninety-two (84.4%) were men, with a mean age of 57.65.2 years. Fourteen (12.8%) participants were frail. Frail participants were older (P = 0.001) and less likely to be virally suppressed (P = 0.01). Having ≥3 comorbidities, VACS index, polypharmacy, and 5-year mortality risk was significantly greater in the frail group. Frailty was significantly associated with poorer quality of life (P = 0.02). The cognitive impairment, falls, and malnutrition risk were significantly associated with a risk to manifest a frail phenotype. Frailty is common among Moroccans with HIV, and it is associated with greater morbidity and mortality rates. Our findings should serve as a warning sign to standardize frailty and geriatric syndrome screening in this population.

Joint Association of Physical Frailty and Self-Rated Health With Mortality Among Community-Dwelling Older Adults.

The relationship between subjective and objective health is complex and not always matched. Although frailty and self-rated health (SRH) have been separately associated with adverse outcomes, their joint effects remained unclear. Participants were 5300 adults ≥60 years from the China Health and Retirement Longitudinal Study in 2011. Frailty, measured by the validated physical frailty phenotype approach, was classified as nonfrail, prefrail, and frail. SRH was categorized into 3 groups: excellent/very good/good, fair, and poor/very poor. We used the Cox models to examine the independent and joint association of frailty and SRH with mortality. We used the interaction approach to determine whether the association of SRH with mortality differed by frailty. Subgroup analyses were conducted by depression and cognitive impairment. About 8.1% of frail participants reported excellent/very good/good health; 21.2% of the nonfrail reported poor/very poor health. Prefrailty and frailty were associated with a 1.63- and 2.38-fold increase in the hazard of mortality than the nonfrail, respectively, after adjusting for SRH. Reporting fair and poor/very poor health was associated with a 29% and 100% increase in the hazard of mortality, respectively, after adjusting for frailty. No significant interaction was found. Prefrail and frail older adults with excellent/very good/good health had a similar mortality as the nonfrail with poor/very poor SRH. The association of SRH with mortality was less pronounced among individuals with depression or cognitive impairment. SRH is a potential marker of resilience among people living with frailty that may be a target for ameliorating health risks induced by frailty.

ASSOCIATIONS BETWEEN FRAILTY AND SLEEP IN OLDER ADULTS WITH CANCER TREATED WITH CHEMOTHERAPY

Abstract Little is known about the association between frailty and sleep after starting chemotherapy. The goal of this study was to examine frailty and sleep in older adults (65+ years old) with cancer. Patients newly diagnosed with cancer and starting chemotherapy were recruited to a multi-site study. Participants completed questionnaires before chemotherapy (i.e., baseline) and 5 days after their first infusion. A pre-treatment frailty score was derived using a 59-item deficit accumulation index and dichotomized (frail vs. robust). Sleep was assessed with the PROMIS Sleep Disturbance 8a (difficulty sleeping) and Sleep Impairment 8a (daytime sleepiness). Repeated measures ANOVAs adjusted for age, sex, cancer stage, and cancer type evaluated change in sleep over time. Participants were 402 older adults with cancer (M age=72, SD=5). Most were female (65%), non-Hispanic (96%), and married (67%). Difficulty sleeping was higher in frail participants (26%) than robust participants at baseline (p< 0.001). Over time, difficulty sleeping decreased in frail participants but increased in robust participants (p=0.02). Difficulty sleeping remained higher in frail participants post-infusion (p=0.01). Daytime sleepiness at baseline did not differ by frailty status (p=0.86) and was higher than population norms. Frail participants reported smaller reductions in daytime sleepiness over time (p< 0.01), and more daytime sleepiness after infusion (p< 0.0001) than robust participants. Despite improvements in sleep from pre-treatment to 5 days after infusion, frail participants reported more difficulty sleeping and daytime sleepiness than robust participants after infusion. Additional research is needed to better understand the association of frailty with health outcomes in older adults with cancer.

DISENTANGLE THE RELATION BETWEEN FRAILTY, SELF-RATED HEALTH, AND DEATH: IMPLICATIONS FOR RESILIENCE

Abstract Frail older adults represent a heterogeneous group. Identifying factors predictive of adverse outcomes among this group could advance our understanding of ways to withhold the devastating effects of frailty. Self-rated health (SRH) is a valuable health measure among the general population. However, it is unknown whether SRH remains predictive among the frail. We examined the joint association of frailty and SRH with mortality and assessed the association between SRH and death among the frail. Data were from the UK Biobank, a large-scale cohort study comprising 0.5 million individuals. At baseline, participants were assessed for physical frailty (non-frail, prefrail, and frail) and SRH (excellent/good, fair, and poor). The Poisson model was used to address the study’s aims. Age, sex, education, marital status, and smoking were adjusted. Of 488,590 participants, 3.2% were frail, and 4.3% reported poor health. Although frail participants were more likely to report poor health, 19.7% of the frail reported excellent/good health, and 15.9% of the non-frail reported fair or poor health. SRH was strongly associated with death among the non-frail, prefrail, and frail subgroups. Among frail participants, reporting fair and excellent/good was associated with a 17% and 25% lower hazard of death. The association between SRH and death was stronger among the frail than the non-frail, although the interaction term was insignificant. Future investigation into the determinants of positive SRH despite being frail could provide new targets for intervention to improve resilience and risk screening of downstream outcomes in the most vulnerable.

LIFESTYLE CHANGES AFTER FRAILTY ONSET AMONG MIDDLE-AGED AND OLDER ADULTS IN THE UNITED STATES

Abstract Frailty could be the teachable moment to promote a lifestyle change for middle-aged and older adults. This study aimed to investigate the impact of sociodemographic characteristics on lifestyle changes among frail adults aged ≥50 years. A total of 5,440 frail individuals aged ≥50 years from the Health and Retirement Study (HRS) 2004-2020 were included. The Paulson–Lichtenberg Frailty Index was used to measure frailty. Lifestyle included smoking status, alcohol consumption, physical activity, and sleep problems. Logistic regression models were used to examine the associations between sociodemographic characteristics and lifestyle change among frail participants. After frailty, a higher proportion of individuals reported maintaining their smoking and drinking status without change. Compared to increased physical activity, more people reported reducing their low, moderate, and high-intensity physical activity. Similarly, a greater proportion of individuals reported worsened sleep problems compared to those who experienced improvements in sleep problems. Age was negatively associated with quitting smoking and increased light, moderate, as well as vigorous physical activity, while was positively associated with improving sleep problems. Males were more likely to quit smoking, quit drinking, and increase light physical activity. Individuals with medium and high education levels were more likely to quit drinking and less likely to increase moderate physical activity. A sensitivity analysis based on the 4-year interval between pre-diagnosis and post-diagnosis of frailty showed that being unmarried was associated with an increased likelihood of quitting smoking. Some people reported lifestyle changes after frailty. Age, gender, marital status, and education levels may affect lifestyle changes after frailty.

Association of coexistence of frailty and depressive symptoms with mortality in community-dwelling older adults: Kashiwa Cohort Study

ObjectivesThis study aimed to determine the longitudinal associations of the coexistence of frailty and depressive symptoms with mortality among older adults. MethodsThe study participants were community-dwelling older adults aged ≥65 years who participated in the baseline survey of the Kashiwa Cohort Study in Japan in 2012. We used Fried's frailty phenotype criteria to classify participants as non-frail (score = 0), pre-frail (1 or 2), or frail (≥3). Depressive symptoms were assessed using the GDS-15 (≥6 points). Cox proportional hazards models were used to evaluate the association of co-occurring frailty and depressive symptoms with all-cause mortality, after adjusting for sociodemographic and clinical characteristics. ResultsThe study included 1920 participants, including 810 non-frail, 921 pre-frail, and 189 frail older adults, of which 9.0 %, 15.7 %, and 36.0 %, respectively, had depressive symptoms. Ninety-one (4.7 %) participants died during the average follow-up period of 4.8 years. Compared with non-frail participants without depressive symptoms, frail participants had greater adjusted hazard ratios for mortality: 2.47 (95 % CI, 1.16 to 5.25) for frail participants without depressive symptoms and 4.34 (95 % CI, 1.95 to 9.65) for frail participants with depressive symptoms. However, no statistically significant associations were observed in non-frail or pre-frail participants irrespective of depressive symptoms. ConclusionFrail older adults with depressive symptoms have a substantially greater risk of mortality. Screening for depressive symptoms and frailty in older adults should be incorporated into health checkups and clinical practice to identify high-risk populations.

IS FRAILTY THE END? ASSOCIATION OF LIFESTYLES AND SOCIAL ENVIRONMENT WITH DEATH AMONG THE FRAIL

Abstract Despite many efforts, reversing the frail status among older adults remains difficult. However, frailty does not mean the end of life. Adherence to a healthy lifestyle and a desirable social environment may reduce the risk of adverse outcomes among the frail. We examined whether adherence to a healthy lifestyle was associated with lower all-cause mortality and the joint association of lifestyles and social environment with mortality among the frail. Data were from UK Biobank; 15,594 physically frail middle-aged and older adults were included. Frailty was assessed by Fried’s physical frailty phenotype approach. We created a composite healthy lifestyle score using four lifestyle factors: smoking, alcohol consumption, physical activity, and diet. We used 17 social factors to construct a polysocial score for measuring the social environment. We used the Cox model to estimate the association of each lifestyle factor and the composite lifestyle score with mortality among the entire sample and by polysocial score (low, intermediate, and high level). We also evaluated the joint association of lifestyle and polysocial scores with mortality. Frail participants with a healthy level of smoking, physical activity, diet, and composite lifestyle score had a 40%, 33%, 15%, and 34% lower hazard of death than those with an unhealthy level, respectively. We found a joint effect of a healthy lifestyle and social environment on mortality. Adherence to a healthy lifestyle may provide an opportunity to decrease the risk of adverse health outcomes among the frail, especially among those living in an unfavorable social environment.

MUSCLE UP: WHAT AGING LOOKS LIKE FROM THE INSIDE OUT

Abstract The Longitudinal Studies Section of the Translational Gerontology Branch of the National Institute on Aging Intramural Research Program has the mission and opportunity to examine aging physiology from the cellular to the full body functional level in model systems and human populations. This symposium presents ongoing research that targets pathologic and normative change in muscle with aging and the significance of these changes for understanding the aging process. Data come from the Baltimore Longitudinal Study of Aging (BLSA) and the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT) study. In nearly 500 BLSA participants aged 50+, Zenobia Moore evaluates the association between multiple epigenetic age metrics and change over 6 years in mid-femur areas of muscle and subcutaneous and intramuscular fat derived from computed tomography. Qu (Teresa) Tian investigates the relationship between skeletal muscle mitochondrial function and risk of MCI or dementia over 3.3 years in 460 initially cognitively normal BLSA participants and PET and blood biomarkers of AD in available subsamples. In 82 men and women from GESTALT, Stefano Donega examines relationships between physical activity, peak oxygen consumption and muscle oxidative capacity using p31 MR spectroscopy and gene expression, transcript usage and splicing events derived from vastus lateralis biopsies. Using volumetric Focused Ion Beam Scanning Electron Microscopy, Lisa Hartnell shares 3D images of muscle samples at the level of the mitochondrial reticulum and sarcomere from young and old healthy and frail GESTALT participants. Together, these findings highlight the value of muscle as a window on aging.

Moving towards the detection of frailty with biomarkers: A population health study.

Aging adults experience increased health vulnerability and compromised abilities to cope with stressors, which are the clinical manifestations of frailty. Frailty is complex, and efforts to identify biomarkers to detect frailty and pre-frailty in the clinical setting are rarely reproduced across cohorts. We developed a predictive model incorporating biological and clinical frailty measures to identify robust biomarkers across data sets. Data were from two large cohorts of older adults: "Invecchiare in Chianti (Aging in Chianti, InCHIANTI Study") (n = 1453) from two small towns in Tuscany, Italy, and replicated in the Atherosclerosis Risk in Communities Study (ARIC) (n = 6508) from four U.S. communities. A complex systems approach to biomarker selection with a tree-boosting machine learning (ML) technique for supervised learning analysis was used to examine biomarker population differences across both datasets. Our approach compared predictors with robust, pre-frail, and frail participants and examined the ability to detect frailty status by race. Unique biomarker features identified in the InCHIANTI study allowed us to predict frailty with a model accuracy of 0.72 (95% confidence interval (CI) 0.66-0.80). Replication models in ARIC maintained a model accuracy of 0.64 (95% CI 0.66-0.72). Frail and pre-frail Black participant models maintained a lower model accuracy. The predictive panel of biomarkers identified in this study may improve the ability to detect frailty as a complex aging syndrome in the clinical setting. We propose several concrete next steps to keep research moving toward detecting frailty with biomarker-based detection methods.

Diet Quality and Incident Frailty in Adults 65 Years or Older: The Israeli Longitudinal Study on Aging.

To prospectively examine the association between diet quality and frailty incidence in the oldest-old age group. We studied an older adult (65+ years) cohort participating in the Israeli National Health and Nutrition Survey of Older Adults in 2005-2006 (T1 [N=1799]). Survivors of T1 were contacted, and between 2017 and 2019, an extensive interview and a functional assessment were conducted (T2) of 604 past participants. A 24-hour dietary recall, assessed at T1, was used to calculate the Healthy Eating Index (HEI-2015) score. A frailty index based on an accumulation of deficits, including clinical, functional, and cognitive measures, was computed. Frail participants at T1 were excluded from the analysis. Logistic regression models were constructed to assess the association of HEI-2015 score with frailty incidence. Inverse probability weighting was used to minimize selection bias due to attrition. Of the 479 T2 participants analyzed (mean [SD] age, 84 [5] years; 50% women), 225 (46%) were classified as frail. Frail participants were older, were less educated, and had a lower household income and a higher comorbidity burden at baseline than non-frail participants. After adjustment for sociodemographic and lifestyle factors, a higher HEI-2015 score was associated with decreased odds of incident frailty (odds ratio, 0.57 [95% CI, 0.35 to 0.91] for the upper tertile and 0.66 [95% CI, 0.42 to 1.06] for the middle tertile compared with the lower tertile; Ptrend=.02). In this cohort study of oldest-old participants, improved diet quality was inversely associated with frailty incidence in a dose-dependent manner.

Frailty and chronic kidney disease: associations and implications.

Frailty and its association with chronic kidney disease (CKD) has been established previously. The present study examined this association further by studying the distribution of frailty among groups defined by different stages of the disease. It also identified associated health deficits and explored their association with estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR). A cross-sectional survey was conducted on 90 non-dialysis dependent CKD Stage 1-4 patients, recruited in three stratified groups of 30 participants each based on the stage of disease. Frailty was assessed using Fried's frailty criteria and associated health deficits were recorded using a pre-determined list. Depression was screened using a 4-point depression scale. 21.1% of the participants were frail and 43.3% were pre-frail. The proportion of frailty in CKD groups A (Stages 1 and 2), B (Stage 3a), and C (Stages 3b and 4) was 10%, 13.3%, and 40%, respectively. The association of health deficits including co-morbidities, physical parameters, mental status, daily activities, etc. with UACR, eGFR, and CKD stages was not statistically significant. Nearly one in two frail participants was depressed compared with 14% among non-frail participants. The skewed distribution of 21% frail subjects identified in our study indicates an association between frailty and advancing kidney disease. Frail individuals had a lower eGFR, higher UACR, were more likely to be depressed, and had higher count of health deficits and poorer performance on Barthel Index of Activities of Daily Living and WHOQOL. Early identification of depression would improve care in these patients.

Why are older adults living with the complexity of multiple long-term conditions, frailty and a recent deterioration in health under-served by research? A narrative synthesis review of the literature.

Older adults living with the complexity of multiple long-term conditions (MLTC), frailty and a recent deterioration in health are under-served by research. As a result, current treatment guidelines are often based on data from studies of younger and less frail participants, and often single disease focused. The aims of this review were (i) to identify why older adults living with the complexity of MLTC, frailty and a recent deterioration in health are under-served by research and (ii) to identify strategies for increasing their recruitment and retention. Although a range of factors have been suggested to affect the participation of older adults with MLTC and frailty in research, this review shows that much less is known about the inclusion of older adults living with the complexity of MLTC, frailty and a recent deterioration in health. Researchers should focus on strategies that minimise participation burden for these patients, maintaining an adaptive and flexible approach, to increase their recruitment and retention. Future research should include qualitative interviews to provide further insights into how best to design and conduct research to suit the needs of this population group.

Baseline Frailty and Domain‐specific Cognitive Declines in Healthy and MCI Older Adults

AbstractBackgroundBoth physical frailty and cognitive decline increase with age and each place adults at elevated risk for loss of independence. Inconsistent associations have been found between frailty and risk for cognitive declines across cognitive domains. However, most studies were cross‐sectional and did not include a comprehensive battery of neuropsychological tests. We hypothesized that frail older adults, whether with or without Mild Cognitive Impairment (MCI) at baseline, are at risk for accelerated domain‐specific cognitive declines.MethodThe Ginkgo Evaluation of Memory Study (GEMS) was a prospective study of 3069 dementia‐free older adults aged 72‐96 years, followed for up to 7.5 years or a diagnosis of dementia, 482 of whom were diagnosed with MCI at baseline. A modified physical frailty phenotype was constructed using GEMS baseline data. A Neuropsychological Battery consisted of 13 tests reflecting global cognition, memory, visual‐spatial construction, language, psychomotor speed/attention, and executive function were administered annually. Linear random effects models were used to compare differences in baseline and rate of change in domain scores among individuals with and without baseline frailty.ResultOverall, frail participants showed poorer baseline cognitive function in all domains, and greater declines in all cognitive domains. When stratified by baseline MCI, among non‐MCI participants, those with frailty revealed poorer baseline psychomotor speed/attention and executive function, and greater declines in all cognitive domains. Among MCI participants, those with frailty exhibited lower baseline visual‐spatial construction, and greater declines in all cognitive domains except for visual‐spatial construction and executive function. In all cognitive domains, the estimated effect of frailty on cognitive decline was greater in MCI participants than non‐MCI participants.ConclusionFrailty was predictive of accelerated cognitive declines across domains and more so in those with baseline MCI. The results from this study highlight the importance of assessing frailty as a risk factor for accelerated cognitive declines, particularly among those at elevated preclinical cognitive risk. These individuals may be at the greatest risk of transitioning to dementia.

Handle with care: frailty complicates cognitive outcomes in older adults with delirium

AbstractBackgroundDelirium has been associated with long‐term cognitive impairment and dementia (1), and frailty is a known risk factor for incident dementia in older adults (2). However, it remains unclear whether delirium and frailty synergistically affect cognitive decline. We investigated whether frailty modifies the association between delirium and post‐discharge dementia in older adults.MethodsWe completed a cohort study including acutely ill older adults admitted to a tertiary university hospital (2010‐2016). Our inclusion criteria were: age ≥60 years; no preexisting cognitive decline; ≥12 months of follow‐up after discharge. Preexisting cognitive decline was identified using clinical history, CDR‐SB, and IQCODE‐16. Delirium was defined using the Short‐CAM. Frailty was defined using the FRAIL scale and the Frailty Index. Our primary outcome was the incidence of post‐discharge dementia, identified in follow‐up medical records. We investigated the association between delirium and post‐discharge dementia using competing‐risks regression models. We then completed interaction analyses exploring the effect of frailty on the association between delirium and post‐discharge dementia.ResultsWe included 309 participants (mean age = 78 years; female = 60%). We detected delirium in 66 (21%) hospitalizations and incident dementia in 59 (19%). Overall, 16% of the patients were classified by FRAIL as robust, 55% as prefrail, and 29% as frail. After multivariable analysis, we found that delirium was independently associated with incident dementia, but the association was significantly modified by frailty (p = 0.009) (Figure 1). The adjusted sub‐hazard ratio (SHR) in non‐frail participants was 1.14 (95%CI = 0.53‐2.44) and 3.80 (95%CI = 1.80‐8.05) in frail participants Tables 1‐2).ConclusionFrailty was a significant modifier of the association between delirium and post‐discharge dementia in this population. Research on frailty interventions should measure delirium incidence and long‐term cognitive decline to explore their potential impact on these outcomes.

Association between frailty and sleep quality in people living with multiple sclerosis and obesity: An observational cross-sectional study

BackgroundA majority of the people with multiple sclerosis (pwMS) experience sleep disturbances. Frailty is also common in pwMS. The geriatric literature strongly suggests that frailty is associated with worse sleep outcomes in community-dwelling older adults, but this association has yet to be explored among pwMS. This study focused on examining the association between frailty and sleep quality in pwMS. MethodsSeventy-six people with both MS and obesity (mean age: 47.6 ± 10.9 years, 81.6 % female, mean body mass index (BMI): 37.10 ± 5.5 kg/m2, mean Patient Determined Disease Steps (PDDS): 0.82 ± 1.20) were included in this cross-sectional secondary analysis. A comprehensive frailty index (FI) based on 41 health deficits from various health domains was calculated based on standardized procedures. Sleep quality was determined by the Pittsburgh Sleep Quality Index questionnaire (PSQI). ResultsOverall, 67.1 % of the participants were identified as non-frail (FI ≤ 0.25), and 32.9 % were identified as frail (FI > 0.25). A significant correlation was observed between FI scores and global PSQI scores (ρ = 0.43, p < 0.05). Cross-tabulation analyses revealed that frail participants had worse subjective sleep quality, sleep latency, habitual sleep efficiency, sleep disturbances, daytime dysfunction, and higher use of sleep medications compared to non-frail participants (p < 0.05). ConclusionsThe current study identified a significant association between frailty and sleep quality in people with both MS and obesity with minimal disability. These findings underscore the importance of untangling the relationship between frailty and sleep quality in pwMS. These results could lead to a more targeted approach for rehabilitation interventions aiming to improve frailty in MS.

Association of Physical Frailty and Cognitive Function in a Population-Based Cross-Sectional Study of American Older Adults

Introduction: Cognitive impairment and frailty are prevalent in older persons. Physical frailty is associated with cognitive decline; however, the role of effect modifiers such as age, sex, race/ethnicity, and cognitive reserve is not well understood. Methods: Cross-sectional data from the National Health and Nutrition Examination Survey (2011–2014) were obtained for participants aged ≥60 years. Complete availability of cognitive scores was an inclusion criterion. Physical frailty was defined by the presence of exhaustion, weakness, low body mass, and/or low physical activity, and categorized into three groups: robust (0 present), pre-frail (1–2 present), or frail (3–4 present). Four cognitive test scores were converted to z-scores, and global cognition (composite z-score) was calculated by averaging the four-individual z-scores. Multivariable linear regression models were fit to estimate the associations between frailty and cognitive function. Frailty was also evaluated as a risk factor for self-reported subjective memory complaint (SMC) using logistic regression. All models were adjusted for age, sex, race/ethnicity, education, alcohol use, income, marital status, diabetes, hypertension, and history of stroke. Effect measure modification analyses were conducted by age, sex, race/ethnicity, education, and occupational cognitive demand. Results: The study population comprised 2,863 participants aged ≥60 years. 50.6% of the participants were categorized into robust, 43.2% pre-frail, and 6.2% frail. After adjusting for covariates, compared to robust participants, frail and prefrail participants had lower adjusted mean global cognitive z-scores, <inline-formula><mml:math id="m1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mi>β</mml:mi><mml:mo>^</mml:mo></mml:mover></mml:mrow></mml:math></inline-formula> = −0.61, 95% CI: −0.83, −0.38 and <inline-formula><mml:math id="m2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mi>β</mml:mi><mml:mo>^</mml:mo></mml:mover></mml:mrow></mml:math></inline-formula> = −0.21, 95% CI: −0.30, −0.12, respectively. Both prefrail and frail participants had higher odds of SMC compared to the robust participants. We did not see strong evidence that the association between frailty and cognition was modified by the factors we studied. Discussion/Conclusion: Both pre-frailty and frailty were associated with lower cognitive performance and were more likely to report subjective memory complaints relative to persons without frailty. These findings provide additional evidence that physical frailty may serve as a prognostic factor for cognitive deterioration or dementia, and prevention of frailty may be an important public health strategy.

A prospective, observational study of frailty, quality of life and dialysis in older people with advanced chronic kidney disease

BackgroundFrailty is prevalent in older people with chronic kidney disease (CKD) and robust evidence supporting the benefit of dialysis in this setting is lacking. We aimed to measure frailty and quality of life (QOL) longitudinally in older people with advanced CKD and assess the impact of dialysis initiation on frailty, QOL and mortality.MethodsOutpatients aged ≥65 with an eGFR ≤ 20ml/minute/1.73m2 were enrolled in a prospective observational study and followed up four years later. Frailty status was measured using a Frailty Index (FI), and QOL was evaluated using the EuroQol 5D-5L instrument. Mortality and dialysis status were determined through inspection of electronic records.ResultsNinety-eight participants were enrolled. Between enrolment and follow-up, 36% of participants commenced dialysis and 59% died. Frailty prevalence increased from 47% at baseline to 86% at follow-up (change in median FI = 0.22, p < 0.001). Initiating dialysis was not significantly associated with change in FI. QOL declined from baseline to follow-up (mean EQ-5D-5L visual analogue score of 70 vs 63, p = 0.034), though commencing dialysis was associated with less decline in QOL. Each 0.1 increment in baseline FI was associated with 59% increased mortality hazard (HR = 1.59, 95%CI = 1.20 to 2.12, p = 0.001), and commencing dialysis was associated with 59% reduction in mortality hazard (HR = 0.41, 95%CI = 0.20 to 0.87, p = 0.020) irrespective of baseline FI.ConclusionsFrailty increased substantially over four years, and higher baseline frailty was associated with greater mortality. Commencing dialysis did not affect the trajectory of FI but positively influenced the trajectory of QOL from baseline to follow-up. Within the limitations of small sample size, our data suggests that frail participants received similar survival benefit from dialysis as non-frail participants.

OVCH1 Antisense RNA 1 is differentially expressed between non-frail and frail old adults.

While some old adults stay healthy and non-frail up to late in life, others experience multimorbidity and frailty often accompanied by a pro-inflammatory state. The underlying molecular mechanisms for those differences are still obscure. Here, we used gene expression analysis to understand the molecular underpinning between non-frail and frail individuals in old age. Twenty-four adults (50% non-frail and 50% frail) from InCHIANTI study were included. Total RNA extracted from whole blood was analyzed by Cap Analysis of Gene Expression (CAGE). CAGE identified transcription start site (TSS) and active enhancer regions. We identified a set of differentially expressed (DE) TSS and enhancer between non-frail and frail and male and female participants. Several DE TSSs were annotated as lncRNA (XIST and TTTY14) and antisense RNAs (ZFX-AS1 and OVCH1 Antisense RNA 1). The promoter region chr6:366,786,54-366,787,97;+ was DE and overlapping the longevity CDKN1A gene. GWAS-LD enrichment analysis identifies overlapping LD-blocks with the DE regions with reported traits in GWAS catalog (isovolumetric relaxation time and urinary tract infection frequency). Furthermore, we used weighted gene co-expression network analysis (WGCNA) to identify changes of gene expression associated with clinical traits and identify key gene modules. We performed functional enrichment analysis of the gene modules with significant trait/module correlation. One gene module is showing a very distinct pattern in hub genes. Glycogen Phosphorylase L (PYGL) was the top ranked hub gene between non-frail and frail. We predicted transcription factor binding sites (TFBS) and motif activity. TF involved in age-related pathways (e.g., FOXO3 and MYC) shows different expression patterns between non-frail and frail participants. Expanding the study of OVCH1 Antisense RNA 1 and PYGL may help understand the mechanisms leading to loss of homeostasis that ultimately causes frailty.

High blood galectin-3 level associated with risk of frailty in aging.

Frailty is one of the most problematic expressions of population aging, but its underlying mechanism has not been fully elucidated. Circulating galectin-3 (Gal-3) is involved in the pathogenesis of many age-related diseases. This study aims to explore the influence of circulating Gal-3 on the regulation of frailty and aging and to identify the potential mechanism further. In this cross-sectional analysis, the Fried frailty phenotype (FP) was assessed among 149 community elderly residents in Shanghai. Peripheral blood mononuclear cells (PBMCs) were isolated by the Ficoll-Paque density gradient method, and differentially expressed genes (DEGs) encoding transcription factors in frailty were detected by Illumina and bioinformatics analyzed with R software. Gene Ontology (GO) enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore the functional roles of these DEGs and the target genes related to frailty phenotypes. The serum Gal-3 concentration was tested by enzyme-linked immunosorbent assay (ELISA). Mouse frailty phenotype was used to construct an in vivo model of frailty, after which the serum levels of circulating Gal-3 and its gene expression levels in mouse tissues were determined. Participants' mean age was 72.04 ± 7.05 years. In total, 21.48% were frail and 36.91% were pre-frail. The mean serum Gal-3 concentration was 46.34 ± 17.99 ng/mL in frail participants, 32.30 ± 8.14 ng/mL in pre-frail participants, and 26.00 ± 5.87 ng/mL in non-frail individuals (p < 0.001). Significant positive correlations between serum Gal-3 level and FP score, SARC-F score, C-reactive protein (CRP), interleukin-6, etc., were observed. In addition, the KEGG pathway and GO enrichment analyses showed that 265 DEGs in PBMCs of frail participants were mainly related to inflammatory response, translation, RNA binding, protein binding, ribosome, and primary immunodeficiency. LGALS3 was identified as the overlapping gene between frailty-related DEGs and aging-related DEGs. The elevated serum Gal-3 concentration in the in vivo model of frailty was consistent with the results in participants. In both community-dwelling older adults and aged mice, serum Gal-3 concentration was positively correlated with frailty. This circulating mediator may be a promising indicator of frailty. Chinese Clinical Trial Registry identifier, ChiCTR2000036399.

Health factors associated with cognitive frailty in older adults living in the community.

This study aims to investigate the health factors associated with cognitive frailty in frail and pre-frail older adults living in the community. A total of 233 older adults meeting Fried's criteria for pre-frailty or frailty were included. Cognitive status was evaluated using the Short Portable Mental Status Questionnaire. Health factors encompassed nutritional status (evaluated using the Mini Nutritional Assessment tool, body mass index, and waist, arm, and leg circumferences), physical function (assessed with the Short Physical Performance Battery), quality of life (measured with the total index of the EuroQoL 5-Dimension 5-Level questionnaire - EQoL-Index -, and the Visual-Analogue Scale - QoL-VAS - for today's health state), as well as sleep, physical activity, and inactivity estimated through wrist-worn accelerometers. Multivariable logistic regression analyses were conducted to identify potential predictors of cognitive frailty, considering age as a confounding factor. Cognitive frail participants exhibited advanced age, heightened self-reported exhaustion, diminished overall physical performance, reduced leg perimeter, decreased engagement in moderate-to-vigorous physical activity, and higher levels of inactivity (all p<0.05). However, after adjusting for age, only QoL-VAS emerged as a cognitive frailty risk factor (Odds ratio: 1.024), while the EQoL-Index, calf perimeter, and levels of moderate-to-vigorous physical activity were identified as protective factors (Odds ratios: 0.025, 0.929, and 0.973, respectively). This study highlights the complex relationship between non-modifiable factors such as age, and modifiable factors including quality of life, nutritional status, and physical activity in the development of cognitive frailty among older adults with a frailty phenotype living in the community.