Cause Of Frailty Research Articles

#363 Altered filtration of middle-sized molecules is related to cardiovascular disease-related proteins

Abstract Background and Aims Cardiovascular (CV) complications, driven by complex vascular-metabolic interactions, are the leading cause of frailty in chronic kidney disease (CKD) complications. Advancing knowledge on cardio-renal interactions is a key to preventive and treatment strategies. Still, the cost-effective tools and biomarkers for early detection of altered glomerular filtration that subsequently leads to accelerated cardiovascular aging and, thus, higher CV mortality are lacking. Our objective was to investigate how molecules of varying masses, specifically cystatin C and creatinine, are filtered in kidney in relation to variations of plasma protein levels that might accelerate vascular changes, ultimately leading to early vascular aging and chronic kidney disease (CKD). Method From the Malmo Diet Cancer cohort, 4426 out of the 5061 participants had cardiovascular and renal biomarkers measured (mean age of 57 ± 6 years). These biomarkers included factors related to tissue growth and repair (EGFR), matrix metalloproteinases (MMP-12), proinflammatory cytokines (TNF-R1, TNF-R2, CXCL13, CXCL5), markers of vascular repair (SCF), homeostatic cytokines (CCL19), anti-apoptotic proteins (REG-4), adipokines (FABP4, LEP), as well as other cardiovascular proteins (NT-pro-BNP, MB) and indicators of kidney function. These 13 proteins were analyzed using multiplex proximity extension assay (Olink Cardiovascular II and Oncology panels), and have molecular masses either like creatinine (0.113 kDa) or cystatin C (13.3 kDa). These proteins were previously shown to be associated with measured glomerular filtration rate (mGFR) by Christensson A et al. (Proteomics Clin App, 2018). Kidney function was estimated by using cystatin C (CAPA, CKD-EPIcys) and creatinine (Lund-Malmo revised, CKD-EPIcr) equations. The filtration ratio was presented as CAPA/LMrev and CKD-EPIcys/CKD-EPIcr. The subgroups of this ratio were <0.70. Results Mean kidney function was as follows: 65 (±15)/ 69 (±16)/ 78 (±13) and 76 (±14) mL/min/1.73 m2 (CAPA/ CKD-EPIcys/ LMrev and CKD-EPIcr, respectively). The CAPA/LMrev filtration ratio was 0.84 (±0.18), whereas CKD-EPIcys/cr was 0.91 (±0.19). The filtration ratio negatively correlated with TNF-R1, TNF-R2, SCF, MMP-12, FABP4, LEP, NT-pro-BNP, CCL19, CXCL5, CXCL13 and REG-4; positively to EGFR and MB (all p < 0.001). In the whole cohort, participants with filtration ratio below 0.7 had significantly higher levels of TNF-R1, TNF-R2, MMP12, FABP4, LEP, NT-pro-BNP, CCL19, REG-4, and CXCL13, but similar levels of EGFR. CXCL5 and SCF levels were higher at <0.70 compared to 0.84-0.99 and >1.0 (Fig. 1). Interestingly, in women, MB was highest at <0.70; SCF level was higher at <0.70 compared to 0.84-0.99 and >1.00; EGFR level was highest at 0.70-0.84 compared to 0.84-0.99. In men, higher FABP4, LEP, CCL19, and MB were observed at <0.70 compared to 0.84-0.99 and >1.00. Conclusion Altered glomerular filtration for middle-sized molecules is related to the accumulation of plasma proteins that have similar molecular mass to creatinine and cystatin C and have sex-specific patterns. The proteins studied have been previously shown to contribute to vascular aging, cardiac damage and remodeling, and chronic kidney disease, and thus enlighten complex mechanisms behind cardio-renal interactions.

Machine Learning-Based Decision-Making in Geriatrics: Aging Phenotype Calculator and Survival Prognosis.

Aging is a natural process with varying effects. As we grow older, our bodies become more susceptible to aging-associated diseases. These diseases, individually or collectively, lead to the formation of distinct aging phenotypes. Identifying these aging phenotypes and understanding the complex interplay between coexistent diseases would facilitate more personalized patient management, a better prognosis, and a prolonged lifespan. Many studies distinguish between successful aging and frailty. However, this simple distinction fails to reflect the diversity of underlying causes. In this study, we sought to establish the underlying causes of frailty and determine the patterns in which these causes converge to form aging phenotypes. We conducted a comprehensive geriatric examination, cognitive assessment, and survival analysis of 2,688 long-living adults (median age = 92 years). The obtained data were clustered and used as input data for the Aging Phenotype Calculator, a multiclass classification model validated on an independent dataset of 96 older adults. The accuracy of the model was assessed using the receiver operating characteristic curve and the area under the curve. Additionally, we analyzed socioeconomic factors that could contribute to specific aging patterns. We identified five aging phenotypes: non-frailty, multimorbid frailty, metabolic frailty, cognitive frailty, and functional frailty. For each phenotype, we determined the underlying diseases and conditions and assessed the survival rate. Additionally, we provided management recommendations for each of the five phenotypes based on their distinct features and associated challenges. The identified aging phenotypes may facilitate better-informed decision-making. The Aging Phenotype Calculator (ROC AUC = 92%) may greatly assist geriatricians in patient management.

Research progress of relationship in long-novel coronavirus syndrome and sarcopenia

At present, the major public health challenges caused by novel coronavirus infection have gradually subside. However, a large number of people are still suffering from long-novel coronavirus syndrome or post-novel coronavirus syndrome. The clinical manifestations of long coronavirus syndrome are related to multiple systems, such as respiratory, circulatory, nervous, digestive and musculoskeletal systems, with various long-term persistent symptoms after novel coronavirus infection. At the same time, the infection of the novel coronavirus is an important cause of frailty and sarcopenia in the elderly population. However, at present, the scholars have not paid enough attention to the skeletal muscle weakness caused by the novel coronavirus. Therefore, this paper focuses on the long-novel coronavirus syndrome and sarcopenia to explore the pathological mechanism of skeletal muscle attenuation caused by the SARS-CoV-2 mediated "cytokine storm", mitochondrial damage, hypoxia state and other links,so as to raise the attention of clinical and academic researchers and improve the clinical strategy of frailty and sarcopenia after novel coronavirus infection.

Frailty and behavioral and psychological symptoms of dementia: a single center study

AbstractBackgrounddementia is a clinical syndrome characterized by progressive cognitive decline and loss of independence in activities of daily living. Alongside the cognitive symptoms, Behavioral and Psychological Symptoms of Dementia (BPSD) may arise, causing considerable distress to both patients and caregiversMethodaim of this retrospective study was to evaluate the correlation between frailty and BPSD in a population of older patients with dementia. BPSD were classified in three clusters: “mood/apathy”, “psychosis” and “hyperactivity”. Using the Clinical Frailty Scale (CFS), patients were categorized as “severely frail”, “mild/moderately frail” and “robust” (CFS ≥ 7, 4‐6 and ≤ 3, respectively). In order to better understand the complex pattern of relationships between the different factors, we performed a network analysis.Result209 patients (71.3% women, mean age 83.24±4.98 years) with a clinical diagnosis of dementia were enrolled. The most represented group was the mild/moderately frail one (n = 155, 74%); lower numbers were seen in the robust (n = 18, 9%) and severely frail (n = 36, 17%) ones. Among the “severely frail” the percentage of BPSD was higher compared to the “mild/moderate” and “robust” groups. A significant correlation between frailty and “hyperactivity” cluster emerged, both at baseline and follow up visits (p<0.001, p = 0.022, p = 0.028 respectively). At the network analysis, the degree of frailty related to behavioral and psychological symptoms of the hyperactivity cluster, such as agitation and motor aberrant activity; the relationship was still positive although not so strong with other symptoms like apathy and hallucinations.Conclusionin this study an association between frailty and the number of neuropsychiatric symptoms of the “hyperactivity” cluster was found; however, whether the loss of independence is a possible cause of frailty or viceversa is still to be determined. The assessment of frailty may help identifying patients at risk of developing behavioral and psychological symptoms of dementia, and could provide the clinicians with a time‐window to target intervention in the earliest phases of both frail condition and BPSD.

A combination of metformin and galantamine exhibits synergistic benefits in the treatment of sarcopenia.

Age-associated sarcopenia, characterized by a progressive loss in muscle mass and strength, is the largest cause of frailty and disability in the elderly worldwide. Current treatments involve nonpharmacological guidelines that few subjects can abide by, highlighting the need for effective drugs. Preclinical models were employed to test the benefits of RJx-01, a combination drug composed of metformin and galantamine, on sarcopenia. In worms, RJx-01 treatment improved lifespan, locomotion, pharyngeal pumping, and muscle fiber organization. The synergistic effects of RJx-01 were recapitulated in a transgenic mouse model that displays an exacerbated aging phenotype (Opa1-/-). In these mice, RJx-01 ameliorated physical performance, muscle mass and force, neuromuscular junction stability, and systemic inflammation. RJx-01 also improved physical performance and muscle strength in 22-month-old WT mice and also improved skeletal muscle ultrastructure, mitochondrial morphology, autophagy, lysosomal function, and satellite cell content. Denervation and myofiber damage were decreased in RJx-01-treated animals compared with controls. RJx-01 improved muscle quality rather than quantity, indicating that the improvement in quality underlies the beneficial effects of the combination drug. The studies herein indicate synergistic beneficial effects of RJx-01 in the treatment of sarcopenia and support the pursuit of RJx-01 in a human clinical trial as a therapeutic intervention for sarcopenia.

The sublingual microcirculation and frailty index in chronic kidney disease patients.

To examine the relationship between sublingual microcirculatory measures and frailty index in those attending a kidney transplant assessment clinic. Patients recruited had their sublingual microcirculation taken using sidestream dark field videomicroscopy (MicroScan, Micro Vision Medical, Amsterdam, the Netherlands) and their frailty index score using a validated short form via interview. A total of 44 patients were recruited with two being excluded due to microcirculatory image quality scores exceeding 10. The frailty index score indicated significant correlations with total vessel density (p < .0001, r = -.56), microvascular flow index (p = .004, r = -.43), portion of perfused vessels (p = .0004, r = -.52), heterogeneity index (p = .015, r = .32), and perfused vessel density (p < .0001, r = -.66). No correlation was shown between the frailty index and age (p = .08, r = .27). There is a relationship between the frailty index and microcirculatory health in those attending a kidney transplant assessment clinic, that is not confounded by age. These findings suggest that the impaired microcirculation may be an underlying cause of frailty.

Early changes in elderly food habits related to reduced protein intake

Age-related loss of muscle mass and function is a leading cause of frailty in elderly people. Changes in adult lifestyle (diet and physical activity) are highlighted as some causes and modifiable factors that can be challenged. The objective of this work was to analyze the changes in food-related habits that occur during the early stages of aging, focusing on those related to protein intake, and the reasons behind these changes. The study was carried out in Spain. Four discussion groups were held with 60–75 years old participants, to generate the list of changes in food-related habits and products consumed. These changes among the young elderly population were quantified through a questionnaire completed by 346 participants (65–75 years old, 50 % women). Factor analysis revealed seven dimensions of change in food habits: 1) eating healthier, 2) more time cooking and eating lunch at home, 3) buying/eating gourmet or indulgent products, 4) reducing the amount of food and having light meals, 5) shopping online, 6) shopping more frequently and in small stores, and 7) quick/easy to prepare dinners. Concerning changes in products consumed, three groups were observed: 1) group with no changes (23 %), 2) reduced certain protein foods (mainly meat and sausages) (37 %), and 3) also reduced the meat, sausages, and dairy desserts but increased others (fish, chicken, dairy products, and pulses) (40 %). The search for health was the main reason for avoiding certain foods, reducing the amount and portions, and for reducing the consumption of protein food products.

Accelerated aging in people experiencing homelessness: A rapid review of frailty prevalence and determinants.

Older people experiencing homelessness (PEH) are a rapidly growing population at risk of accelerated aging and the early onset of geriatric conditions. One construct that shows promise in predicting age-related decline is frailty. Better understanding the rates and causes of frailty in PEH may improve understanding of its antecedents, thereby facilitating more targeted health and aged care service interventions. The aim of this study was to conduct a rapid review on the prevalence and determinants of frailty in adult PEH. We conducted a rapid review of primary research papers studying PEH and frailty or frailty-related concepts. Fourteen studies were included, which indicate that frailty presents earlier and at higher rates in PEH than community-dwelling cohorts. A notable difficulty for many aging PEH was early-onset cognitive impairment which was associated with a range of negative functional outcomes. Another recurrent theme was the negative impact that drug and alcohol use and dependence can have on the health of PEH. Further, psychosocial and structural determinants such as loneliness, living in an impoverished neighborhood and being female had statistically significant associations with frailty and functional decline in PEH. PEH in their 40s and 50s can be frail and experience geriatric conditions, including cognitive impairment. Factors that have important relationships to frailty and functional decline in PEH include cognitive deficits, drug and alcohol dependence and loneliness, as well as upstream determinants such as gender and ethnicity. More targeted data and research on these factors, including cohort studies to better investigate their potentially causal effects, is important for researchers and practitioners assessing and treating frailty in PEH, particularly those interested in early intervention and prevention. CRD42022292549.

Subphenotypes of frailty in lung transplant candidates

Heterogeneous frailty pathobiology might explain the inconsistent associations observed between frailty and lung transplant outcomes. A Subphenotype analysis could refine frailty measurement. In a 3-center pilot cohort study, we measured frailty by the Short Physical Performance Battery, body composition, and serum biomarkers reflecting causes of frailty. We applied latent class modeling for these baseline data. Next, we tested class construct validity with disability, waitlist delisting/death, and early postoperative complications. Among 422 lung transplant candidates, 2 class model fit the best (P = .01). Compared with Subphenotype 1 (n = 333), Subphenotype 2 (n = 89) was characterized by systemic and innate inflammation (higher IL-6, CRP, PTX3, TNF-R1, and IL-1RA); mitochondrial stress (higher GDF-15 and FGF-21); sarcopenia; malnutrition; and lower hemoglobin and walk distance. Subphenotype 2 had a worse disability and higher risk of waitlist delisting or death (hazards ratio: 4.0; 95% confidence interval: 1.8-9.1). Of the total cohort, 257 underwent transplant (Subphenotype 1: 196; Subphenotype 2: 61). Subphenotype 2 had a higher need for take back to the operating room (48% vs 28%; P = .005) and longer posttransplant hospital length of stay (21 days [interquartile range: 14-33] vs 18 days [14-28]; P = .04). Subphenotype 2 trended toward fewer ventilator-free days, needing more postoperative extracorporeal membrane oxygenation and dialysis, and higher need for discharge to rehabilitation facilities (P ≤ .20). In this early phase study, we identified biological frailty Subphenotypes in lung transplant candidates. A hyperinflammatory, sarcopenic Subphenotype seems to be associated with worse clinical outcomes.

Functional Dentition, Chronic Periodontal Disease and Frailty in Older Adults—A Narrative Review

The likelihood of experiencing the impact of chronic disease rises with age, and cumulative functional deficits over time increase the risk of frailty in older adults. The exact causes of frailty are not clear, and research is needed to identify appropriate intervention measures to reduce risk of developing frailty in old age. To review the evidence on the relationship between frailty, dental status and chronic periodontitis and to determine if improvements in oral health of older adults can contribute to reversal of frailty. The oral cavity is the entry point to the gastro-intestinal tract, and natural teeth facilitate efficient mastication of food prior to swallowing and subsequent digestion. The loss of natural teeth, which is gradual and cumulative over the life course, is associated with diminished nutritional intake, especially in older adults. Furthermore, chronic periodontitis has been postulated as a risk factor for frailty. The evidence supporting a strong relationship between oral health status and frailty is not clearcut. Cross sectional studies suggest an association with missing teeth and chronic periodontal inflammation. However, there are very few longitudinal studies and accordingly, it is not currently possible to claim a causal relationship. As yet, there is no evidence to suggest that improvements in oral health contribute to reversal of frailty. Longitudinal studies with robust designs are required to better inform the relationship across functional dentition, chronic periodontitis and frailty in older adults.

Discrimination between possible sarcopenia and metabolic syndrome using the arterial pulse spectrum and machine-learning analysis

Sarcopenia is defined as decreased skeletal muscle mass and function, and is an important cause of frailty in the elderly, also being associated with vascular lesions and poor microcirculation. The present study aimed to combine noninvasive pulse measurements, frequency-domain analysis, and machine learning (ML) analysis (1) to determine the effects on the pulse waveform induced by sarcopenia and (2) to develop discriminating models for patients with possible sarcopenia. Radial blood pressure waveform (BPW) signals were measured noninvasively for 1 min in 133 subjects who visited Tri-Service General Hospital for geriatric health checkups. They were assigned to a robust group and a possible-sarcopenia group that combined dynapenia, presarcopenia, and sarcopenia. Two classification methods were used: ML analysis and a self-developed scoring system that used 40 harmonic pulse indices as features: amplitude proportions and their coefficients of variation, and phase angles and their standard deviations. Significant differences were found in several spectral indices of the BPW between possible-sarcopenia and robust subjects. Threefold cross-validation results indicated excellent discrimination performance, with AUC equaling 0.77 when using LDA and 0.83 when using our scoring system. The present noninvasive and easy-to-use measurement and analysis method for detecting sarcopenia-induced changes in the arterial pulse transmission condition could aid the discrimination of possible sarcopenia.

Associations of Nutrition-Related, Physical, and Social Factors and Their Combinations with Sarcopenia in Community-Dwelling Older Adults: Kashiwa Cohort Study.

Background: Sarcopenia is a major cause of frailty, which relates to nutrition-related, physical, and social factors. In this study, we aimed to discuss the cross-sectional association of sarcopenia with the above three factors both individually and comprehensively. Methods: Overall, 1257 older adults (≥65 years old) participated in this study. Sarcopenia was determined via the Asian Working Group for Sarcopenia 2019 criteria. The independent variables for nutrition-related, physical, and social factors and especially their criteria for health condition were defined separately. Binomial logistic regression analysis was carried out to testify the associations of sarcopenia with three factors individually and in combination. Results: The mean age was 74.6 (±5.5), and women were 47.7%. Sarcopenia prevalence was 7.5%. Participants who did not meet the criteria of nutritional health, physical fitness, or social robustness independently had significant associations with a higher adjusted odds ratio (aOR) of sarcopenia or its indices of lower grip strength, muscle mass, or gait speed. In comparison to participants meeting three criteria, those who met two, one, or none showed (marginally) significant association with increased aOR for sarcopenia (aOR (95% confidence interval)): two: 1.97 (0.84–4.64); one: 2.35 (1.00–5.23); none: 5.52 (2.30–13.23). Conclusions: Comprehensive countermeasures with the above three factors are indispensable for sarcopenia prevention.

Use of Dual-Energy X-ray Absorptiometry for Body Composition in Chronic Disease Management

Aging and chronic disease are often accompanied by changes in body composition that lead to decreased muscle mass and increased fat mass, even in weight-stable individuals. Both obesity and sarcopenia are important causes of frailty, disability, morbidity, and mortality. Diminished skeletal muscle and expanded visceral fat can act synergistically, which might maximize their effects on physical impairments and metabolic disorders. Dual-energy X-ray absorptiometry (DEXA) was regarded as one of the most versatile imaging techniques for evaluation of sarcopenia and obesity as well as osteoporosis. Whole-body DEXA allows total and regional assessment of the three compartments for fat mass, non-bone lean mass, and bone mineral content. Moreover, DEXA is accurate, reproducible, fast, relatively inexpensive, and involves very low radiation dose to the patient. Developments in DEXA equipment and software allow an accurate and differential estimate of visceral adipose tissue. This review summarizes the clinical practical application of whole-body DEXA values, with use of muscle and fat mass indices in the diagnostic workup of low muscle mass, sarcopenia, and sarcopenic obesity according to the most recent studies and guidelines.

Adipose-derived exosomes block muscular stem cell proliferation in aged mouse by delivering miRNA Let-7d-3p that targets transcription factor HMGA2

Sarcopenia is an aging-associated attenuation of muscular volume and strength and is the major cause of frailty and falls in elderly individuals. The number of individuals with sarcopenia is rapidly increasing worldwide; however, little is known about the underlying mechanisms of the disease. Sarcopenia often copresents with obesity, and some patients with sarcopenia exhibit accumulation of peri-organ or intra-organ adipose tissue as ectopic fat deposition, including atrophied skeletal muscle. In this study, we showed that transplantation of the perimuscular adipose tissue (PMAT) to the hindlimb thigh muscles of young mice decreased the number of integrin α7/CD29-double positive muscular stem/progenitor cells and that the reaction was mediated by PMAT-derived exosomes. We also found that the inhibition of cell proliferation was induced by Let-7d-3p miRNA that targets HMGA2, which is an important transcription factor for stem cell self-renewal, in muscular stem/progenitor cells and the composite molecular reaction in aged adipocytes. Reduction of Let-7 miRNA repressor Lin28 A/B and activation of nuclear factor-kappa B signaling can lead to the accumulation of Let-7d-3p in the exosomes of aged PMAT. These findings suggest a novel crosstalk between adipose tissue and skeletal muscle in the development of aging-associated muscular atrophy and indicate that adipose tissue–derived miRNAs may play a key role in sarcopenia.

Biomarkers of Age-Related Frailty and Frailty Related to Diseases: An Exploratory, Cross-Sectional Analysis from the MAPT Study

BackgroundFrailty may in most cases result from two main causes: the aging process (age-related frailty) and diseases (evolving chronic conditions or acute medical illnesses — disease-related frailty). The biological determinants characterizing these two main causes of frailty may be different.ObjectivesThe aim of this study is to compare the biological and neuroimaging profile of people without frailty, those with age-related frailty, and subjects with disease-related frailty in community-dwelling older adults.Material and MethodsWe performed a secondary, cross-sectional analysis from the Multidomain Alzheimer Preventive Trial (MAPT). We included 1199 subjects without frailty throughout the 5-year follow-up, 82 subjects with incident age-related frailty, and 53 with incident disease-related frailty. Available blood biomarkers involved nutritional (eg, vitamin D, omega-3 fatty acids), inflammatory-related (IL-6, TNFR1, GDF15), neurodegenerative (eg, beta-amyloid, neurofilament light chain) and neuroimaging markers (MRI, Amyloid-PET).ResultsAlthough not statistically significant, the results of the unadjusted model showed increasing gradients for inflammatory markers (GDF15, TNFR1) and decreasing gradients for nutritional and neuroimaging markers (omega 3 index, hippocampal volume) from age-related frailty participants to individuals with disease-related frailty. Considering the linear models we observed higher GDF15 values in disease-related frailty group compared to age-related frailty individuals [β = 242.8 (49.5, 436.2)]. We did not find any significant difference between subjects without frailty and those with age-related frailty. Subjects with disease-related frailty compared to subjects without frailty had lower values of DHA [β = −2.42 (−4.76, −0.08)], Omega 3 Index [β = −0.50 (−0.95, −0.06)] and hippocampal volume [β = −0.22 (−0.42,−0.02)]. They also had higher values of GDF15 [β = 246.1 (88.9, 403.4)] and TNFR1 [β = 157.5 (7.8, 307.2)].ConclusionAge-related frailty and disease-related frailty may represent different degrees of frailty severity on a biological level. Further research is needed to identify biomarkers potentially able to distinguish these classifications of frailty.

Molecular Phenotypes of Frailty in Lung Transplant Candidates

<h3>Purpose</h3> The potential for heterogenous pathobiology underlying physical frailty might explain the inconsistent associations observed between frailty and poor outcomes in lung transplantation. We hypothesize that molecular phenotyping could refine frailty measurement and ultimately tailor interventions. <h3>Methods</h3> In a three-center cohort of lung transplant candidates, we measured frailty by the Short Physical Performance Battery (SPPB); demographic and clinical variables; body composition by bioelectrical impedance, and 17 serum biomarkers reflecting commonly cited causes of frailty including inflammation, sarcopenia, adiposity, mitochondrial and neurohormonal dysfunction. Among those pre-frail or frail (SPPB <12), we first applied latent class modelling to the baseline data and then followed participants forward in time. The best-fitting model was determined by the Bayesian Information Criteria and the Vuong-Lo-Mendell-Rubin test. We tested predictive validity of these classes with disability by the Lung Transplant Valued Life Activities scale and by candidate delisting for becoming too ill or death. <h3>Results</h3> In 442 participants, a 3 latent class model best fit (p = 0.046; Figure 1A). Type A was characterized by higher serum biomarkers of inflammation and sarcopenia (lower muscle mass [ASMI] and grip strength); Type B by sarcopenia, high adiposity (VFA), and lack of inflammation, and Type C was relatively fit (higher ASMI and grip strength) and without inflammation (Figure 1B). Amongst the Type A endotype, 13% of participants died or were delisted compared to 6% in both Type B and C (p = 0.15). Participants comprising Type A reported worse disability (LT-VLA 1.7) than Types B and C (1.4 and 1.3, respectively) (p < 0.001) and had shorter time to delisting or death (1.4 vs 8.0 and 4.0 months, respectively) (p < 0.001). <h3>Conclusion</h3> We identified distinct biological phenotypes of frailty. A frailty phenotype characterized by systemic inflammation and sarcopenia appears to be associated with worse clinical outcomes.

Guava Fruit and Acacia pennata Vegetable Intake Association with Frailty of Older Adults in Northern Thailand.

As Thailand moves toward an aging society, frailty has become a concern amongst northern Thai elderly. The causes of frailty are multifactorial and include genetic, environmental, and socio-economic factors; diet is of particular interest. A cross-sectional study was conducted from September to October 2017 to investigate what kind of diets normally consumed by 350 Thai elders were associated with frailty using a questionnaire and frailty determination by Fried’s phenotype followed by phytochemical analyses of the diets. The multivariable logistic regression analysis demonstrated a significant positive association between certain foods and lower frailty. Guava fruit and Acacia pennata vegetable consumption had lower odds of frailty, which were 0.52 times (95% CI 0.28–0.96, p = 0.037) and 0.42 times (95% CI 0.21–0.83, p = 0.012) when adjusted for the potential confounders. The phytochemical analyses of guava fruit showed a significantly higher amount of total flavonoids (p < 0.001), total phenolic compounds (p = 0.002), and antioxidant capacity, including DPPH (p < 0.001), ABTS (p < 0.001), and FRAP (p = 0.002) when compared to those of banana. Acacia pennata vegetable contained a significantly higher amount of total phenolic compounds (p = 0.012) when compared to those of lettuce. These findings may assist in health promotion programs of frailty prevention by encouraging an increase in consumption of either guava fruit or Acacia pennata vegetable among Thai elderly.

The Interactome in the Evolution From Frailty to Sarcopenic Dependence.

Biomarkers are essential tools for accurate diagnosis and effective prevention, but their validation is a pending challenge that limits their usefulness, even more so with constructs as complex as frailty. Sarcopenia shares multiple mechanisms with frailty which makes it a strong candidate to provide robust frailty biomarkers. Based on this premise, we studied the temporal evolution of cellular interactome in frailty, from independent patients to dependent ones. Overweight is a recognized cause of frailty in aging, so we studied the altered mechanisms in overweight independent elderly and evaluated their aggravation in dependent elderly. This evidence of the evolution of previously altered mechanisms would significantly support their role as real biomarkers of frailty. The results showed a preponderant role of autophagy in interactome control at both different functional points, modulating other essential mechanisms in the cell, such as mitochondrial capacity or oxidative stress. Thus, the overweight provoked in the muscle of the elderly an overload of autophagy that kept cell survival in apparently healthy individuals. This excessive and permanent autophagic effort did not seem to be able to be maintained over time. Indeed, in dependent elderly, the muscle showed a total autophagic inactivity, with devastating effects on the survival of the cell, which showed clear signs of apoptosis, and reduced functional capacity. The frail elderly are in a situation of weakness that is a precursor of dependence that can still be prevented if detection is early. Hence biomarkers are essential in this context.

The Role of Machine Learning in Diagnosing Bipolar Disorder: Scoping Review.

BackgroundBipolar disorder (BD) is the 10th most common cause of frailty in young individuals and has triggered morbidity and mortality worldwide. Patients with BD have a life expectancy 9 to 17 years lower than that of normal people. BD is a predominant mental disorder, but it can be misdiagnosed as depressive disorder, which leads to difficulties in treating affected patients. Approximately 60% of patients with BD are treated for depression. However, machine learning provides advanced skills and techniques for better diagnosis of BD.ObjectiveThis review aims to explore the machine learning algorithms used for the detection and diagnosis of bipolar disorder and its subtypes.MethodsThe study protocol adopted the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. We explored 3 databases, namely Google Scholar, ScienceDirect, and PubMed. To enhance the search, we performed backward screening of all the references of the included studies. Based on the predefined selection criteria, 2 levels of screening were performed: title and abstract review, and full review of the articles that met the inclusion criteria. Data extraction was performed independently by all investigators. To synthesize the extracted data, a narrative synthesis approach was followed.ResultsWe retrieved 573 potential articles were from the 3 databases. After preprocessing and screening, only 33 articles that met our inclusion criteria were identified. The most commonly used data belonged to the clinical category (19, 58%). We identified different machine learning models used in the selected studies, including classification models (18, 55%), regression models (5, 16%), model-based clustering methods (2, 6%), natural language processing (1, 3%), clustering algorithms (1, 3%), and deep learning–based models (3, 9%). Magnetic resonance imaging data were most commonly used for classifying bipolar patients compared to other groups (11, 34%), whereas microarray expression data sets and genomic data were the least commonly used. The maximum ratio of accuracy was 98%, whereas the minimum accuracy range was 64%.ConclusionsThis scoping review provides an overview of recent studies based on machine learning models used to diagnose patients with BD regardless of their demographics or if they were compared to patients with psychiatric diagnoses. Further research can be conducted to provide clinical decision support in the health industry.

Abstract 11825: The Association Between Frailty and Vascular Endothelial Growth Factor Families in Patients With Heart Failure: The PREHOSP-CHF Study

Background: Frailty is a complex clinical syndrome associated with ageing and chronic illness, and is common in heart failure (HF). Vascular endothelial dysfunction including maladaptive angiogenesis and lymphangiogenesis is involved in the pathogenesis of HF, and is also considered to be the causes of frailty. We investigated the association of vascular endothelial growth factor (VEGF) families, central regulators of angiogenesis and lymphangiogenesis, with frailty, and prognostic role of these cytokines in frail HF patients. Methods: We performed a multicenter prospective cohort study to determine the predictive value of VEGF families for prognosis among patients with HF. A total of 1,024 patients (mean age, 75.5 years, 58.7% male) were included in the analyses. Serum levels of VEGF, VEGF-C, VEGF-D, and soluble VEGF receptor-2 (sVEGFR-2) were measured. Frailty was assessed by Canadian Study of Health and Aging Clinical Frailty Scale (CFS). Results: A total of 256 (25.1%) patients had frailty (CFS≥5) at baseline. Frail patients were older, more likely female, and had lower body mass index, higher NYHA class, and higher rates of prior hospitalization for HF, HF with preserved ejection fraction, anemia, cerebrovascular disease, and dementia. N-terminal pro brain natriuretic peptide, high sensitivity troponin I, and high sensitivity C-reactive protein levels were higher in frail patients. During the 2-year follow-up, 211 all cause death occurred. In Kaplan-Maier analysis, frail patients showed significantly higher incidence of all-cause (hazard ratio [HR], 4.12; 95% confidence interval [CI], 3.14-5.42). Regarding VEGF families, frail patients had significantly lower levels of sVEGFR-2 and VEGF-C, and higher levels of VEGF-D. Multiple regression analysis revealed that VEGF-C had inverse correlation with CFS (P, 0.03). After adjusting for clinical confounders, a low VEGF-C level was independently associated with all-cause death in frail patients (HR, 0.74; 95%CI, 0.58-0.94 for 1-SD increase), but was not in non-frail patients (HR, 0.87; 95%CI, 0.64-1.14 for 1-SD increase) (P for interaction, 0.09). Conclusions: In HF patients, a low VEGF-C value was associated with frailty and was independent risk for all-cause death in frail patients.