scholarly journals Frailty Is Associated With Neutrophil Dysfunction Which Is Correctable With Phosphoinositol-3-Kinase Inhibitors

2020 ◽  
Vol 75 (12) ◽  
pp. 2320-2325
Author(s):  
Daisy Wilson ◽  
William Drew ◽  
Alice Jasper ◽  
Helena Crisford ◽  
Peter Nightingale ◽  
...  

Abstract Neutrophil dysfunction has been described with age, appears exaggerated in infection, with altered phosphoinositol signaling a potential mechanism. However, functional aging is heterogeneous. Frailty is a negative health status and is more common in older adults. We hypothesized that neutrophil migration may be compromised in frailty, associated with the degree of frailty experienced by the older person. We compared measures of frailty, neutrophil function, and systemic inflammation in 40 young and 77 older community-dwelling adults in the United Kingdom. Systemic neutrophils exhibited an age-associated reduction in the accuracy of migration (chemotaxis) which was further blunted with frailty. The degree of migratory inaccuracy correlated with physical (adjusted hand grip strength) and cognitive (Stroop test) markers of frailty. Regression analysis demonstrated that age, Charlson comorbidity index, and frailty index were able to predict neutrophil chemotaxis. Reduced chemotaxis of neutrophils from frail adults could be reversed using selective PI3K inhibitors. Exposure of neutrophils from young adults to plasma from chronically inflamed frail older adults could not recapitulate the migratory deficit in vitro, and there were no relationships with systemic inflammation and neutrophil dysfunction. Frailty exaggerated the neutrophil deficits seen with advanced age but aspects of the frailty-associated deficit in neutrophil function are rescuable and thus potentially form a therapeutic target to improve outcomes from infection in older adults.

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 269-269
Author(s):  
Kenneth Madden ◽  
Boris Feldman ◽  
Shane Arishenkoff ◽  
Graydon Meneilly

Abstract The age-associated loss of muscle mass and strength in older adults is called sarcopenia, and it is associated with increased rates of falls, fractures, hospitalizations and death. Sarcopenia is one of the most common physical etiologies for increased frailty in older adults, and some recent work has suggested the use of Point-of care ultrasound (PoCUS) measures as a potential measure of muscle mass. The objective of this study was to examine the association of PoCUS measures of muscle thickness (MT) with measures of frailty in community-dwelling older adults. We recruited 150 older adults (age >= 65; mean age 80.0±0.5 years, 66 women, 84 men) sequentially from 5 geriatric medicine clinics (Vancouver General Hospital). We measured lean muscle mass (LMM, by bioimpedance assay) and an ultrasonic measure of muscle quantity (MT, vastus medialis muscle thickness) in all subjects, as well as two outcome measures of frailty (FFI, Fried Frailty Index; RCFS, Rockwood Clinical Frailty Scale). In our models, MT showed an inverse correlation with the FFI (Standardized β=-0.2320±0.107, p=0.032) but no significant correlation with the RCFS (Standardized β = -0.025±0.086, p=0.776). LMM showed no significant association with either FFI (Standardized β=-0.232±0.120, p=0.055) or RCFS (Standardized β = -0.043±0.119, p=0.719). Our findings indicate that PoCUS measures show potential as a way to screen for physical manifestations of frailty and might be superior to other bedside methods such as bioimpedance assay. However, PoCUS measures of muscle thickness will likely miss patients showing frailty in the much broader context captured by the RCFS.


2019 ◽  
Vol 48 (Supplement_4) ◽  
pp. iv9-iv12
Author(s):  
Resshaya Roobini Murukesu ◽  
Devinder Kaur Ajit Singh ◽  
Noor Izyani Mokhtar ◽  
Janet Bong May Ing ◽  
Ponnusamy Subramaniam ◽  
...  

Abstract Introduction The presence of either frailty or cognitive impairment have been determined as precursors of falls among older adults. However, the association between falls and cognitive frailty has yet to be established. Objective To investigate the association between falls and cognitive frailty among community dwelling older adults. Methods A total of 246 Malaysian community dwelling older adults aged 60 years and above residing in the state of Selangor participated in this cross-sectional study. Sociodemographic details and clinical characteristics including the history of falls were obtained via interview. The presence of cognitive frailty was identified using the Clinical Dementia Rating Scale and Fried Frailty Index. Data analysis was carried out via binary logistic regression. Results The prevalence of falls and cognitive frailty in this study were 21.2% and 21.9% respectively among community dwelling older adults (mean age 72.39±5.40). No significant relationship between falls and cognitive frailty [OR:1.187, 95% C.I: 0.493-2.856, p=0.702] was demonstrated. However, older women [OR:2.663, 95% C.I, 1.136-6.239, p=0.024] and the presence of multi-morbidities [OR: 1.431, 95% C.I, 1.026-1.997, p=0.035] were significantly associated with falls which corroborates with existing literature. Conclusion Cognitive frailty was not a significant risk factor of falls among community dwelling older adults in this study. Further research is required in prospective, longitudinal, population-based studies to confirm this result.


CJEM ◽  
2019 ◽  
Vol 21 (S1) ◽  
pp. S11 ◽  
Author(s):  
E. Mercier ◽  
A. Jones ◽  
A. Brousseau ◽  
J. Hirdes ◽  
F. Mowbray ◽  
...  

Introduction: Elder abuse is infrequently detected in the emergency department (ED) and less than 2% are reported to proper law authorities by ED physicians. This study aims to examine the characteristics of community-dwelling older adults who screened positive for elder abuse during home care assessments and the epidemiology of ED visits by these patients relative to other home care patients. Methods: This study utilized a population-based retrospective cohort study of home care patients in Canada between April 1, 2007 and March 31, 2015. Standardized, comprehensive home care assessments were extracted from the Home Care Reporting System. A positive screen for elder abuse was defined as at least one these criteria: fearful of a caregiver; unusually poor hygiene; unexplained injuries; or neglected, abused, or mistreated. Home care assessments were linked to the National Ambulatory Care Reporting System in the regions and time periods in which population-based estimates could be obtained to identify all ED visits within 6 months of the home care assessment. Results: A total of 30,413 from the 2,401,492 patients (1.3%) screened positive for elder abuse during a home care assessment. They were more likely to be male (40.5% versus 35.3%, p < 0.001), to have a cognitive impairment (82.9% versus 65.3%, p < 0.001), a higher frailty index (0.27 versus 0.22, p < 0.001) and to exhibit more depressive symptoms (depression rating scale 1 or more: 68.7% versus 42.7%, p < 0.001). Patient who screened positive for elder abuse were less likely to be independent in activities of daily living (41.9% versus 52.7%, p < 0.001) and reported having fallen more frequently (44.2% versus 35.5%, p < 0.001). Caregiver expressing distress was associated with elder abuse (35.3% versus 18.3%, p < 0.001) but not a higher number of hours caring for the patient. Victims of elder abuse were more likely to attend the ED for low acuity conditions (Canadian triage and acuity scale (CTAS) 4 or 5). Diagnosis at discharge from ED were similar with the exception of acute intoxication that was more frequent in patients who are victims of abuse. Conclusion: Elder abuse is infrequently detected during home care assessments in community-dwelling older adults. Higher frailty index, cognitive impairment, depressive symptoms were associated with elder abuse during homecare assessments. Patients who are victims of elder abuse are attending EDs more frequently for low acuity conditions but ED diagnosis at discharge, except for acute intoxication, are similar.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Douglas Salguero ◽  
Juliana Ferri-Guerra ◽  
Nadeem Y. Mohammed ◽  
Dhanya Baskaran ◽  
Raquel Aparicio-Ugarriza ◽  
...  

Abstract Background Frailty is defined as a state of vulnerability to stressors that is associated with higher morbidity, mortality and healthcare utilization in older adults. Ageism is “a process of systematic stereotyping and discrimination against people because they are old.” Explicit biases involve deliberate or conscious controls, while implicit bias involve unconscious processes. Multiple studies show that self-directed ageism is a risk factor for increased morbidity and mortality. The purpose of this study was to determine whether explicit ageist attitudes are associated with frailty in Veterans. Methods This is a cross-sectional study of Veterans 50 years and older who completed the Kogan’s Attitudes towards Older People Scale (KAOP) scale to assess explicit ageist attitudes and the Implicit Association Test (IAT) to evaluate implicit ageist attitudes from July 2014 through April 2015. We constructed a frailty index (FI) of 44 variables (demographics, comorbidities, number of medications, laboratory tests, and activities of daily living) that was retrospectively applied to the time of completion of the KAOP and IAT. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multinomial logistic regression models with frailty status (robust, prefrail and frail) as the outcome variable, and with KAOP and IAT scores as the independent variables. Age, race, ethnicity, median household income and comorbidities were considered as covariates. Results Patients were 89.76% male, 48.03% White, 87.93% non-Hispanic and the mean age was 60.51 (SD = 7.16) years. The proportion of robust, pre-frail and frail patients was 11.02% (n = 42), 59.58% (n = 227) and 29.40% (n = 112) respectively. The KAOP was completed by 381 and the IAT by 339 participants. In multinomial logistic regression, neither explicit ageist attitudes (KAOP scale score) nor implicit ageist attitudes (IAT) were associated with frailty in community dwelling Veterans after adjusting for covariates: OR = .98 (95% CI = .95–1.01), p = .221, and OR:=.97 (95% CI = .37–2.53), p = .950 respectively. Conclusions This study shows that neither explicit nor implicit ageist attitudes were associated with frailty in community dwelling Veterans. Further longitudinal and larger studies with more diverse samples and measured with other ageism scales should evaluate the independent contribution of ageist attitudes to frailty in older adults.


2020 ◽  
Vol 75 (6) ◽  
pp. 1143-1147 ◽  
Author(s):  
Il-Young Jang ◽  
Hee-Won Jung ◽  
Hea Yon Lee ◽  
Hyungchul Park ◽  
Eunju Lee ◽  
...  

Abstract Background To determine the clinically meaningful changes and responsiveness of widely used frailty measures. Methods We analyzed data from a prospective cohort study of 1,135 community-dwelling older adults who underwent assessments of frailty and health-related quality of life using the EuroQol-5D at baseline and 1 year later. Frailty measures included deficit-accumulation frailty index (FI); frailty phenotype; Fatigue, Resistance, Ambulation, Illness, and Loss of Weight scale; and the Study of Osteoporotic Fracture (SOF) index. We determined the clinically meaningful changes by the distribution-based method and the anchor-based method using the EuroQol-5D score and responsiveness indices. Results Frailty measures were available in 925 participants at 1 year (81.5%). Based on the distribution-based method, small and large clinically meaningful changes were 0.019 and 0.057 for FI, 0.249 and 0.623 for frailty phenotype, 0.235 and 0.587 for FRAIL scale, and 0.116 and 0.289 for SOF index, respectively. The anchor-based estimates of small and large changes were 0.028 and 0.076 for FI, 0.097 and 0.607 for frailty phenotype, 0.269 and 0.368 for FRAIL scale, and 0.023 and 0.287 for SOF index, respectively. Based on the responsiveness index, per-group sample sizes to achieve 80% power in clinical trials, ranged from 51 (FI) to 7,272 (SOF index) for a small change and 9 (FI) to 133 (FRAIL scale) for a large change. Conclusions The estimates of clinically meaningful change of frailty measures can inform the choice of frailty measures to track longitudinal changes of frailty in clinical trials and clinical care of community-dwelling older adults.


Author(s):  
Carl-Philipp Jansen ◽  
Nima Toosizadeh ◽  
M. Jane Mohler ◽  
Bijan Najafi ◽  
Christopher Wendel ◽  
...  

Abstract Background In older adults, the linkage between laboratory-assessed ‘motor capacity’ and ‘mobility performance’ during daily routine is controversial. Understanding factors moderating this relationship could help developing more valid assessment as well as intervention approaches. We investigated whether the association between capacity and performance becomes evident with transition into frailty, that is, whether frailty status moderates their association. Methods We conducted a cross-sectional analysis of the observational Arizona Frailty Cohort Study (ClinicalTrials.gov identifier: NCT01880229) in a community-dwelling cohort in Tucson, Arizona. Participants were N = 112 older adults aged 65 years or older who were categorized as non-frail (n = 40), pre-frail (n = 53) or frail (n = 19) based on the Fried frailty index. Motor capacity was quantified as normal (NWS) and fast walking speed (FWS). Mobility performance was quantified as 1) cumulated physical activity (PA) time and 2) everyday walking performance (average steps per walking bout; maximal number of steps in one walking bout), measured by a motion sensor over a 48 h period. Hierarchical linear regression analyses were performed to evaluate moderation effects. Results Unlike in non-frail persons, the relationship between motor capacity and mobility performance was evident in pre-frail and frail persons, confirming our hypothesis. A moderating effect of frailty status was found for 1) the relationship between both NWS and FWS and maximal number of steps in one bout and 2) NWS and the average steps per bout. No moderation was found for the association between NWS and FWS with cumulated PA. Conclusion In pre-frail and frail persons, motor capacity is associated with everyday walking performance, indicating that functional capacity seems to better represent mobility performance in this impaired population. The limited relationship found in non-frail persons suggests that other factors account for their mobility performance. Our findings may help to inform tailored assessment approaches and interventions taking into consideration a person’s frailty status.


Salmand ◽  
2019 ◽  
pp. 652-665
Author(s):  
Sima Ghasemi ◽  
Nastaran Keshavarz Mohammadi ◽  
Farahnaz Mohammadi Shahboulaghi ◽  
Ali Ramezankhani ◽  
Yadollah Mehrabi

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