Effects of Ninjin'yoeito on Patients with Chronic Obstructive Pulmonary Disease and Comorbid Frailty and Sarcopenia: A Preliminary Open-Label Randomized Controlled Trial.

Purpose: To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin'yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: Patients with COPD (GOLD II or higher) and fatigue were randomly assigned to Group A (n = 28; no medication for 12 weeks, followed by 12-week administration) or B (n= 25; 24-week continuous administration). Visual analog scale (VAS) symptoms of fatigue, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) Dyspnea Scale were examined. Physical indices such asknee extension leg strength and walking speed, skeletal muscle mass index (SMI), and respiratory function test were also measured. Results: VAS fatigue scales in Group B significantly improved after 4, 8, and 12 weeks compared to those in Group A (each p<0.001, respectively). Right and left knee extension leg strength in Group B significantly improved after 12 weeks compared to that in Group A (p=0.042 and p=0.037, respectively). The 1-s walking speed for continued to increase significantly over 24 weeks in Group B (p=0.016, p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001 after 4, 8, 12, 16, 20, and 24 weeks, respectively); it also significantly increased after the administration of Ninjin'yoeito in Group A. In Group B, the SMI significantly increased at 12 weeks in patients with sarcopenia (p=0.025). The CAT scores in Group B significantly improved after 12 weeks compared to those in Group A (p=0.006). The mMRC scores in Group B also significantly improved after 8 and 12 weeks compared to those in Group A (p= 0.045 and p <0.001, respectively). The changes in %FEV1.0 in Group B were significantly improved at 12 and 24 weeks (p=0.039 and p=0.036, respectively). Conclusion: Overall, Ninjin'yoeito significantly improved patients' quality of life, physical activity, muscle mass, and possibly lung function, suggesting that Ninjin'yoeito may improve frailty and sarcopenia in patients with COPD.

A simple scoring algorithm based on intrinsic capacity for functional ability in community-dwelling older adults in Taiwan.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of the overall well-being of older adults, and assessing of IC can help identify early stage of disability and tailor intervention to individual needs. However, there is a lack of effective and simple IC assessment tools. This study aimed to establish predictive scoring algorithms of IC to identify older adults at high risk of impaired functional ability. METHODS: We conducted a cross-sectional study in Southern Taiwan, measuring IC using 7 subitems: cognition, locomotion, vitality, vision, hearing, psychological well-being, and medication usage were measured. Functional ability outcomes included frailty, basic activities of daily living, and instrumental activities of daily living (IADL). The capability of 7 domains of IC in predicting functional ability was assessed by multivariable logistic regression. The prediction of capability of scoring algorithms was indicated by receiver operating characteristic (AUC) curves and measures of sensitivity and specificity. RESULTS: A total of 1,152 older adults were recruited and analyzed. Locomotion emerged as a significant predictor of IADL disability and worsening frailty. The IC-based weighted scoring algorism for predicting IADL demonstrated satisfactory capability (AUC: 0.80), as did the algorithm for predicting worsening frailty (AUC: 0.90). The optimal cutoff points for predicting IADL disability and frailty worse were estimated respectively at 13 and 16, with sensitivity/specificity values of 0.74/0.75 for the IADL prediction algorithm and 0.92/0.77 for the frailty prediction algorithm. CONCLUSION: Our 7-domain IC screening tool proves to be sensitive and practical for early identification of functional disability and frailty among community-dwelling older adults in Taiwan.

Predictors of Urinary and Fecal Incontinence in Prefrail and Frail Older Adults: A Cross-Sectional Study of the FRAGSALUD Project.

BACKGROUND: Frailty is associated with urinary and fecal incontinence, which are common geriatric syndromes. This study aims to identify health factors associated with incontinence in prefrail or frail older adults living in the community. METHODS: This multicenter cross-sectional study included 225 older adults (75.0 ±â€…6.4 years) with prefrailty or frailty based on the 5-component Fried phenotype. Physical function was assessed using the Short Physical Performance Battery (SPPB). Physical activity, inactivity, and sleep were estimated using a wrist-worn accelerometer. Urinary or fecal incontinence was registered using the Barthel scale (urine and bowel items). Multivariable logistic regression analyses, with age as a covariate, were conducted to identify associations of incontinence. RESULTS: In our participants, 27% presented urinary or fecal incontinence with no sex differences (p = .266). Our results showed that age, daily medication count, and number of falls in the previous year independently predicted incontinence in frail and prefrail older adults (p < .05). Some Fried's criteria, including self-reported exhaustion, gait speed, and handgrip strength, were associated with the presence of incontinence (p < .05), but not Fried's classification. The SPPB total score and its isolated variables were significantly associated with the urinary and fecal incontinence (p < .05). However, none of the accelerometer outcomes showed significant associations with incontinence status. CONCLUSIONS: According to this study, age, number of medications, and falls (but not sex) are linked to urinary and fecal incontinence in frail or prefrail older adults living in the community, recommending the assessment of physical function using the SPPB rather than estimating daily physical activity, inactivity, or sleep.

Systolic and diastolic blood pressure time in target range and cardiovascular outcomes in patients with hypertension and pre-frailty or frailty status.

In patients with hypertension and pre-frailty or frailty, the influence of systolic (SBP) and diastolic blood pressure (DBP) time in target range (TTR) on clinical outcomes is unclear. Thus, we conducted a post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). Classifying 4208 participants into frail and non-frail groups using a frailty index, the study calculated blood pressure time in target range (BP-TTR) for the first three months using the Rosendaal method. The primary endpoint included a composite of nonfatal myocardial infarction (MI), acute coronary syndromes, stroke, acute decompensated heart failure (ADHF), and cardiovascular death. Relationships between BP-TTR and outcomes were analyzed using Kaplan-Meier curves, Cox models, and restricted cubic spline curves, with subgroup analysis for further insights. In a median follow-up of 3.17 years, primary outcomes occurred in 6.7% of participants. Kaplan-Meier analysis showed that a lower systolic blood pressure time in target range (SBP-TTR) (0%-25%) correlated with an increased cumulative incidence of the primary outcome (p < .001), nonfatal MI (P = .021), stroke (P = .004), and cardiovascular death (P = .002). A higher SBP-TTR (75%-<100%) was linked to a reduced risk of these outcomes. The restricted cubic spline (RCS) curve revealed a linear association between SBP-TTR and the primary outcome (non-linear P = .704). Similar patterns were observed for diastolic blood pressure time in target range (DBP-TTR). Subgroup analysis showed that the protective effect of higher SBP-TTR was less pronounced at low DBP-TTR levels (P for interaction = .023). In conclusion, this study highlights the importance of maintaining BP within the target range to mitigate cardiovascular risks in this population.

Association Between Orthostatic Hypertension and Frailty Among Older Patients With Hypertension.

BACKGROUND: Frailty frequently coexists with hypertension in older patients. We aimed to evaluate the association between frailty and positional change in blood pressure, especially orthostatic hypertension. METHODS: Participants were recruited from 12 University hospitals in South Korea. Using a digital device, trained research nurses measured blood pressure in the supine and standing positions. Physical frailty was evaluated using the Korean version of the FRAIL questionnaire, gait speed, and handgrip strength. Orthostatic hypertension was defined as a ≥20-mm Hg increase in systolic blood pressure within 3 minutes of standing and upright systolic blood pressure of ≥140 mm Hg. RESULTS: We analyzed the data of 2065 participants who had been enrolled until December 31, 2022. The mean age was 73.2±5.6 years, and 52.0% were female. The mean blood pressure was 137.1±14.9/75.1±9.7 mm Hg. Among the participants, 1886 (91.3%) showed normal response after standing, but 94 (4.6%) had orthostatic hypertension, and 85 (4.1%) had orthostatic hypotension. Orthostatic hypertension was associated with female sex, obesity, cognitive function, physical frailty, and lower quality of life. In the multivariable analysis, body mass index and frailty status were independently associated with orthostatic hypertension. CONCLUSIONS: Orthostatic hypertension is associated with physical frailty, cognitive impairment, and low quality of life in older patients with hypertension. Therefore, evaluation of orthostatic blood pressure changes to confirm orthostatic hypertension or hypotension in frail older adults will serve as an important diagnostic procedure in vulnerable patients. Further studies are required to identify the underlying mechanisms of this association.

Protein intake and its relationship with frailty in chronic kidney disease.

INTRODUCTION: Patients with chronic kidney disease (CKD) are susceptible to frailty because of a range of nutrition-related factors. While protein restriction is commonly advised to preserve kidney function in patients with CKD, insufficient protein intake could potentially exacerbate frailty risk. This study aimed to elucidate the relationship between frailty and protein intake in patients with CKD. METHODS: This cross-sectional study enrolled patients with CKD stage 3-5. Frailty and prefrailty were assessed using the Japanese version of the Cardiovascular Health Study (J-CHS) criteria. To estimate dietary protein intake, Maroni's formula based on 24-h urine collection was used. The potential association between frailty/pre-frailty and protein intake was investigated using a logistic regression analysis. RESULTS: Ninety-seven individuals with CKD were included in the study, with a median age of 73.0 years (interquartile range: 67.0, 82.0). Among them, 34 were women (35.1%), and the estimated glomerular filtration rate (eGFR) was 36.3 mL/min/1.73 m2 (interquartile range: 26.9, 44.1). Frailty and pre-frailty were identified in 13.4% and 55.7% of participants, respectively. Comparing the groups, protein intake in the frailty/pre-frailty group (0.83 g/kgBW/day [0.72, 0.93]) was lower than that in the robust group (0.89 g/kgBW/day [0.84, 1.19], p = 0.002). Upon logistic regression analysis, protein intake exhibited an independent association with frailty/pre-frailty (odds ratio: 0.72, 95% confidence interval: 0.59-0.89, p = 0.003). CONCLUSION: Reduced protein intake in patients with CKD is associated with frailty and pre-frailty. It is advisable to ensure that patients with CKD who are at risk of frailty consume an adequate amount of protein.

Independent Association between Cognitive Frailty and Cardio-Ankle Vascular Index in Community-Dwelling Older Adults.

INTRODUCTION: Although arterial stiffness has been suggested to be associated with poor physical function and mild cognitive impairment (MCI), its association with cognitive frailty (CF), a comorbidity of both, is unclear. This study aims to examine the association between CF and arterial stiffness in community-dwelling older adults. METHODS: A cross-sectional analysis of 511 community-dwelling older adults aged 65 years or older (mean age 73.6 ± 6.2 years, 63.6% women), who participated in a community cohort study (Tarumizu Study, 2019), was conducted. Poor physical function was defined as either slowness (walking speed <1.0 m/s) or weakness (grip strength <28 kg for men and <18 kg for women). MCI was defined by the National Center for Geriatrics and Gerontology Functional Assessment Tool as a decline of at least 1.5 standard deviation from age- and education-adjusted baseline values in any one of the four cognitive domains (memory, attention, executive, and information processing). CF was defined as the combination of poor physical function and MCI. Arterial stiffness was measured using the Cardio-Ankle Vascular Index (CAVI), and the average of the left and right sides (mean CAVI) was used. RESULTS: Multinomial logistic regression analysis adjusted for covariates was performed with the four groups of robust, poor physical function, MCI, and CF as dependent variables and mean CAVI as an independent variable. Using the robust group as reference, the poor physical function and MCI groups showed no significant relationship with the mean CAVI. The mean CAVI was significantly higher in the CF group (odds ratio 1.62, 95% confidence interval: 1.14-2.29). CONCLUSION: A significant association was found between CF and the higher CAVI (progression of arterial stiffness). Careful observation and control of CAVI, which is also an indicator of arterial stiffness, may be a potential target for preventive interventions for CF.

Relação entre força de preensão manual, funcionalidade e fragilidade física em pessoas idosas: revisão integrativa / Relación entre fuerza de agarre manual, funcionalidad y fragilidad física en ancianos: una revisión integradora / Relationship between handgrip strength, functionality, and physical frailty in elderly people: an integrative review

RESUMO Objetivo: analisar as publicações científicas sobre a relação entre força de preensão manual, funcionalidade e fragilidade física em pessoas idosas. Método: revisão integrativa realizada nas bases de dados PubMed, CINAHL, Web of Science e Portal BVS, no período amostral de janeiro de 2010 a novembro de 2021. Empregou-se o fluxograma do Preferred Reporting Items for Systematic Reviews and Meta-analyses para apresentar a seleção dos estudos, e o nível de evidência foi avaliado a partir do Oxford Centre for Evidence-Based Medicine e as referências gerenciadas no EndNote Web. Resultados: a busca inicial resultou em 211 estudos após a aplicação dos critérios de elegibilidade, sendo que 7 estudos constituíram a revisão integrativa. A força de preensão manual se revelou um importante indicador de força muscular e crucial para a funcionalidade das pessoas idosas. Quando associada a determinadas ocorrências clínicas, a força de preensão manual colabora para a redução da funcionalidade e dependência na realização das atividades de vida diária em idosos, com maior prejuízo entre aqueles com 75 anos ou mais, de forma mais significativa entre as mulheres. Conclusão: a relação entre a força de preensão reduzida e a diminuição da funcionalidade determina a condição de fragilidade física em pessoas idosas. Isso reforça a importância do investimento dos profissionais de Enfermagem em intervenções que viabilizem a manutenção da força muscular e da funcionalidade e a reversão da fragilidade física nesse segmento populacional.

RESUMEN Objetivo: analizar las publicaciones científicas sobre la relación entre la fuerza de agarre manual, la funcionalidad y la fragilidad física en ancianos. Método: revisión integradora realizada en las bases de datos PubMed, CINAHL, Web of Science y Portal BVS, desde enero de 2010 hasta noviembre de 2021. Se utilizó el diagrama de flujo de los Preferred Reporting Items for Systematic Reviews and Meta-analyses para presentar la selección de estudios, se evaluó el nivel de evidencia del Oxford Centre for Evidence-Based Medicine y se gestionaron las referencias en EndNote Web. Resultados: la búsqueda inicial dio lugar a 211 estudios, tras aplicar los criterios de elegibilidad, siete estudios constituyeron la revisión integradora. La fuerza de agarre de la mano resultó ser un indicador importante de la fuerza muscular y crucial para la funcionalidad de los ancianos. Cuando se asocia a determinadas circunstancias clínicas, la fuerza de la presión manual contribuye a la reducción de la funcionalidad y la dependencia en la realización de las actividades de la vida diaria en los individuos, con mayor prejuicio entre los que tienen 75 años o más y de forma más significativa entre las mujeres. Conclusión: la relación entre la fuerza de agarre reducida y la disminución de la funcionalidad determina la condición de fragilidad física en los ancianos. Esto refuerza la importancia de que los profesionales de Enfermería inviertan en intervenciones que permitan mantener la fuerza y la funcionalidad muscular y revertir la fragilidad física en este segmento de la población.

ABSTRACT Objective: to analyze scientific publications on the relationship between handgrip strength, functionality, and physical frailty in the elderly. Method: integrative review carried out in PubMed, CINAHL, Web of Science and VHL Portal databases, in the sample period from January 2010 to November 2021. The Preferred Reporting Items for Systematic Reviews and Meta-analyses flowchart was used to present the selection of studies, and the level of evidence was assessed from the Oxford Center for Evidence-Based Medicine and references managed in EndNote Web. Results: the initial search resulted in 211 studies after applying the eligibility criteria, with 7 studies constituting the integrative review. Handgrip strength proved to be an important indicator of muscle strength and crucial for the functionality of elderly people. When associated with certain clinical occurrences, handgrip strength contributes to the reduction of functionality and dependence in carrying out activities of daily living in the elderly, with greater impairment among those aged 75 years or older, more significantly among women. Conclusion: the relationship between reduced grip strength and decreased functionality determines the condition of physical frailty in elderly people. This reinforces the importance of investment by Nursing professionals in interventions that enable the maintenance of muscle strength and functionality and the reversal of physical frailty in this population segment.

Kinematic characteristics during gait in frail older women identified by principal component analysis.

Frailty is associated with gait variability in several quantitative parameters, including high stride time variability. However, the associations between joint kinematics during walking and increased gait variability with frailty remain unclear. In the current study, principal component analysis was used to identify the key joint kinematics characteristics of gait related to frailty. We analyzed whole kinematic waveforms during the entire gait cycle obtained from the pelvis and lower limb joint angle in 30 older women (frail/prefrail: 15 participants; non-frail: 15 participants). Principal component analysis was conducted using a 60 × 1224 input matrix constructed from participants' time-normalized pelvic and lower-limb-joint angles along three axes (each leg of 30 participants, 51 time points, four angles, three axes, and two variables). Statistical analyses revealed that only principal component vectors 6 and 9 were related to frailty. Recombining the joint kinematics corresponding to these principal component vectors revealed that frail older women tended to exhibit greater variability of knee- and ankle-joint angles in the sagittal plane while walking compared with non-frail older women. We concluded that greater variability of knee- and ankle-joint angles in the sagittal plane are joint kinematic characteristics of gait related to frailty.

The association between heart rate behavior and gait performance: The moderating effect of frailty.

INTRODUCTION: Research suggests that frailty not only influence individual systems, but also it affects the interconnection between them. However, no study exists to show how the interplay between cardiovascular and motor performance is compromised with frailty. AIM: To investigate the effect of frailty on the association between heart rate (HR) dynamics and gait performance. METHODS: Eighty-five older adults (≥65 years and able to walk 9.14 meters) were recruited (October 2016-March 2018) and categorized into 26 non-frail (age = 78.65±7.46 years) and 59 pre-frail/frail individuals (age = 81.01±8.17) based on the Fried frailty phenotype. Participants performed gait tasks while equipped with a wearable electrocardiogram (ECG) sensor attached to the chest, as well as wearable gyroscopes for gait assessment. HR dynamic parameters were extracted, including time to peak HR and percentage increase in HR in response to walking. Using the gyroscope sensors gait parameters were recorded including stride length, stride velocity, mean swing velocity, and double support. RESULTS: Among the pre-frail/frail group, time to peak HR was significantly correlated with all gait parameters (p<0.0001, r = 0.51-0.59); however, for the non-frail group, none of the correlations between HR dynamics and gait performance parameters were significant (p>0.45, r = 0.03-0.15). The moderation analysis of time to peak HR, demonstrated a significant interaction effect of HR dynamics and frailty status on walking velocity (p<0.01), and the interaction effect was marginally non-significant for other gait parameters (p>0.10). CONCLUSIONS: Current findings, for the first time, suggest that a compromised motor and cardiac autonomic interaction exist among pre-frail/frail older adults; an impaired HR performance (i.e., slower increase of HR in response to stressors) may lead to a slower walking performance. Assessing physical performance and its corresponding HR behavior should be studied as a tool for frailty screening and providing insights about the underlying cardiovascular-related mechanism leading to physical frailty.

Implementation of an integrated home internet of things system for vulnerable older adults using a frailty-centered approach.

Although integrated home internet of things (IoT) services can be beneficial, especially for vulnerable older adults, the hurdle of usability hinders implementation of the technology. This study aimed to evaluate the practical usability of home IoT services in older adults, by frailty status, and to determine the potential obstacles. From August 2019 to July 2020, we randomly selected 20 vulnerable older adults (prefrailty group [n = 11], and frailty group [n = 9]) who had already been identified as needing home IoT services in a community-based prospective cohort study, the Aging Study of the Pyeongchang Rural Area. Integrated home IoT services were provided for 1 year, and a face-to-face survey evaluating usability and satisfaction of each service was conducted. The usability of the integrated home IoT services declined gradually throughout the study. However, prefrail participants showed higher usability than frail older adults (difference-in-difference = - 19.431, p = 0.012). According to the frailty status, the change in usability for each service type also showed a different pattern. During the 12-month study period, the service with the highest satisfaction converged from various service needs to light control by remote control (77.8%) in the prefrailty group and automatic gas circuit breaker (72.7%) in the frailty group. For wider implementation of home IoT services, organizing services expected to have high usability and satisfaction based on user's frailty status is crucial. Also, providing education before service implementation might help older adults coping with digital literacy.

Correlation of physical and cognitive impairment in diabetic and hypertensive frail older adults.

BACKGROUND: Diabetes and hypertension are common in older adults and represent established risk factors for frailty. Frailty is a multidimensional condition due to reserve loss and susceptibility to stressors with a high risk of death, hospitalizations, functional and cognitive impairment. Comorbidities such as diabetes and hypertension play a key role in increasing the risk of mortality, hospitalization, and disability. Moreover, frail patients with diabetes and hypertension are known to have an increased risk of cognitive and physical impairment. Nevertheless, no study assessed the correlation between physical and cognitive impairment in frail older adults with diabetes and hypertension. METHODS: We evaluated consecutive frail older patients with diabetes and hypertension who presented at ASL (local health unit of the Italian Ministry of Health) Avellino, Italy, from March 2021 to October 2021. The inclusion criteria were: a previous diagnosis of diabetes and hypertension with no evidence of secondary causes; age > 65 years; a frailty status; Montreal Cognitive Assessment (MoCA) score < 26. RESULTS: 179 patients successfully completed the study. We found a strong and significant correlation between MoCA score and 5-m gait speed test (r: 0.877; p < 0.001). To further verify our results, we performed a linear multivariate analysis adjusting for potential confounding factors, with MoCA score as dependent variable, which confirmed the significant association with glycemia (p < 0.001). CONCLUSIONS: This is the first study showing a significant correlation between 5-m gait speed test and MoCA score in frail diabetic and hypertensive older adults.

Exercise Capacity and Frailty Are Associated with Cerebral White Matter Hyperintensity in Older Adults with Cardiovascular Disease.

Cerebral white matter hyperintensity (WMH) is highly prevalent among older adults. There is little information about the relationship among WMH extent, frailty status, and exercise capacity in older adults with cardiovascular disease (CVD). We assessed the association of WMH with frailty and exercise capacity in CVD patients.Seventy-eight stable older adults with CVD were evaluated for WMH, the Kihon Checklist (KCL), short physical performance battery score (SPPB), and cardiopulmonary exercise testing. WMH volume was quantified on brain magnetic resonance imaging. Patients were classified into 3 groups (using tertiles of 0.52% and 1.05%) according to WMH as a percentage of intracranial volume (ICV), and their KCL scores and exercise capacities were compared. The 3 WMH/ICV groups were mild (n = 26, 0.26% ± 0.14% of intracranial volume), moderate (n = 26, 0.70% ± 0.15%), and severe (n = 26, 1.75% ± 0.67%). Peak VO2 was 15.2 ± 3.7 mL kg-1 minute-1 (mild group), 12.9 ± 3.5 mL kg-1 min-1 (moderate), and 11.4 ± 2.3 mL kg-1 minute-1 (severe) (mild versus moderate, P = 0.049; mild versus severe, P = 0.001). Multivariate regression analysis showed significant associations of severe WMH/ICV with peak VO2 and SPPB. Cerebral WMH was strongly negatively associated with SPPB and peak VO2. WMH volume may be related to exercise capacity and frailty in stable older adult patients with CVD.

Prehabilitation, enhanced recovery after surgery, or both? A narrative review.

This narrative review presents a biological rationale and evidence to describe how the preoperative condition of the patient contributes to postoperative morbidity. Any preoperative condition that prevents a patient from tolerating the physiological stress of surgery (e.g. poor cardiopulmonary reserve, sarcopaenia), impairs the stress response (e.g. malnutrition, frailty), and/or augments the catabolic response to stress (e.g. insulin resistance) is a risk factor for poor surgical outcomes. Prehabilitation interventions that include exercise, nutrition, and psychosocial components can be applied before surgery to strengthen physiological reserve and enhance functional capacity, which, in turn, supports recovery through attaining surgical resilience. Prehabilitation complements Enhanced Recovery After Surgery (ERAS) care to achieve optimal patient outcomes because recovery is not a passive process and it begins preoperatively.

Neurophysiological and Brain Structural Markers of Cognitive Frailty Differ from Alzheimer's Disease.

With increasing life span and prevalence of dementia, it is important to understand the mechanisms of cognitive aging. Here, we focus on a subgroup of the population we term "cognitively frail," defined by reduced cognitive function in the absence of subjective memory complaints, or a clinical diagnosis of dementia. Cognitive frailty is distinct from cognitive impairment caused by physical frailty. It has been proposed to be a precursor to Alzheimer's disease, but may alternatively represent one end of a nonpathologic spectrum of cognitive aging. We test these hypotheses in humans of both sexes, by comparing the structural and neurophysiological properties of a community-based cohort of cognitive frail adults, to people presenting clinically with diagnoses of Alzheimer's disease or mild cognitive impairment, and community-based cognitively typical older adults. Cognitive performance of the cognitively frail was similar to those with mild cognitive impairment. We used a novel cross-modal paired-associates task that presented images followed by sounds, to induce physiological responses of novelty and associative mismatch, recorded by EEG/MEG. Both controls and cognitively frail showed stronger mismatch responses and larger temporal gray matter volume, compared with people with mild cognitive impairment and Alzheimer's disease. Our results suggest that community-based cognitively frail represents a spectrum of normal aging rather than incipient Alzheimer's disease, despite similar cognitive function. Lower lifelong cognitive reserve, hearing impairment, and cardiovascular comorbidities might contribute to the etiology of the cognitive frailty. Critically, community-based cohorts of older adults with low cognitive performance should not be interpreted as representing undiagnosed Alzheimer's disease.SIGNIFICANCE STATEMENT The current study investigates the neural signatures of cognitive frailty in relation to healthy aging and Alzheimer's disease. We focus on the cognitive aspect of frailty and show that, despite performing similarly to the patients with mild cognitive impairment, a cohort of community-based adults with poor cognitive performance do not show structural atrophy or neurophysiological signatures of Alzheimer's disease. Our results call for caution before assuming that cognitive frailty represents latent Alzheimer's disease. Instead, the cognitive underperformance of cognitively frail adults could result in cumulative effects of multiple psychosocial risk factors over the lifespan, and medical comorbidities.

Gait speed is a preoperative indicator of postoperative events after elective proximal aortic surgery.

OBJECTIVE: The study objective was to evaluate whether 5-m gait speed, an established marker of frailty, is associated with postoperative events after elective proximal aortic surgery. METHODS: We performed a retrospective review of 435 patients aged more than 60 years who underwent elective proximal aortic surgery, defined as surgery on the aortic root, ascending aorta, or aortic arch through median sternotomy. Patients completed a 5-m gait speed test within 30 days before surgery. We evaluated the association between categoric (slow, ≤0.83 m/s and normal, >0.83 m/s) and continuous gait speed and the likelihood of experiencing the composite outcome before and after adjustment for European System for Cardiac Operative Risk Evaluation II. The composite outcome included in-hospital mortality, renal failure, prolonged ventilation, and discharge location. Secondary outcomes were 1-year mortality and 5-year survival. RESULTS: Of the study population, 30.3% (132/435) were categorized as slow. Slow walkers were significantly more likely to have in-hospital mortality, prolonged ventilation, and renal failure, and were less likely to be discharged home (all P < .05). The composite outcome was 2 times more likely to occur for slow walkers (gait speed categoric adjusted odds ratio, 2.08; 95% confidence interval, 1.27-3.40; P = .004). Moreover, a unit (1 m/s) increase in gait speed (continuous) was associated with 73% lower risk of experiencing the composite outcome (odds ratio, 0.27; 95% confidence interval, 0.11-0.68; P = .006). CONCLUSIONS: Slow gait speed is a preoperative indicator of risk for postoperative events after elective proximal aortic surgery. Gait speed may be an important tool to complement existing operative risk models, and its application may identify patients who may benefit from presurgical and postsurgical rehabilitation.

A single center's 15-year experience with palliative limb care for chronic limb threatening ischemia in frail patients.

OBJECTIVE: Our institution's multidisciplinary Prevention of Amputation in Veterans Everywhere (PAVE) program allocates veterans with critical limb threatening ischemia (CLTI) to immediate revascularization, conservative care, primary amputation, or palliative limb care according to previously reported criteria. These four groups align with the approaches outlined by the global guidelines for the management of CLTI. In the present study, we have delineated the natural history of the palliative limb care group of patients and quantified the procedural risks and outcomes. METHODS: Veterans prospectively enrolled into the palliative limb cohort of our PAVE program from January 2005 to January 2020 were analyzed. The primary outcome was mortality. The secondary outcomes included overall and limb-related readmissions, limb loss, and wound healing. The clinical frailty scale (CFS) score was calculated, and the 5-year expected mortality was estimated using the Veterans Affairs Quality Enhancement Research Initiative tool. Regression analysis was performed to establish associations among the following variables: mortality, wound, ischemia, and foot infection (WIfI) score, CFS score, overall admissions, and limb-related admissions. RESULTS: The PAVE program enrolled 1158 limbs during 15 years. Of the 1158 limbs, 157 (13.5%) in 145 patients were allocated to the palliative limb care group. The overall mortality of the group was 88.2% (median interval, 3.5 months; range, 0-91 months). Of the 128 patients who had died, 64 (50%) had died within 3 months of enrollment. The predicted 5-year mortality for the group was 66%. The average CFS score for the group was 6.2, denoting persons moderately to severely frail. Using the CFS score, 106 patients were considered frail and 39 were considered not frail. No differences were found in mortality between the frail and nonfrail patients. However, a statistically significant difference was found in early (<3 months) mortality (56.2% vs 37.5%; P = .032). The 30-day limb-related readmission rate was 4.7%. Eventual major amputation was necessary for 18 limbs (11.5%). Wound healing occurred in 30 patients (20.6%). Regression analysis demonstrated no association between the CFS score and mortality (r = 0.55; P = .159) or between the WIfI score and mortality (r = 0.0165; P = .98). However, a significant association was found between the WIfI score and limb-related admissions (r = 0.97; P < .001). CONCLUSIONS: Frail patients with CLTI had high early mortality and a low risk of limb-related complications. They also had a low incidence of deferred primary amputation or limb-related readmissions. In our cohort, the vast majority of patients had died within a few months of enrollment without requiring an amputation. A comprehensive approach to the treatment of CLTI patients should include a palliative limb care option because a significant proportion of these patients will have limited survival and can potentially avoid unnecessary surgery and major amputation.

Systolic Blood Pressure and Mortality in Community-Dwelling Older Adults: Frailty as an Effect Modifier.

Current evidence is insufficient to support different hypertension treatment targets in older adults. We evaluated whether frailty modifies the association between systolic blood pressure (SBP) and 8-year all-cause mortality in community-dwelling older adults. Longitudinal data from the ActiFE Ulm study (Activity and Function in the Elderly in Ulm; Germany) was collected. The association between SBP and mortality was analyzed using Cox proportional hazards models adjusted for age, sex, education, smoking, alcohol consumption, sleep disturbance, diastolic blood pressure, and antihypertensive medications, evaluating the presence of effect modification by frailty according to a frailty index based on the accumulation of deficits. Among 1170 participants (median age 73.9 years, 41.6% women), the prevalence of history of hypertension was 53.8% (median SBP, 144.0 mm Hg [interquartile range, 135.0-149.5], median diastolic blood pressure 78.0 mm Hg [interquartile range, 71.0-86.5]). The median follow-up time was 8.1 years, detecting 268 deaths. We identified 251 (21.5%, 114 deaths) frail participants (frailty index ≥0.2). Effect modification by frailty was detected. Among non-frail a J-shaped association was found with hazard ratio, 4.01 (95% CI, 1.13-14.28) for SBP<110 mm Hg, hazard ratio, 0.92 (95% CI, 0.53-1.59) for SBP 140-150 mm Hg, and hazard ratio, 1.98 (95% CI, 0.75-5.27) for SBP≥160 mm Hg. For frail older adults, a tendency toward lower risk among those with SBP≥130 mm Hg was observed. Our results suggest the presence of effect modification by frailty indicating a possible protective effect for elevated SBP in frail older adults with respect to all-cause mortality even after adjusting for diastolic blood pressure and antihypertensive treatment.

Inflammatory Bowel Disease Patients Who Respond to Treatment with Anti-tumor Necrosis Factor Agents Demonstrate Improvement in Pre-treatment Frailty.

BACKGROUND: Frailty may be a risk factor for complications in inflammatory bowel diseases (IBD) patients. We examined the impact of treatment on IBD patients who were frail prior to treatment and identified predictors of post-treatment change in frailty. METHODS: In an electronic health record-based cohort of IBD patients initiating anti-tumor necrosis factor (TNF)-α agents, we applied a validated claims-based frailty index to determine frailty in the 1 year prior to and after treatment initiation. We characterized treatment non-response using a composite outcome of IBD-related hospitalization, surgery, change in therapy, or initiation of systemic steroids. We constructed multivariable logistic regression models to identify determinants of post-treatment frailty. RESULTS: The 1210 patients initiating anti-TNF therapy had a median age of 30 years; 20% were ≥ 50 years. In the first year after anti-TNF initiation, 40% were non-responders. Many more treatment non-responders were frail in the year following treatment compared with treatment responders (27% vs 7%, p < 0.001). Pre-treatment frailty (OR 2.01, 95% CI 1.35-3.00) and prior IBD-related hospitalization (OR 1.63, 95% CI 1.15-2.30) were independently predictive of higher likelihood of post-treatment frailty. Therapy response was associated with a lower likelihood (OR 0.24, 95% CI 0.16-0.34) of post-treatment frailty. Nearly 85% of patients who were frail prior to treatment demonstrated improvement in frailty following treatment CONCLUSIONS: Response to anti-TNF therapy is an important determinant of post-treatment frailty in patients with IBD. Our findings suggest that effectively treating inflammatory states in older patients with IBD may improve frailty.