Myokines and Biomarkers of Frailty in Older Inpatients with Undernutrition: A Prospective Study.

BACKGROUND: Population aging might increase the prevalence of undernutrition in older people, which increases the risk of frailty. Numerous studies have indicated that myokines are released by skeletal myocytes in response to muscular contractions and might be associated with frailty. This study aimed to evaluate whether myokines are biomarkers of frailty in older inpatients with undernutrition. METHODS: The frailty biomarkers were extracted from the Gene Expression Omnibus and Genecards datasets. Relevant myokines and health-related variables were assessed in 55 inpatients aged ≥ 65 years from the Peking Union Medical College Hospital prospective longitudinal frailty study. Serum was prepared for enzyme-linked immunosorbent assay using the appropriate kits. Correlations between biomarkers and frailty status were calculated by Spearman's correlation analysis. Multiple linear regression was performed to investigate the association between factors and frailty scores. RESULTS: The prevalence of frailty was 13.21%. The bioinformatics analysis indicated that leptin, adenosine 5'-monophosphate-activated protein kinase (AMPK), irisin, decorin, and myostatin were potential biomarkers of frailty. The frailty group had significantly higher concentrations of leptin, AMPK, and MSTN than the robust group (p < 0.05). AMPK was significantly positively correlated with frailty (p < 0.05). The pre-frailty and frailty groups had significantly lower concentrations of irisin than the robust group (p < 0.05), whereas the DCN concentration did not differ among the groups. Multiple linear regression suggested that the 15 factors influencing the coefficients of association, the top 50% were the ADL score, MNA-SF score, serum albumin concentration, urination function, hearing function, leptin concentration, GDS-15 score, and MSTN concentration. CONCLUSIONS: Proinflammatory myokines, particularly leptin, myostatin, and AMPK, negatively affect muscle mass and strength in older adults. ADL and nutritional status play major roles in the development of frailty. Our results confirm that identification of frailty relies upon clinical variables, myokine concentrations, and functional parameters, which might enable the identification and monitoring of frailty.

Yubi-Wakka Test for Sarcopenia Screening in the Community: Comparative Agreement, Diagnostic Performance and Validity with Calf Circumference Measurements.

BACKGROUND: Screening tools such as calf circumference (CC) and Yubi-wakka (finger-ring) test have been recognized as effective tools by Asian Working Group for Sarcopenia 2019 (AWGS'19) for sarcopenia screening but their comparative agreement, diagnostic performance and validity are unclear. OBJECTIVES: This study aims to determine: (i)agreement between calf and finger-ring circumference, (ii)diagnostic performance for low muscle mass and AWGS'19 sarcopenia diagnosis, (iii)correlation with muscle mass, strength, and physical performance, and (iv)association with frailty, life space mobility and physical activity. METHODS: We studied 187 healthy community-dwelling older adults (mean age=66.8+7.0years) from the GERILABS-2 study. CC was measured via (i) both calves in sitting and standing positions, and (ii) Yubi-wakka test by encircling the thickest part of the non-dominant calf with index fingers and thumbs of both hands. We performed Cohen's kappa to check for agreement, area under receiver operating characteristic curve (AUC) to compare diagnostic performance, partial correlations adjusted for age and gender to compare convergent validity, and logistic regression to determine predictive validity for outcome measures. RESULTS: Sarcopenia prevalence was 24.0% (AWGS'19). Yubi-wakka identified 16.6% of participants as screen-positive ("smaller"), showing moderate agreement only with non-dominant sitting CC measurements (k=0.421,p<0.001) and having lower diagnostic performance in determining low muscle mass (AUC=0.591 vs 0.855-0.870,p<0.001; sensitivity=57.1% vs 75.5-90.8%; specificity=58.4% vs 70.8-80.9%) and sarcopenia diagnosis (AUC=0.581 vs 0.788-0.818,p<0.001; sensitivity=55.6% vs 57.5-71.8%; specificity=74.4% vs 75.6-88.9%) compared to CC measurements. Yubi-wakka correlated significantly with muscle mass, grip strength and knee extension but not physical performance. When adjusted for age, gender and hypertension, Yubi-wakka was significantly associated with frailty (OR=3.96,95%CI:1.09-14.38), life space mobility (OR=2.38,95%CI:1.08-5.24) and physical activity (OR=2.50,95%CI:1.07-5.86). DISCUSSION AND CONCLUSIONS: Yubi-wakka provides a self-administered, low-cost and practicable community screening tool for sarcopenia. Our study affirmed the convergent and predictive validity of Yubi-wakka, albeit with lower sensitivity and specificity in diagnostic performance compared to CC measurements.

Co-Occurrence of Sarcopenia and Frailty in Acutely Admitted Older Medical Patients: Results from the Copenhagen PROTECT Study.

BACKGROUND: Sarcopenia and frailty are often used interchangeably in clinical practice yet represent two distinct conditions and require different therapeutic approaches. The literature regarding the co-occurrence of both conditions in older patients is scarce as most studies have investigated the prevalence of sarcopenia and frailty separately. OBJECTIVES: We aim to evaluate the prevalence and co-occurrence of sarcopenia and frailty in a large sample of acutely admitted older medical patients. DESIGN: Secondary analyses using cross-sectional data from the Copenhagen PROTECT study. SETTING: Patients were included from the acute medical ward at Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark, between November 2019 and November 2021. PARTICIPANTS: Acutely admitted older medical patients (≥65 years). MEASUREMENTS: Handgrip strength (HGS) was investigated using a handheld dynamometer. Lean mass (SMI) was investigated using direct-segmental multifrequency bioelectrical impedance analyses (DSM-BIA). Low HGS, low SMI, and sarcopenia were defined according to the recent definitions from the European Working Group on Sarcopenia in Older People (EWGSOP2). The Clinical Frailty Scale (CFS) was used to evaluate frailty, with a value > 5 indicating the presence of frailty. Patients were enrolled and tested within 24 hours of admission. RESULTS: This study included 638 patients (mean age: 78.2±7.6, 55% female) with complete records of SMI, HGS, and the CFS. The prevalence of low HGS, low SMI, sarcopenia, and frailty were 39.0%, 33.1%, 19.7%, and 39.0%, respectively. Sarcopenia and frailty co-occurred in 12.1% of the patients. CONCLUSIONS: It is well-known that sarcopenia and frailty represent clinical manifestations of ageing and overlap in terms of the impairment in physical function observed in both conditions. Our results demonstrate that sarcopenia and frailty do not necessarily co-occur within the older acutely admitted patient, highlighting the need for separate assessments of frailty and sarcopenia to ensure the accurate characterization of the health status of older patients.

Dose-Responsive Impacts of Social Frailty on Intrinsic Capacity and Healthy Aging among Community-Dwelling Middle-aged and Older Adults: Stronger Roles of Social Determinants over Biomarkers.

OBJECTIVE: The intricate relationship between social determinants, e.g., social frailty, biomarkers and healthy aging remains largely unexplored, despite the potential for social frailty to impact both intrinsic capacity (IC) and functional ability in the aging process. DESIGN: Retrospective longitudinal cohort study. SETTING AND PARTICIPANTS: Participants aged 50+ years from the Social Environment and Biomarkers of Aging Study (SEBAS) in Taiwan, stratified into three age groups: 50-64, 65-74 and 75+. MEASUREMENTS: Social frailty was defined based on a score derived from four domains: exclusion from general resources, social resources, social activity, and fulfillment of basic social needs. The scores were categorized as score=0 (no social frailty), 1 (social pre-frailty), and 2+ (social frailty). Multivariable logistic regression and Cox proportional hazard models were employed to examine the dose-responsive relationship between social frailty, low IC, functional and psychological health, and mortality. RESULTS: Of 1015 study participants, 24.9% and 7.9% were classified as social pre-frailty and social frailty, respectively. No significant differences were observed in most biomarkers between those with social frailty and those without. A dose-responsive relationship was found between social frailty and increased risk of low IC (social pre-frailty: aOR 2.20 [95% CI 1.59-3.04]; social frailty: 5.73 [3.39-9.69]). Similar results were found for functional and psychological health. However, no significant association between social frailty and all-cause mortality was found at the 4-year follow-up (social pre-frailty: aHR 1.52 [95% CI 0.94-2.43]; social frailty: 1.59 [0.81-3.09]). CONCLUSIONS: The significant association between social frailty and low IC, functional limitations, cognitive declines, and depressive symptoms underscores the pressing need for research on intervention strategies to enhance healthy aging in the lifespan course.

Loneliness Predicts Progression of Frailty in Married and Widowed, but Not Unmarried Community Dwelling Older Adults.

BACKGROUND: Loneliness is highly prevalent among older adults and is associated with frailty. Most studies consider loneliness in isolation without consideration for structural and functional measures of social relationships - and longitudinal studies are scarce. OBJECTIVES: This study examined longitudinal associations between loneliness and frailty and analyzed how structural and functional social measures influence these associations. DESIGN: Linear mixed effects models examined longitudinal associations between loneliness and frailty assessed with the frailty index (scale 0-100). Models were adjusted for baseline age, gender, education, depressive symptoms, global cognition, and structural (e.g., social network, marital status), and functional social measures (e.g., social, cognitive, and physical activity, and social support). PARTICIPANTS: Loneliness and frailty data from 1,931 older adults without dementia at baseline from the Rush Memory and Aging Project were examined (mean age 79.6 ± 7.7 years, 74.9% female). MEASUREMENTS: Baseline loneliness assessed by the de Jong Gierveld Loneliness Scale was the predictor of interest. RESULTS: Frailty increased significantly over a mean follow-up period of 4.6 years. Effects of loneliness on frailty were modified by marital status. Loneliness predicted an additional accumulation of 0.37 and 0.34 deficits on the frailty index per year in married and widowed individuals respectively, compared to those who were not lonely (married: p=0.009, CI 0.09, 0.64; widowed: p=0.005, CI 0.1, 0.58). Loneliness did not predict frailty progression in unmarried individuals. CONCLUSIONS: Loneliness predicts frailty progression, highlighting the importance of social determinants on physical health in aging.

Serum Creatinine-Cystatin C Based Screening of Sarcopenia in Community Dwelling Older Adults: A Cross-Sectional Analysis.

OBJECTIVES: To compare the discriminative capabilities for the manifestation of sarcopenia or physical frailty between serum creatinine- and cystatin C-derived indices among community-dwelling older adults. DESIGN: Cross-sectional study. SETTING: Primary Care and Community. PARTICIPANTS: We utilized a subset of data from the Frail Elderly in the Sasayama-Tamba Area (FESTA) study, which was initiated in 2015 to gather comprehensive information on various health-related parameters among community-dwelling older individuals (age ≥65 years). MEASUREMENTS: Five serum creatinine-cystatin C based indices including the Sarcopenia Index, the serum creatinine/cystatin C ratio, the disparity between serum cystatin-C-based and creatinine-based estimated GFR, the total body muscle mass index (TBMM), and the prediction equation for skeletal muscle mass index (pSMI) were employed. Sarcopenia and physical frailty were identified based on the Asian Working Group for Sarcopenia criteria and the revised Japanese version of the Cardiovascular Health Study criteria, respectively. The receiver operating characteristic (ROC) and logistic regression analyses were performed to assess the discriminative abilities of these tools. RESULTS: In the analysis of 954 participants, 52 (5.5%) were identified with sarcopenia and 35 (3.7%) with physical frailty. Regarding sarcopenia discrimination, TBMM and pSMI both exhibited area under the curve (AUC) values exceeding 0.8 for both men and women. Concerning the identification of physical frailty, AUC values ranged from 0.61 to 0.77 for males and 0.50 to 0.69 for females. In the multivariate logistic regression analyses, only TBMM and pSMI consistently displayed associations with sarcopenia, irrespective of sex (P<0.001, respectively). On the other hand, no consistent associations were observed between the indices and physical frailty. CONCLUSIONS: This study provides a robust association of a serum creatinine- and cystatin C-derived indices, especially TBMM and pSMI, with sarcopenia among community-dwelling older adults. Conversely, the application of these indices for the screening of physical frailty has its constraints, necessitating further investigation.

The Impact of Exercise and Cognitive Stimulation Therapy on Intrinsic Capacity Composite Score in Pre-Frail Older Adults: A Pre-Post Intervention Study.

Intrinsic capacity(IC) is a measure of physical, cognitive, vitality, psychological, and sensory abilities which determines functional ability. Decline in IC has been shown to accelerate the trajectory of frailty. We aim to show the impact of exercise (Ex) and cognitive stimulation therapy (CST) on (i) IC domains and composite score (ii) frailty and functional ability in pre-frail older adults. Secondary analysis of data from a pre-post intervention study of pre-frail older adults ≥ 65 years attending primary care clinic. Control (CON) and 2 intervention groups ((i) Ex 6 months (ii) CST 3 months with Ex 6 months (Ex+CST)) were recruited. Pre-frailty was determined using the FRAIL scale. Questionnaires (on demographics, functional ability, and depression) were administered and physical function assessment (gait speed (GS), short physical performance battery (SPPB) test, handgrip strength, five times sit-to-stand (5x-STS)) was conducted at 0, 3, 6 and 12 months. Four domains of IC were evaluated: locomotion (GS and 5x-STS), vitality (nutrition and muscle mass), cognition (MoCA and subjective cognitive decline) and psychological (depression and anxiety). Each domain was scored from 0 to 2 (no decline) with total IC score ranging from 0 to 8. 187 participants completed baseline and 3 months assessments, 109 (58.3%) were allocated to CON, 37 (19.8%) to Ex and 41 (21.9%) to Ex + CST groups. At 3 months, both Ex and Ex +CST showed improvement in IC composite scores, locomotion, and psychological domain scores but improvement in cognition domain only in Ex + CST group. At 6 months, there were improvements in total IC score, locomotion, vitality, and psychological domain in both Ex and Ex + CST groups. At 12 months, significant improvement was evident in total IC score for Ex and Ex+CST groups, vitality when fatigue (in addition to muscle mass and nutrition) was added and instrumental activities of daily living. Multidomain intervention incorporating exercise and CST resulted in significant improvement in IC composite scores, locomotion, vitality, cognition, and psychological domains.

Identifying Frailty in Administrative Databases: A Narrative Review.

Frailty is a state of increased vulnerability that can lead to premature death. While various clinical tools effectively measure frailty in individual care, their applicability at the population-level is limited. However, in the era of big-data, administrative databases serve as valuable sources for medication-based research and population surveillance. This narrative scoping review synthesizes the literature on tools used within administrative databases to detect frailty in community-dwelling older adults. The 17 identified publications explore four tools that meet the criteria of the Rockwood and Mitnitski frailty index model. Despite variations in the deficits they incorporate, all tools appear to be valuable for identifying frailty and predicting the risk of adverse events. Using those tools within administrative databases can be useful for research and surveillance purposes.

Combined Social Frailty and Life-Space Activities Associated with Risk of Disability: A Prospective Cohort Study.

OBJECTIVES: To examine the association between social frailty and life-space activities, and determine whether a combined status of life-space activities and social frailty is associated with risk of disability among older adults. DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: The participants were 8,301 older adults (mean age 72.9 ± 5.6 years, women [53.3%]) from a community setting. METHODS: Life-space activities were evaluated using the Active Mobility Index (AMI) to assess activities in each life-space (distance from the respondent's home: up to 1 km, 1-10 km, or greater than 10 km) during the past 1 month. Activities were also assessed according to physical or social activity. Social frailty and characteristics were measured at the baseline. Incident disability was assessed according to long term care insurance. RESULTS: The lowest scoring group was based on the quartile in each of the AMI scores (Q1), with reference to the highest scoring group, which had a higher odds ratios for social frailty (AMI total score Q1: OR 4.32, 95% CI 3.43-5.45, AMI physical score Q1: 2.19, 95% CI 1.79-2.69, AMI social score Q1: 5.04, 95% CI 3.94-6.44). During the follow-up (mean 23.5 months), 330 participants had incident disability. Incident disability was associated with social frailty. Combined status of social frailty and low AMI increased the risk of disability (HR 2.15, 95% CI 1.52-3.03), with reference to non-frailty and higher AMI scores. CONCLUSIONS AND IMPLICATIONS: Social frailty or reduced activity in life-space assessment were identified as risk factors for incident disability. To decrease the risk of disability, the development of an intervention program to enhance activities and cope with social frailty is required.

Teaching Frailty to Medical Residents: A Needs Assessment Among Geriatrics Faculty.

BACKGROUND: Knowledge of frailty is essential for meeting the Accreditation Council for Graduate Medical Education core competencies for US trainees. The UK General Medical Council requires that frailty be included in undergraduate and graduate medical education curricula. Trainees are expected to appropriately modify care plans and help make patient-centered decisions, while incorporating diagnostic uncertainty, such as frailty, in older adults. Little is known about current needs for frailty instruction in graduate medical education in the US and beyond. OBJECTIVE: We sought to capture faculty perceptions on how frailty should be defined and identified, and what aspects and level of detail should be taught to residents. DESIGN: The authors developed a 4-item short response questionnaire, and faculty had the option to respond via electronic survey or via semi-structured interviews. SETTING AND SUBJECTS: Respondents included 24 fellowship-trained geriatricians based at 6 different academic medical centers in a single urban metropolitan area. METHODS: An invitation to participate in either an electronic survey or semi-structured virtual interview was e-mailed to 30 geriatricians affiliated with an academic multi-campus Geriatric Medicine fellowship. Responses were transcribed and coded independently by two authors. RESULTS: Responses were received from 24 geriatricians via a combination of digital questionnaires (n=18) and semi-structured online interviews (n=6), for a response rate of 80%. Responses revealed significant diversity of opinion on how to define and identify frailty and how these concepts should be taught. CONCLUSIONS: As frailty is increasingly incorporated into clinical practice, consensus is needed on how to define and teach frailty to residents.

Targeted metabolomic profiles of serum amino acids are independently correlated with malnutrition in older adults.

BACKGROUND: Malnutrition is a common geriatric syndrome that is closely associated with adverse clinical outcomes and poses significant harm to older adults. Early assessment of nutritional status plays a crucial role in preventing and intervening in cases of malnutrition. However, there is currently a lack of measurable methods and biomarkers to evaluate malnutrition in older adults accurately. The aim of this study is to investigate the independent correlation between serum levels of amino acids and malnutrition in older adults, and to identify effective metabolomics biomarkers that can aid in the early detection of geriatric malnutrition. METHODS: A total of 254 geriatric medical examination participants from Beijing Hospital were included in the study, consisting of 182 individuals with normal nutritional status (Normal group) and 72 patients at risk of malnutrition or already malnourished (MN group). Malnutrition was assessed using the Mini-Nutritional Assessment Short-Form (MNA-SF). Demographic data were collected, and muscle-related and lipid indexes were determined. Serum amino acid concentrations were measured using isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). The correlation between serum amino acid levels and malnutrition was analyzed using non-parametric tests, partial correlation analysis, linear regression, and logistic regression. RESULTS: The geriatric MN group exhibited significantly lower serum aromatic amino acid levels (P < 0.05) compared to the normal group. A positive correlation was observed between serum aromatic amino acid levels and the MNA-SF score (P = 0.002), as well as with known biomarkers of malnutrition such as body mass index (BMI) (P < 0.001) and hemoglobin (HGB) (P = 0.005). Multivariable logistic or linear regression analyses showed that aromatic amino acid levels were negatively correlated with MN and positively correlated with the MNA-SF score, after adjusting for some confounding factors, such as age, gender, BMI, smoking status, history of dyslipidemia, diabetes mellitus and frailty. Stratified analyses revealed that these trends were more pronounced in individuals without a history of frailty compared to those with a history of frailty, and there was an interaction between aromatic amino acid levels and frailty history (P = 0.004). CONCLUSION: Our study suggests that serum aromatic amino acids are independently associated with malnutrition in older adults. These results have important implications for identifying potential biomarkers to predict geriatric malnutrition or monitor its progression and severity, as malnutrition can result in poor clinical outcomes.

Association of Frailty with Patient-Report Outcomes and Major Clinical Determinants in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: This study aimed to explore the correlation of frailty status with disease characteristics and patient-reported outcomes (PROs) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and determine the sensitivity and specificity of modified COPD PRO scale (mCOPD-PRO) for detecting frailty. Patients and Methods: This cross-sectional study surveyed 315 inpatients with AECOPD from a tertiary hospital in China from August 2022 to June 2023. Patient frailty and PROs were assessed using the validated FRAIL scale and mCOPD-PRO, respectively. Spearman's ρ was used to assess the relevance of lung disease indicators commonly used in clinical practice, and ordinal logistic regression analyses were used to identify the variables associated with frailty status. The validity of mCOPD-PRO in discriminating frail or non-frail individuals was determined using the receiver operating characteristic curve. Results: The participants (N=302, mean age 72.4±9.1 years) were predominantly males (73.2%). Among them, 43 (14.3%) patients were not frail, whereas 123 (40.7%) and 136 (45.0%) patients were pre-frail and frail, respectively. The FRAIL scale was moderately correlated with the mCOPD-PRO scores (Spearman's rank correlation coefficient [Rs]=0.52, P<0.01) for all dimensions (Rs=0.43-0.49, P<0.01). Patients residing in rural areas (odds ratio [OR], 1.67; 95% confidence interval [95% CI], 1.01-2.76) and with higher mCOPD-PRO scores (OR, 4.78; 95% CI, 2.75-8.32) were more likely to be frail. Physically active patients (OR, 0.42; 95% CI, 0.21-0.84) were less likely to be frail. In addition, mCOPD-PRO had good discriminate validity for detecting frailty (area under the curve=0.78), with a sensitivity and specificity of 84.6% and 60.8%, respectively. The optimal probability threshold for mCOPD-PRO was ≥1.52 points. Conclusion: In patients with AECOPD, frailty is closely related to PROs and disease characteristics. Additionally, the mCOPD-PRO score can distinguish well between frail and non-frail patients. Our findings provide support for interventions targeting frail populations with AECOPD.

Patients with chronic obstructive pulmonary disease often have concomitant frailty that may lead to disease deterioration such as acute exacerbations, hospital readmissions, disability, and premature death. Patient-reported outcomes are often used in clinical practice to measure patients' disease characteristics and overall status. Whether patients' frailty state is associated with patient-reported outcomes and if so, which factors are associated with frailty remain unclear. This study, conducted in China, examined their relationship as well as identified factors associated with frailty states. 302 hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease completed a questionnaire answering questions about disease severity, frailty state, anxiety, and depression. The findings suggest that people who live in rural areas, self-reported more severe overall conditions, and are physically inactive are more likely to be frail. Patient-reported outcomes can distinguish between frail and non-frail patients. Therefore, patient-reported outcomes can be used to assess the extent of frailty; early screening of AECOPD combined frailty population and implementation of interventions can help mitigate the adverse effects of frailty.

Frailty and spatialization of older adults in the city of Uberlândia with IVCF-20.

OBJECTIVE: To describe the functional clinical profile of elderly people linked to primary health care, using the Functional Clinical Vulnerability Index (IVCF-20) and to spatialize those with the greatest functional decline by primary health care units in the municipality of Uberlândia, in the state of Minas Gerais (MG), in the year 2022. METHODS: A cross-sectional study with secondary data from the Municipal Health Department of Uberlândia-MG. The variables were compared using Student's t-test, Mann Whitney test, Pearson's chi-square, and multinomial logistic regression to obtain the independent effect of each variable. The significance level adopted was 5% (p < 0.05). The georeferenced database in ArcGIS® was used. RESULTS: 47,182 older adults were evaluated with a mean age of 70.3 years (60 to 113 years), 27,138 of whom were women (57.52%), with a clear predominance of low-risk or robust older adults (69.40%). However, 11.09% are high-risk older adults and 19.52% are at risk of frailty. Older men had independently lower odds of moderate and high risk compared to older women (OR = 0.53; p < 0.001). A high prevalence of polypharmacy was observed, 21.40% of the older adult population, particularly in frail older adults, with a prevalence of 63.08%. There was a greater distribution of frail older adults around the central region of the municipality and in health units with a larger coverage area. The IVCF-20 made it possible to screen frailty in primary health care. CONCLUSION: The instrument is capable of stratifying the risk of older adults in health care networks through primary health care, enabling the application of individualized preventive, promotional, palliative, or rehabilitative interventions, according to the clinical functional stratum of the older adult and the compromised functional domains. Risk stratification and spatial distribution of the frailest older adults can be a good strategy for qualifying health professionals with the aim of maximizing the autonomy and independence of the older adults.

Effect modification of polypharmacy on incident frailty by chronic kidney disease in older adults.

BACKGROUND: Frailty and polypharmacy are common conditions in older adults, especially in those with chronic kidney disease (CKD). Therefore, we analyzed the association of polypharmacy and incident frailty and the effect modification by CKD in very old adults. METHODS: In non-frail individuals within the Berlin Initiative (cohort) Study, polypharmacy (≥ 5 medications) was assessed according to multiple definitions based on the number of regular and on demand prescription and over the counter drugs, as well as vitamins and supplements. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73m2 and/or an albumin-creatinine ratio ≥ 30 mg/g. Incident frailty was assessed at follow-up using Fried criteria. Logistic regression was applied to assess (1) the association of different polypharmacy definitions with incident frailty and (2) effect modification by CKD. RESULTS: In this cohort study, out of 757 non-frail participants (mean age 82.9 years, 52% female, 74% CKD), 298 (39%) participants reported polypharmacy. Over the observation period of 2.1 years, 105 became frail. Individuals with polypharmacy had 1.96 adjusted odds (95% confidence interval (CI): 1.20-3.19) of becoming frail compared to participants without polypharmacy. The effect of polypharmacy on incident frailty was modified by CKD on the additive scale (relative excess risk due to interaction: 1.56; 95% CI 0.01-3.12). CONCLUSIONS: This study demonstrates an association of polypharmacy and incident frailty and suggests strong evidence for an effect modification of CKD on polypharmacy and incident frailty. Revision of prescriptions could be a target strategy to prevent frailty occurrence, especially in older adults with CKD.

Targeting belongingness among older people through engagement in senior centres: intervention development study in Denmark.

Adults often experience a loss of social relations and sense of belonging in later life, leading to the risk of social isolation. Municipal senior centres offer a potential site for intervention, as they provide social communities targeting older people. However, not all older people find it easy to access these social communities due to experiencing physical and/or psychosocial frailties and could therefore continue to experience a decline in social relations and sense of belonging, which potentiates poor physical and psychosocial health and well-being. To date, there are limited evidence-based interventions in Denmark. The present article describes the development of an intervention to increase belongingness and decrease social isolation among older people with frailties who attend Danish municipal senior centres. The development process was conducted with reference to the INDEX (IdentifyiNg and assessing different approaches to DEveloping compleX intervention) guidance. The development process resulted in a 6-month supportive intervention, consisting of four elements: skills development workshops for all staff members; a start conversation including frailty screening; allocation of a 'buddy' among existing service users; and monthly follow-up conversations with staff members. This theory-informed approach can progress to feasibility testing and outcome evaluation in order to generate an evidence base. Concurrently, the article reflects on current guidance for intervention development and how it may be used and optimized to strengthen developmental processes in the future.

Associations between breakfast skipping and outcomes in neuropsychiatric disorders, cognitive performance, and frailty: a Mendelian randomization study.

BACKGROUND: Prior studies have identified a correlation between breakfast skipping and a heightened risk of mental health issues. This investigation aimed to employ a Two-Sample Mendelian Randomization (MR) approach to explore the potential causal links between breakfast skipping and various psychiatric, neurological disorders, cognitive performance, and frailty. METHODS: Utilizing data from genome-wide association studies within European demographics, this research scrutinized the association between breakfast habits and several neuropsychiatric conditions and physical health outcomes, including Alzheimer's disease (AD), Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder (BD), Major Depressive Disorder (MDD), Narcolepsy, Insomnia, cognitive performance, and frailty. In this MR analysis, the Inverse Variance Weighted (IVW) method was primarily utilized for evaluation. Outcomes were reported as Odds Ratios (OR) and regression coefficients (ß), and underwent validation through False Discovery Rate (FDR) corrections, thereby offering a rigorous evaluation of the effects of breakfast habits on both mental and physical health dimensions. RESULTS: Findings demonstrate a significant causal link between skipping breakfast and an increased risk of ADHD (OR = 2.74, 95%CI: 1.54-4.88, PFDR = 0.003) and MDD (OR = 1.7, 95%CI: 1.22-2.37, PFDR = 0.005). Conversely, no substantial causal associations were identified between breakfast skipping and AD, BD, narcolepsy, or insomnia (PFDR > 0.05). Moreover, a notable causal relationship was established between skipping breakfast and a reduction in cognitive performance (ß = -0.16, 95%CI: -0.29-0.04, PFDR = 0.024) and an increase in frailty (ß = 0.29, 95%CI: 0.12-0.45, PFDR = 0.003). CONCLUSION: The MR analysis reveals that skipping breakfast is associated with an increased risk of ADHD, MDD, decreased cognitive performance, and greater frailty, while showing no associations were found with AD, BD, narcolepsy, or insomnia. These findings warrant further investigation into the underlying mechanisms and emphasize the importance of regular breakfast consumption for mental and physical well-being.

[Association between the severity of neurocognitive disorders and the seriousness of falls in the elderly]. / Association entre la sévérité des troubles neurocognitifs et la gravité des chutes chez les personnes âgées.

Falls cause severe morbidity and mortality in people over 65 years old in all countries. Cognitive frailty is considered to be one of the risk factors for falls in the elderly. Approximately 60% of the elderly with neurocognitive disorders fall annually and this is two times more compared to elderly with no cognitive impairment. We already know that neurocognitive disorders and their severity are a risk factor for falls in older people. Few studies are conducted to investigate the association between the severity of neurocognitive disorders and the severity of falls. This study is therefore interested in investigating the association between the severity of neurocognitive disorders and the serious falls in the elderly. This is a non-interventional retrospective study of 100 patients admitted for fall in a geriatric hospital. The correlation between MMSE and fall severity remains uncertain. Serious falls are more frequent in patients with Parkinsonian syndromes, but this result is not statically significant. Polypharmacy remains very prevalent in our population with 70 % of patients having more than four drugs. Polydrug use in our study was very high, with 70% of patients taking more than four medications. We did not find a statistically significant association between the severity of neurocognitive disorders evaluated with the MMSE and the serious falls. More studies with tailored neurocognitive testing are needed to investigate the link between executive function disorders and the serious of falls.

Lifestyle-related factors in late midlife as predictors of frailty from late midlife into old age: a longitudinal birth cohort study.

BACKGROUND: Few studies have examined longitudinal changes in lifestyle-related factors and frailty. METHODS: We examined the association between individual lifestyle factors (exercise, diet, sleep, alcohol, smoking and body composition), their sum at baseline, their change over the 17-year follow-up and the rate of change in frailty index values using linear mixed models in a cohort of 2,000 participants aged 57-69 years at baseline. RESULTS: A higher number of healthy lifestyle-related factors at baseline was associated with lower levels of frailty but not with its rate of change from late midlife into old age. Participants who stopped exercising regularly (adjusted ß × Time = 0.19, 95%CI = 0.10, 0.27) and who began experiencing sleeping difficulties (adjusted ß × Time = 0.20, 95%CI = 0.10, 0.31) experienced more rapid increases in frailty from late midlife into old age. Conversely, those whose sleep improved (adjusted ß × Time = -0.10, 95%CI = -0.23, -0.01) showed a slower increase in frailty from late midlife onwards. Participants letting go of lifestyle-related factors (decline by 3+ factors vs. no change) became more frail faster from late midlife into old age (adjusted ß × Time = 0.16, 95% CI = 0.01, 0.30). CONCLUSIONS: Lifestyle-related differences in frailty were already evident in late midlife and persisted into old age. Adopting one new healthy lifestyle-related factor had a small impact on a slightly less steeply increasing level of frailty. Maintaining regular exercise and sleeping habits may help prevent more rapid increases in frailty.

Determinants of health status in older patients with transthyretin cardiac amyloidosis: a prospective cohort study.

BACKGROUND: Whether, and to what extent, frailty and other geriatric domains are linked to health status in patients with transthyretin cardiac amyloidosis (ATTR-CA) is unknown. AIMS: To determine the association of frailty with health status [defined by the Kansas City Cardiomyopathy Questionnaire (KCCQ)] in patients with ATTR-CA. METHODS: Consecutive ATTR-CA patients undergoing cardiovascular assessment at a tertiary care clinic from September 2021 to September 2023 were invited to participate. KCCQ, frailty and social environment were recorded. Frailty was assessed using the modified Frailty Index (mFI), mapping 11 variables from the Canadian Study of Health and Aging (frailty ≥0.36). RESULTS: Of 168 screened ATTR-CA patients, 138 [83% men, median age of 79 (75-84) years] were enrolled in the study. Median KCCQ was 66 (50-75). wtATTR-CA was the most prevalent form (N = 113, 81.9%). The most frequent cardiac variant was Ile68Leu (17/25 individuals with vATTR-CA). Twenty (14.5%) patients were considered frail, and prevalence of overt disability was 6.5%. At multivariable linear regression analysis, factors associated with worsening KCCQ were age at evaluation, the mFI, NYHA Class, and NAC Score. Gender, ATTR-CA type, phenotype, and LVEF were not associated with health status. DISCUSSION: In older patients diagnosed with ATTR-CA, frailty, symptoms, and disease severity were associated with KCCQ. CONCLUSIONS: Functional status is a determinant of quality of life and health status in older individuals with a main diagnosis of ATTR-CA. Future research may provide more in-depth knowledge on the association of frailty in patients with ATTR-CA with respect to quality of life and prognosis.