Low grip strength predicts postoperative loss of independence in older adults undergoing hepatobiliary-pancreatic surgery.

Most influential comprehensive geriatric assessment factors on geriatricians' advice for cancer treatment in older adults.

Manual dexterity can be assessed using the Purdue Pegboard test (PPT) and used for staging of hand-arm vibration (HAV) syndrome. To describe PPT results among HAV-exposed workers and investigate what factors influence the results. We recruited workers from companies and an occupational medicine clinic in Sweden. They responded to a survey, underwent neurosensory testing and completed the PPT. The study recruited 225 workers with a mean (SD) HAV exposure duration of 16.7 (13.4) years. The mean (SD) result of the PPT was 12.8 (2.1) pins for the dominant hand, 12.7 (1.9) pins for the non-dominant hand and 10.6 (1.9) pins for both hands. Older age was consistently associated with poorer results (P < 0.001). Male sex was associated with lower scores for the dominant hand (P = 0.020) but not the non-dominant hand (P = 0.269) or both hands (P = 0.218). Current smoking was associated with poorer results for the dominant hand (P = 0.003) and both hands (P = 0.025), but not the non-dominant hand (P = 0.803). Self-reported reduced manual dexterity was associated with lower scores for the dominant hand (P < 0.001) and both hands (P < 0.001) but not the non-dominant hand (P = 0.070). Reduced two-point discrimination was consistently associated with poorer PPT results (P < 0.001). Low grip strength was associated with lower scores for the non-dominant hand (P = 0.008) and both hands (P = 0.025), but not the dominant hand (P = 0.310). Researchers noted lower scores on the PPT among older workers, men and smokers. Self-reported reduced manual dexterity, reduced two-point discrimination and low grip strength were also associated with poorer results.

Adverse muscle composition (AMC), defined by low muscle volume and increased muscle fat infiltration, has been associated with comorbidity and poor function in chronic kidney disease (CKD), and increased mortality in metabolic disorders and the general population. We investigated whether MRI-derived muscle composition is associated with all-cause mortality in a UK Biobank (UKB) imaging study among participants with CKD. UKB participants with CKD (eGFRCystatinC<60 ml/min/1.73m2) were identified. Thigh fat-free muscle volume and muscle fat infiltration (MFI) were quantified using MRI and AMRA® Researcher. Muscle volume was expressed as a sex- and BMI (body mass index)-invariant z-score. AMC was defined as the coexistence of low muscle volume (z-score <25th percentile, <-0.68 SD) and high MFI (>75th percentile; >7.69% in men and >8.82% in women), based on published UKB imaging thresholds. The mortality data were obtained through the UKB's linkage to national death registries. All-cause mortality was investigated using Kaplan-Meier curves and Cox-regression. Models were adjusted for sex, age, BMI, proteinuria, low hand grip strength, physical activity, smoking, alcohol, previous diagnosis of cancer, prevalent cardiovascular heart diseases, and type 2 diabetes. A total of 894 participants with CKD and available mortality data were included (52.5% male, mean±SD age 72.2±5.8 years, BMI 29±5.3 kg/m2, eGFR 53.5±6.4 ml/min/1,73m2). Prevalence of AMC was 32.3%. During a mean follow-up of 3.6 years, 50 participants died. AMC was significantly associated with higher all-cause mortality compared with normal muscle composition in unadjusted analyses [hazard ratio (HR) 6.17, 95% CI 2.36-16.15, p<0.001] and remained significant after adjustment for demographic, lifestyle factors, proteinuria, and clinical factors (HR 4.21, 95% CI 1.49-11.84; p=0.007). AMC is associated with greater risk of all-cause mortality in participants with CKD, identifying a high-risk population. Preservation of muscle composition may represent an important therapeutic consideration and potential target for future interventions in CKD management.

Blood-based biomarkers are increasingly used to characterize Alzheimer's disease (AD)-related pathology, yet substantial heterogeneity exists in how biomarker burden relates to cognitive performance. Grip strength, a marker of frailty and functional reserve, may modify this relationship. We conducted a cross-sectional analysis of 348 participants from the Aging Adult Brain Connectome (AABC) study. Global cognition was assessed using the Preclinical Alzheimer Cognitive Composite (PACC). Plasma biomarkers included phosphorylated tau-217 (pTau217), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and total tau (tTau). Multiple linear regression models tested biomarker × grip strength interactions, adjusting for demographic factors, APOE ε4 status, cardiometabolic risk factors, body mass index, and creatinine. Sensitivity analyses included age-based propensity score matching and age-stratified models. Participants with low PACC were older, had lower grip strength, and higher plasma biomarker levels than those with normal cognition (all p < 0.001). In adjusted models, significant interactions between low grip strength and biomarkers were observed for pTau217 (β = - 0.046, p < 0.01), NfL (β = - 0.002, p < 0.001), and GFAP (β = - 0.005, p < 0.05). Age-matched showed attenuation of some interaction effects except for low grip strength and NfL. Age-stratified analyses showed a significant interaction for NfL among adults ≥ 65years and for GFAP among those < 65years. Grip strength moderated the association between plasma AD-related biomarkers and cognitive performance, supporting physical strength as an indicator of vulnerability. Integrating simple strength measures with blood biomarkers may improve cognitive risk stratification in community-dwelling adults.

Grip strength (GS) is a potent biomarker in cardiovascular disease (CVD). However, evidence is scarce regarding the long-term dynamic changes of GS and their multifactorial determinants. This study aimed to identify distinct GS trajectories and their determinants among middle-aged and older Chinese adults with CVD. We analyzed data from 2,189 patients with CVD across three waves (2011, 2013, 2015) of the China Health and Retirement Longitudinal Study (CHARLS). GS was measured using a standardized protocol. Sex-stratified group-based trajectory model (GBTM) was employed to identify distinct GS trajectories. Multinomial logistic regression was performed to identify factors associated with trajectory group membership using the high-level GS trajectory as the reference group. GBTM identified three distinct parallel declining GS trajectories for each sex, classified as low-, middle-, and high-level GS groups. In fully adjusted models, older age, lower BMI, and higher FI were significantly associated with membership in both low- and middle-level GS groups compared to the high-level GS group for both sexes (all P < 0.05). This study revealed three GS trajectories among patients with CVD, with older age, lower BMI, and higher FI emerging as robust determinants of the low GS trajectory. These findings highlight the potential value of longitudinal GS monitoring for identifying high-risk individuals. Whether interventions targeting modifiable factors such as nutritional status and frailty can influence GS trajectories and subsequent clinical outcomes warrants further investigation.

With prolonged waiting times for deceased-donor kidney transplantation (DDKT) in Japan, objective data on frailty among wait-listed patients are limited. We assessed frailty using body composition and nutritional measures to identify predictors of 1year mortality or hospitalization. We retrospectively analyzed 134 patients on the DDKT waiting list starting December 2023. Body composition was assessed using multifrequency bioelectrical impedance analysis. Nutritional indices, including Survival Index, Prognostic Nutritional Index, Geriatric Nutritional Risk Index, and Nutrition Risk Index for Japanese Hemodialysis Patients, were calculated. Handgrip strength was also measured. Death or hospitalization within 1year was defined as an event. Random forest and SHapley Additive Explanation analyses were used to identify predictors of event occurrence. Among 134 patients (median age 58years, 68% male), 40% had obesity, 24% had sarcopenia, and nearly 50% exhibited malnutrition. The median dialysis duration was 10years. During 1year, 34 events (25%) occurred: seven deaths and 27 hospitalizations secondary to infection, malignancy, or heart failure. The fat mass index/fat-free mass index (FMI/FFMI) ratio was the strongest event predictor, followed by low grip strength, reduced SMI, low Survival Index, and low phase angle. Age, comorbidity index, and several nutritional indices showed limited predictive contributions. A significant number of Japanese DDKT candidates demonstrated frailty characterized by obesity, sarcopenia, and malnutrition. Objective indicators, particularly FMI/FFMI, may aid in evaluating vulnerability and eligibility during registration and renewal. Integrating these measures into standardized national criteria may improve equity and outcomes in DDKT candidate selection.

Hypertensive disorders of pregnancy (HDP) are leading causes of maternal and fetal morbidity and mortality. Although lower grip strength has been linked to higher cardiovascular risk in the general population, evidence on its relationship with HDP remains limited. We aimed to prospectively investigate this association in a large cohort of pregnant women. Between March 2017 and January 2020, 6802 pregnant women (mean age ± standard deviation: 26.6 ± 3.7 years) enrolled in the Tongji-Huaxi-Shuangliu Birth Cohort were included in this analysis. Grip strength was measured in early pregnancy (mean gestational week ± standard deviation: 10.3 ± 2.0 weeks) and assessed in three ways: absolute grip strength (AGS) and two relative indices (AGS normalized to body mass index or body weight). Logistic regression models were used to assess the associations between grip strength and the risk of HDP (gestational hypertension or preeclampsia). Multiple metabolic biomarkers (blood lipids, leptin, adiponectin, C-reactive protein, C-peptide, glycated hemoglobin, and homeostatic model assessment of insulin resistance) were measured among 638 women at enrollment. A total of 180 women developed HDP during pregnancy. The adjusted odds ratios (95% confidence intervals) of HDP across increasing quartiles of AGS in early pregnancy were 1.00 (reference), 0.93 (0.63-1.35), 0.67 (0.44-1.00), and 0.35 (0.21-0.56). Odds ratios across quartiles of two relative grip strength (RGS) indices showed similar patterns. Restricted cubic spline analyses indicated a nonlinear association between AGS and HDP risk (P for nonlinearity = 0.014). The risk plateaued at lower AGS levels but showed a linear inverse association above a threshold of 18.1 kg. In contrast, the two relative measures showed linear associations with HDP risk (P for nonlinearity ≥0.164). Additionally, higher RGS was generally correlated with favorable metabolic profiles (e.g., lower levels of low-density lipoprotein cholesterol, triglycerides, and C-reactive protein). Grip strength in early pregnancy was inversely associated with the risk of HDP, and RGS may serve as a simple and useful measure for risk stratification.

Health of people with obesity is a global concern. We developed an explainable sequential deep learning model using nationally representative physical fitness data to predict people with obesity and to identify the most influential predictors. We analyzed data from 204,334 adults collected between 2010 and 2023. A sequential neural network model was trained and evaluated using stratified 5-fold cross-validation. Model performance was assessed using accuracy, precision, recall, F1-score, and ROC-AUC, as well as MAE, MSE, and R². Explainability was examined using SHAP and LIME analyses to rank feature importance and interpret decision patterns. Across five stratified folds, the model achieved an overall accuracy of 0.87-0.88 (p < 0.001 vs. random). Fold 4 showed optimal performance (TN = 1,462; FN = 184; FP = 249; TP = 1,554), yielding an accuracy of 0.873 (precision = 0.866, recall = 0.855, F1 = 0.876, ROC-AUC = 0.95) and stabilizing at 20 epochs. For this model, MAE was 0.122, MSE was 0.041, and R² was 0.833, with an average prediction error of 0.171 for the first 50 samples. SHAP identified 20-m shuttle run estimated VO₂max (importance = 0.339), gender (0.2481), and relative grip strength (0.135) as the top predictors. LIME (intercept = 0.511, predicted=0.668, R² = 0.995) indicated that low estimated VO₂max ( < 28.71 ml/kg/min) and low relative grip strength ( < 38.17%) substantially increased the probability of obesity classification, particularly among females. This explainable sequential deep learning model accurately predicts people with obesity using physical fitness variables and highlights the critical role of cardiorespiratory fitness in obesity risk assessment and management.

Objectives: This study derives a composite frailty index for adults aged 50 and above in India, examines the distribution of frailty conditions across socioeconomic and demographic strata, and estimates the independent effects of background characteristics on frailty using multivariate analysis. Study Design: Cross-sectional secondary analysis of a nationally representative household survey. The cross-sectional design provides a baseline prevalence estimate but does not permit causal inference; findings should be interpreted accordingly. Place and Duration of Study: Six states of India (Assam, Karnataka, Maharashtra, Rajasthan, Uttar Pradesh, and West Bengal), using WHO Study on Global Ageing and Adult Health (SAGE) India Wave 1, 2007. These six states were selected by WHO-SAGE to represent India's geographic, linguistic, and socioeconomic diversity, though they do not constitute a nationally representative sample in the strict probability sense. Methodology: Data from 6,560 respondents aged 50 and above were analysed. A modified frailty index comprising seven deficit indicators — low grip strength, slowness, low body mass index, low physical activity, cognitive limitation, psychological limitation, and exhaustion — was constructed. This index adapts the Fried phenotype to SAGE India's measurement instruments; key differences from the standard Fried criteria are explicitly acknowledged in the methodology. Participants were classified as robust (0 deficits), pre-frail (1–2), intermediate frail (3–4), or frail (5–7). Multinomial logistic regression was used to estimate socioeconomic determinants of frailty. Results: Frailty prevalence was 15.5% overall, rising sharply with age from 7.1% in the 50–59 group to 50.8% in those aged 80 and above. Female sex, no formal education, low wealth, rural residence, and scheduled caste/tribe status were consistently associated with higher frailty burden. Multinomial logistic regression confirmed that advanced age, low education, and low wealth quintile were the strongest predictors of frailty, with statistically significant odds ratios at p &lt; 0.01. Conclusion: Frailty is prevalent and strongly socially patterned among older Indians. These findings call for the integration of frailty screening into India's primary healthcare infrastructure, and for targeted nutritional and physical rehabilitation programmes directed at low-income, low-education older adults in rural settings. Targeted preventive strategies addressing nutritional deficiency, physical deconditioning, and socioeconomic disadvantage are urgently needed to mitigate the growing burden of frailty in India's ageing population.

Depressive symptoms represent a major public health concern among middle-aged and older adults. Grip strength, a key indicator of physical frailty and biological ageing, and sleep disturbance, a recognised precursor of depression, have been independently linked to mental health outcomes. However, their combined effect on depressive symptoms remains unexplored. This study aimed to examine the association between grip strength levels, sleep status and their combined effects on the risk of depressive symptoms in middle-aged and older adults. This prospective cohort study included 16,395 participants from the Survey of Health, Ageing and Retirement in Europe, followed from 2006 to 2017. Logistic regression and generalised estimating equations were used to examine associations. During follow-up, 5241 participants (31.97%) developed depressive symptoms, with higher incidence in females (58.98%). After adjusting for covariates, both low grip strength (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.02-1.23) and sleep disturbance (OR 1.66, 95% CI 1.50-1.84) were independently associated with elevated risk of depressive symptoms. A synergistic effect was observed: individuals with both low grip strength and sleep disturbance had 1.87 times higher risk (95% CI 1.60-2.17) compared to those with high grip strength and no sleep disturbance. Sex- and agestratified analyses revealed stronger associations in males and older adults (≥70 years). Low grip strength and sleep disturbance are independently and synergistically associated with risk of depressive symptoms. Screening for both factors may help identify high-risk individuals for targeted preventive interventions.

Sarcopenia and Risk of Cardiovascular Events and Mortality: A Meta-analysis of Longitudinal Observational Studies.

Dynapenia-loss of muscle strength despite preserved muscle mass-is a clinical concern linked to functional decline in older adults. Diabetes may contribute to dynapenia; however, few studies have examined whether this association varies by sex and age. Clarifying these differences may help inform targeted prevention strategies. This study investigated the association between diabetes and dynapenia in community-dwelling older adults in Japan, focusing on sex- and age-specific differences. We conducted a cross-sectional analysis using pooled data from four geriatric cohorts in Japan. Participants were classified into three groups: (1) established diabetes (treatment or HbA1c ≥ 6.5%), (2) prediabetes (HbA1c 5.7%-6.4%, no treatment), and (3) non-diabetes (HbA1c < 5.7%, no treatment). Dynapenia was defined per Asian Working Group for Sarcopenia 2019 cutoffs as low grip strength with preserved muscle mass. Sex-stratified logistic regression examined the association between diabetes status and dynapenia, adjusting for age, body fat, comorbidities, lifestyle factors, and cohort. Analyses were also stratified by age group (65-74 and ≥ 75 years). Among 3085 participants (34.8% men; median age: 70 years), the prevalence of dynapenia was 13.0% in both sexes. In women, dynapenia prevalence increased with glycemic status; adjusted ORs were 1.32 (95% CI: 0.97-1.78) for prediabetes and 1.86 (1.27-2.71) for established diabetes. Stratified analyses showed significant associations in men aged 65-74 and women aged ≥ 75. Diabetes was associated with dynapenia, with distinct patterns by sex and age. Targeted strategies may be needed for younger-old men and older-old women with diabetes.

Older adults with cancer have a higher risk of developing sarcopenia, which may contribute to a worse prognosis. This study aimed to verify if sarcopenia predicts early death in older adults with cancer at the time of admission for outpatient treatment. This prospective cohort study was based on secondary data analysis from individuals over 60years old with cancer admitted to an oncogeriatric outpatient clinic from 2016 to 2020. Upon admission, sociodemographic data, clinical variables, nutritional, and physical assessment were evaluated. We considered probable sarcopenia (low hand grip strength [HGS], < 16kg women and<27kg men), sarcopenia (low HGS and calf circumference [CC]<31cm), and severe sarcopenia (low HGS, decreased CC, and timed up and go test ≥20s). The primary outcome was all-cause early death within 180days from outpatient evaluation. A multivariate analysis using the Cox proportional hazards model was performed, and the survival curve was established according to the degrees of sarcopenia. Of the 403 individuals included, 44.2% (n=178) had some degree of sarcopenia upon admission (25.1% had probable sarcopenia and 15.6% had sarcopenia). Eighty-seven (21.6%) individuals died within 180days. All degrees of sarcopenia were associated with death; probable sarcopenia (hazard ratio [HR] 1.76; confidence interval of 95% [95% CI] 1.05 to 2.99; p=0.03), sarcopenia (HR 2.00; 95% CI 1.11 to 3.62; p=0.02), and severe sarcopenia (HR 3.15; 95% CI 1.35 to 7.32; p=0.007). Low HGS was the only criterion for diagnosing sarcopenia associated with early death. The other risk factors associated with death were male sex, primary site of cancer, metastatic disease, reduced functionality, and polypharmacy. Identifying predictors of early death in older adults with cancer is clinically relevant and has a direct impact on therapeutic decision-making processes.

BackgroundMuscle loss is associated with chronic systemic inflammation and metabolic stress in the context of inflammatory bowel disease (IBD). However, studies that assessed the population-level effects of treated IBD on muscle health are limited.MethodsIn this study, pooled National Health and Nutrition Examination Survey 2011-2014 data of adults aged 20-59 years were analyzed through dual-energy X-ray absorptiometry and grip strength measurements. The treated IBD status was determined using prescription medication records, prioritizing specificity to capture individuals with clinically treated diseases rather than all IBD cases. Survey-weighted regression models were used to assess the associations with grip strength, appendicular lean mass index (ALMI), and muscle quality, including an IBD × age interaction.ResultsAmong 5,522 adults, 25 were treated with IBD, requiring careful interpretation due to the limited effective sample size. IBD was associated with significantly lower grip strength and reduced ALMI after adjusting for age, sex, and body mass index. A significant interaction indicated a steeper age-related decline in grip strength among adults with IBD. No significant differences in muscle quality were observed between the groups.ConclusionMuscle loss in patients with treated IBD was related to reduced lean body mass and a pattern consistent with faster age-related neuromuscular loss. These findings highlight an opportunity for the early identification of functional vulnerability using continuous muscle phenotypes and emphasize the potential role of modifiable lifestyle interventions, including physical activity, resistance training, and nutritional optimization, in preserving muscle health and improving long-term functional decline in adults with IBD.

Empty-nest older adults are considered a high-risk group for frailty due to constrained social support systems, yet the heterogeneity in their frailty progression remains poorly characterized. This study aimed to identify distinct frailty trajectory classes among Chinese empty-nest older adults and explore class-specific predictive factors. We analyzed eight years of data from the China Health and Retirement Longitudinal Study. The analysis included 1399 empty-nest older adults after eligibility screening. Frailty was assessed by the frailty index (FI). Growth Mixture Modeling was employed to identify FI trajectory classes, an linear, quadratic, and freely estimated forms were compared. Variable selection was performed via LASSO regression with bootstrap stability verification. Final predictors were analyzed using multinomial logistic regression. A three-class quadratic model best represented the FI trajectories: "Low-increasing", "High-fluctuating", and "Elevated-stable". Common risk factors included older age, rural residence, lower grip strength, death of children, and lower life satisfaction. The "High-fluctuating" trajectory was associated with poorer childhood health and smoking. The "Elevated-stable" trajectory was predicted by worklessness and by drinking. Physiological indicators showed no independent associations. Frailty among Chinese empty-nest older adults follows heterogeneous pathways shaped by life-course, socioeconomic, and psychophysiological factors. These results support the need for trajectory-specific screening, early risk detection, and tailored interventions for high-risk subgroups.

Hip fractures are the most serious osteoporotic fractures, and patients often develop contralateral hip fractures. Various factors are reported as risks for secondary hip fracture, but risk analysis is not yet standardized. We conducted a longitudinal prospective observational study of 1395 hip fracture patients followed for 345.2 ± 189.3 (3–795) days to identify risk factors for secondary hip fracture. Of the initial 1395 patients, we followed 1223 cases, excluding those who already had a contralateral hip fracture at time of enrollment. Univariate analysis using the log-rank test and Cox regression analysis of 51 factors such as age, BMI and living alone in relation to secondary hip fracture showed that four factors, namely, living alone, low grip strength (<18 kg), three or more existing vertebral fractures and hypertension, were significant risks for secondary fracture. Multivariate Cox regression analysis using factors identified as significant risks for secondary fracture in univariate analysis confirmed that living alone and the presence of three or more existing vertebral fractures could be useful in predicting risk for secondary hip fracture. Our results may provide important knowledge to prevent contralateral secondary hip fractures in patients after the first fracture.

Background: Few studies have examined changes in diet quality into old age, and related these changes to musculoskeletal outcomes. We examined this among Hertfordshire Cohort Study participants. Methods: In total, 178 individuals provided diet quality scores derived in 1998-2004, 2011 and 2017 (median age 64.0, 74.7 and 80.7) using principal component analysis of food frequency questionnaires; higher scores indicated healthier diets (more fruit and vegetables, oily fish and wholemeal bread, and less white bread, added sugar, full-fat dairy products, chips and processed meat). Pearson correlations between diet quality scores at each time-point were computed. Group-based trajectory modelling of diet quality scores was implemented; trajectory groups as predictors of musculoskeletal outcomes (history of hip/knee replacement, osteoporosis, fall in previous year, low grip strength, low gait speed) in 2017 were examined using logistic regression with age and sex included as covariates. Results: Diet quality showed moderate stability over time (0.64 < r < 0.74). Three trajectory groups were identified: low (29%), medium (51%), and high diet quality (20%). A higher diet quality group was related to greater odds (95% CI) of hip/knee replacement (1.85 (1.05, 3.26) per higher category); associations with other musculoskeletal outcomes were weak (p > 0.17). Conclusions: Weak associations were observed between diet quality trajectories and musculoskeletal outcomes. However, higher diet quality was related to increased likelihood of hip/knee joint replacement, potentially due to confounding by socioeconomic position. The stability of diet quality suggests individuals with poorer diets around age 65 are likely to maintain these patterns into old age and may benefit from targeted interventions.

IntroductionFrailty leads to disability, morbidity, and mortality in older persons. The Fried’s Frailty Phenotype (FFP), derived in the American Cardiovascular Health Study (CHS), is widely used around the world to define frailty, but lacks adaptation in African populations.ObjectiveTo derive a modified FFP definition which best identifies frailty in a Southern African context.MethodsA population-based cross-sectional study of adults aged ≥40 years collected data from questionnaires and physical assessments. Original CHS, population-dependent, European Working Group on Sarcopenia in Older People2 (EWGSOP2) and Sarcopenia Definitions and Outcomes Consortium (SDOC) and independent thresholds were all applied to the five FFP criteria (weight loss, exhaustion, low physical activity [PA], low grip strength [GS] and slow walking speed [WS]) to assess non-differentiality, internal consistency, and plausibility.ResultsThe 919 participants had a median age of 59 years [IQR 50–70], 53.3% were female. Self-reported exhaustion was reported by 37.5%nd self-reported weight loss by 34.9%. Using the lowest quintile of body mass index (BMI), missed 15.2% of overweight and obese participants who reported weight loss. Using CHS thresholds, low PA was present in 36.7%. Grip strength correlated better with age (r = −0.45) than BMI (r = −0.19). Therefore, the sex-specific tenth percentile of the 40–49-years-age band of the study population was used rather than the CHS approach. The modified SDOC threshold identified slow WS in almost all (85.8%) and was therefore non-differential. The EWGSOP2 and CHS thresholds identified slow WS in 52.9% and 22.9%, respectively, compared to 34.5% using the study population’s lowest quintile.ConclusionCulture and language sensitive questions for self-reported exhaustion and weight loss, CHS thresholds for low PA, and population dependent thresholds for GS and WS were the most suitable modifications in a Southern African setting, highlighting the need for region-specific adaptations when diagnosing frailty.

ABSTRACTSarcopenia is a significant public health concern that adversely affects the health and quality of life of older adults. The causal and longitudinal relationships between homocysteine (Hcy), B vitamins, and sarcopenia remain unclear. This study integrated genetic evidence with clinical cohort data to investigate these associations using a two‐stage design. First, we performed a two‐sample Mendelian randomization (MR) analysis using summary data from large‐scale genome‐wide association studies (GWAS) of European ancestry. We examined the potential causal effects of Hcy, Vit B6, folate, and Vit B12 on sarcopenia‐related phenotypes, including appendicular lean mass (ALM), grip strength, and walking pace, using the inverse‐variance weighted (IVW) method as the primary analysis. Second, to validate these genetic findings and examine their longitudinal relevance, we established an independent retrospective clinical cohort of 1322 individuals. Group‐based trajectory modeling identified distinct Hcy trajectory groups, and multivariable Cox regression with restricted cubic splines was used to assess longitudinal associations and dose–response relationships with incident sarcopenia. The MR analysis showed that genetically predicted higher Hcy levels were causally associated with low grip strength (OR = 1.133, 95% CI: 1.016–1.263, p = 0.025) and lower ALM (β = −0.043, 95% CI: −0.069 – −0.016, p = 0.001). In the clinical cohort, individuals in the medium‐stable and high‐stable Hcy trajectory groups had a 1.965‐fold (95% CI: 1.027–3.759) and 2.832‐fold (95% CI: 1.608–4.987) higher risk of developing sarcopenia, respectively, compared to the low‐stable group. A continuous, incremental dose–response relationship was observed between baseline Hcy levels and sarcopenia risk (p < 0.05). No robust genetic evidence supported causal roles for B vitamins in sarcopenia. This study provides evidence that Hcy is associated with sarcopenia risk, suggesting that interventions targeting Hcy may help prevent or delay sarcopenia onset.