Diagnostic test accuracy of serum creatinine and cystatin C-based index for sarcopenia: a systematic review and meta-analysis.

BACKGROUND: Sarcopenia is an important prognostic factor, but its optimal screening methods remain challenging. Several new indices developed based on serum creatinine (Cr) and cystatin C (CysC) have been proposed to be diagnostic biomarkers for sarcopenia screening. OBJECTIVE: This review aimed to evaluate the diagnostic accuracy of serum Cr- and CysC-based indices for sarcopenia diagnosis. METHODS: We systematically searched MEDLINE, EMBASE, SCIE and SCOPUS from inception to 2 April 2023. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate random-effects model was used to synthesise the pooled sensitivity, specificity and area under the curves of the summary receiver operating characteristic (SROC-AUC). RESULTS: We retrieved 936 publications and included 16 studies with 5,566 participants (mean age ranged: 51.0-78.4 years, 50.2% men). The prevalence of sarcopenia ranged from 7.8 to 69.5%. All included studies presented a moderate to high risk of bias. The serum Cr- and CysC-based indices showed moderate diagnostic accuracy for sarcopenia (pooled sensitivity: 0.67, 95% CI 0.57-0.75; pooled specificity: 076, 95% CI 0.67-0.83; pooled SROC-AUC: 0.78, 95% CI 0.74-0.81). The Cr/CysC ratio is the most widely studied index, followed by the Cr × eGFRcys index. Overall, both indicators had satisfactory and comparable performance in screening sarcopenia. CONCLUSION: Serum Cr- and CysC-based indices showed moderate diagnostic accuracy for sarcopenia. The most studied indices-the Cr/CysC ratio and Cr × eGFRcys index-had comparable diagnostic accuracy for evaluating sarcopenia and may serve as surrogate markers for sarcopenia. However, further validation is required to verify these findings.

Creatinine-to-cystatin C ratio and frailty in older adults: a longitudinal cohort study.

BACKGROUND: Creatinine-to-cystatin C ratio (CCR) has been associated with multiple adverse outcomes. However, little is known about its relationship with frailty. We aimed to explore the association between CCR and frailty among older adults. METHODS: A total of 2599 participants aged ≥ 60 years (mean age 67.9 ± 6.0 years, 50.4% males) were included from the China Health and Retirement Longitudinal Study (2011-2015). Baseline CCR was calculated as plasma creatinine (mg/dL) / cystatin C (mg/L) × 10 and was grouped by quartiles. Frailty was evaluated by the validated physical frailty phenotype (PFP) scale and was defined as PFP score ≥ 3. The generalized estimating equations model was used to explore the relationship between CCR and frailty. RESULTS: The frailty risk decreased gradually with increasing CCR in the quartiles (P for trend = 0.002), and the fourth CCR quartile was associated with a significantly lower risk of frailty compared with the lowest quartile (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.19-0.70). When modeling as a continuous variable, per 1-unit increase in CCR was related to 17% decreased odds of frailty (OR 0.83, 95% CI 0.74-0.93). The association was consistent in male and female participants (P for interaction = 0.41). Poisson models revealed that frailty score was negatively associated with CCR (ß= -0.11, 95% CI= -0.19 to -0.04), and sex did not significantly moderate the associations (P for interaction = 0.22). The results were not affected by further adjusting for high-sensitivity C-reactive protein. Similar results were observed by analyses with multiple imputation technique and analyses excluding participants with baseline frailty. CONCLUSIONS: Higher CCR was associated with a lower frailty risk. CCR may be a simple marker for predicting frailty in older adults.

The geriatric nutrition risk index is longitudinally associated with incident Sarcopenia: evidence from a 5-year prospective cohort.

BACKGROUND: Previous studies investigating the association between the geriatric nutrition risk index (GNRI) and sarcopenia either lacked longitudinal evidence or narrowly focused on specific populations. AIMS: We aimed to reveal longitudinal associations of GNRI with sarcopenia risk in community-dwelling Chinese. We also investigated interaction effects of potential factors on such associations. METHODS: We included participants aged ≥ 50 years with sufficient data from the WCHAT study who did not have sarcopenia at baseline and completed sarcopenia assessment during follow-up. GNRI was calculated according to the formula based on serum albumin, height and weight. Sarcopenia was diagnosed according to the 2019 AWGS consensus. Longitudinal associations between GNRI and sarcopenia were estimated by logistic regression with GNRI as either a continuous or categorical variable by tertiles, using generalized estimating equations (GEE) as sensitivity analyses. Subgroup analyses by potential covariates were conducted to detect interaction effects. RESULTS: A total of 1907 participants without baseline sarcopenia were finally included, of whom 327 (17.1%) developed incident sarcopenia during 5-year follow-up. After controlling for confounders, sarcopenia risk decreased with each one standard deviation increase in GNRI (ORadjusted=0.36, 95% CI 0.31-0.43), and it also decreased successively from the lowest (< 111.2) through middle (111.2-117.7) to the highest (≥ 117.8) tertile of the GNRI level (P for trend < 0.001). Similar results were yielded by GEE. Such associations generally remained robust across subgroups with distinct characteristics, while significant differences were observed between different age groups (≥ 65 vs. <65 years) (interaction P-value < 0.05). CONCLUSION: GNRI is longitudinally associated with sarcopenia risk with possibly age-specific differences in association magnitude, which holds implications for policymakers to conduct population-based risk assessment.

Is waist-calf circumference ratio associated with frailty in older adults? Findings from a cohort study.

BACKGROUND: The waist-calf circumference ratio (WCR) has been suggested as a potential indicator of visceral adiposity. Nevertheless, the relationship between WCR and the risk of frailty remains unclear. Therefore, our study aimed to investigate the association between WCR and longitudinal changes in WCR with frailty risk in older adults. METHODS: We included 2359 participants aged ≥ 65 years without frailty (frailty index [FI] ≤ 0.21) from the Chinese Longitudinal Healthy Longevity Survey in the 2014 wave. The follow-up was conducted in 2018. We investigated the relationship of WCR, waist circumference (WC), and calf circumference (CC) with frailty using both the Cox proportional hazards model and the generalized estimating equation (GEE). RESULTS: During a median follow-up of 4.0 years, 668 (28.2%) frailty occurred. Those with higher WCR and WC had a significantly increased risk of frailty (fifth quintile compared with first quintile: hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.24-2.04 for WCR; HR = 1.69, 95% CI 1.27-2.24 for WC), whereas those in the fourth quintile of CC had a lower likelihood of developing frailty compared to those in the first quintile (HR = 0.67, 95% CI 0.50-0.89). Interaction analyses showed that the effects of WCR on frailty were more pronounced in females (P-interaction = 0.016). GEE analyses revealed that increased WCR and WC were associated with a higher risk of frailty (odds ratio [OR] = 1.74, 95% CI 1.43-2.12 for WCR; OR = 1.03, 95% CI 1.02-1.04 for WC), while CC showed opposite results (OR = 0.95, 95% CI 0.93-0.97). CONCLUSIONS: A higher WCR and WC, as well as a lower CC, were significantly associated with higher frailty. Of these measures, WCR demonstrated the strongest association with frailty, suggesting that having a combination of high central fat and low lean body mass may increase the risk of developing frailty.

Prevalence and prognostic value of preexisting sarcopenia in patients with mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: Sarcopenia is defined as age-related loss of muscle mass, strength, and/or function in the context of aging. Mechanical ventilation (MV) is one of the most frequently used critical care technologies in critically ill patients. The prevalence of preexisting sarcopenia and the clinical impact of its prognostic value on patients with MV are unclear. This review sought to identify the prevalence and prognostic value of preexisting sarcopenia on MV patient health outcomes. METHODS: Relevant studies were identified by searching MEDLINE, Embase, and the Cochrane library and were searched for all articles published as of December 2021. The prevalence of sarcopenia was determined using the authors' definitions from the original studies. Comparisons were made between patients who did and did not have sarcopenia for prognostic outcomes, including mortality, the number of days of MV, the length of intensive care unit stay, and the length of hospital stay. Odds ratios (ORs) and weighted mean differences with 95% confidence intervals (CIs) were used for pooled analyses of the relationships between sarcopenia and prognostic outcomes. RESULTS: The initial search identified 1333 studies, 17 of which met the eligibility criteria for the quantitative analysis, including 3582 patients. The pooled prevalence was 43.0% (95% CI 34.0-51.0%; I2 = 96.7%). The pooled analyses showed that sarcopenia was related to increased mortality (OR 2.13; 95% CI 1.70, 2.67; I2 = 45.0%), longer duration of MV (MD = 1.22; 95% CI 0.39, 2.05; I2 = 97.0%), longer days of ICU stay (MD = 1.31; 95% CI 0.43, 2.19; I2 = 97.0%), and hospital stay (MD 2.73; 95% CI 0.58, 4.88; I2 = 98.0%) in patients with MV. CONCLUSION: The prevalence of sarcopenia is relatively high in patients with MV, and it will have a negative impact on the prognosis of patients. However, further, large-scale, high-quality prospective cohort studies are required.

Association between stress hyperglycemia ratio and delirium in older hospitalized patients: a cohort study.

BACKGROUND: It remains unclear whether stress hyperglycemia is associated with delirium. We performed this cohort study to determine the association between stress hyperglycemia and delirium. METHODS: We consecutively enrolled patients aged ≥70 years who were admitted to the Geriatric Department of West China Hospital between March 2016 and July 2017. Stress hyperglycemia ratio (SHR) was calculated as fasting blood glucose divided by estimated average glucose derived from glycosylated hemoglobin (HbA1c) and was classified into three tertiles. Delirium was screened within 24 h of admission and three times daily thereafter, using the confusion assessment method. The Cox proportional hazards models were used to assess the association of SHR with delirium. RESULTS: Among 487 included patients (mean age 83.0 years, 72.0% male), 50 (10.3%) patients experienced delirium during hospitalization. Compared to the second tertile, both the lowest and the highest SHR tertiles were independently associated with delirium (hazard ratio [HR] 3.71, 95% confidence interval [CI] 1.45-9.51; and HR 2.97, 95% CI 1.29-6.81, respectively). Similar results were found after further adjusting for statin comedication. Multiple-adjusted restricted cubic splines revealed a nonlinear relationship between SHR and delirium (Pnonlinearity=0.04). Adding SHR to conventional risk factors improved the risk prediction of delirium (net reclassification index 0.39, P=0.01; integrated discrimination improvement 0.07, P=0.03). Subgroup analyses indicated that the relationship between SHR and delirium was more apparent in patients with HbA1c <6.5%, with significantly higher HR in the first (3.65, 95% CI 1.11-11.97) and third (3.13, 95% CI 1.13-8.72) SHR tertiles compared to the second tertile, while there was no significant association between SHR and delirium in those with HbA1c ≥6.5%. CONCLUSIONS: Both lower and higher SHR were associated with increased risk of delirium but only in patients with HbA1c <6.5%. Admission SHR may serve as a promising predictor of delirium, and incorporating this biomarker into prediction algorithms might have potential clinical utility in aiding delirium risk stratification, especially in those with HbA1c <6.5%.

Reliability and validity of two hand dynamometers when used by community-dwelling adults aged over 50 years.

BACKGROUND: The Jamar hydraulic dynamometer is a widely recognized tool for measuring grip strength. Nevertheless, the devices used most often in Asian countries are spring-type dynamometers, represented by the CAMRY dynamometer or Smedley dynamometer. We aimed to evaluate the reliability and validity of the CAMRY dynamometer compared with the Jamar dynamometer. METHODS: This was a cross-sectional study using a random crossover design in the grip strength test with two dynamometers. A total of 1064 healthy community-dwelling older adults aged 50-90 years old, which included 686 minorities and 378 Han Chinese, were recruited into the study from July to September 2021. We assessed the reliability and validity of the CAMRY EH101 dynamometer, and the Jamar dynamometer was regarded as the reference device. The order of testing with two dynamometers was randomized in a 1:1 ratio, with a 10-min gap between the two devices. Intraclass correlation coefficients (ICCs) and Bland-Altman analysis were calculated to assess reliability and validity between the two devices. RESULTS: The average handgrip strength (HGS) values at six times by the Jamar and CAMRY devices were 25.0 ± 7.9 kg and 24.6 ± 7.5 kg, respectively. The ICC values between the two devices were 0.815-0.854, and the systematic bias underestimated by the CAMRY dynamometer was 0.5 kg in men and 0.6 kg in women. We carried out a linear regression equation by sex, and their relationship was found as follows: male HGS (kg)Jamar = 8.001 + 0.765 × HGS (kg)CAMRY; female HGS (kg)Jamar = 3.681 + 0.840 × HGS (kg)CAMRY. CONCLUSIONS: The CAMRY EH101 dynamometer provides excellent reliability and validity. This device can serve as a reliable, inexpensive, and practical device to assess grip strength in geriatric clinical practice. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2100046367 ; Date of clinical trial reistration: 15/05/2021.

Higher cerebral small vessel disease burden is associated with smaller hematoma volume in mixed-location intracerebral hemorrhage.

OBJECTIVE: To study the relationship between cerebral small vessel disease (CSVD) and hematoma volume in mixed-location intracerebral hemorrhage (ICH), and non-mixed ICH (hypertensive arteriopathy/cerebral amyloid angiopathy-related ICH). METHODS: We consecutively collected patients with primary ICH with MRI. Mixed-location ICH was defined as having ICH or cerebral microbleeds (CMBs) in both lobar and deep regions. CSVD markers including lacunes, white matter hyperintensities (WMH), CMBs, and enlarged perivascular spaces (EPVS) were assessed on brain MRI during hospitalization. Multivariable binary logistic regression (≥30 ml vs. <30 ml) and linear regression analyses (log-transformed hematoma volume as dependent variable) were implemented to explore the association between CSVD and hematoma volume. RESULTS: Of the 167 included patients, 69 (41.3%) had mixed-location ICH, with higher prevalence of lacune, more CMB count, higher WMH score and total CSVD score than those with non-mixed ICH (all p < .001). Higher WMH score was associated with lower risk of hematoma volume ≥30 ml (adjusted OR 0.521, 95% CI 0.299-0.908, p = .021) in patients with mixed-location ICH. Also, multivariable linear regression showed the association of smaller hematoma volume with higher CSVD burden, especially in mixed-location ICH (ß = -0.349, p = .019 for CMB ≥ 5; ß = -0.183, p < .001 for WMH score; ß = -0.456, p = .002 for EPVS>20 in basal ganglia and/or centrum semiovale; ß = -0.256, p = .002 for CSVD score), while these relationships were not observed in non-mixed ICH. CONCLUSIONS: Higher CSVD burden is associated with smaller hematoma volume in mixed-location ICH, but not in non-mixed ICH, which is novel and needs further studies with larger sample size to confirm our results and explore the underlying mechanisms.

Association between non-high-density lipoprotein cholesterol and haemorrhagic transformation in patients with acute ischaemic stroke.

BACKGROUND: It is unclear whether non-high-density lipoprotein cholesterol (Non-HDL-C) is associated with haemorrhagic transformation (HT) after acute ischaemic stroke (AIS). We aimed to explore the association between Non-HDL-C and HT, as well as compare the predictive values of Non-HDL-C and low-density lipoprotein cholesterol (LDL-C) for HT. METHODS: We consecutively enrolled AIS patients within 7 days of stroke onset. Participants were divided into four categories according to quartiles of Non-HDL-C. HT was assessed by follow-up brain imaging. We assessed the association between Non-HDL-C, LDL-C and HT in multivariate logistic regression analysis. RESULTS: A total of 2043 patients were included, among whom 232 were identified as HT. Compared with the highest quartiles, the first, second and third quartiles of Non-HDL-C were associated with increased risk of HT (adjusted odds ratios [ORs] 1.74 [95% confidence interval [CI] 1.09-2.78], 2.01[95% CI 1.26-3.20], and 1.76 [95% CI 1.10-2.83], respectively, P for trend = 0.024). Similar results were found for LDL-C. There was significant interaction between Non-HDL-C and age (P for interaction = 0.021). The addition of Non-HDL-C and LDL-C to conventional factors significantly improved predictive values [Non-HDL-C, net reclassification index (NRI) 0.24, 95%CI 0.17-0.31, P < 0.001; LDL-C, NRI 0.15, 95%CI 0.08-0.22, P = 0.03]. CONCLUSIONS: Low Non-HDL-C was associated with increased risks of HT. In addition, Non-HDL-C has similar effects as LDL-C for predicting HT.

Lymphocyte-to-monocyte ratio and risk of hemorrhagic transformation in patients with acute ischemic stroke.

BACKGROUND: Hemorrhagic transformation (HT) is a common complication of acute ischemic stroke (AIS), and inflammation has been found to play an important role in the occurrence of HT. We aimed to investigate the impact of lymphocyte-to-monocyte ratio (LMR), a maker of inflammatory status, on HT in patients with AIS. METHODS: Consecutive AIS patients within 7 days from stroke onset were enrolled between January 2016 and October 2017. LMR was calculated according to lymphocyte and monocyte counts obtained within 24 h on admission. Patients were categorized into three groups according to LMR tertiles. HT was detected by follow-up computed tomography (CT) or magnetic resonance imaging (MRI) during hospitalization. The multivariate logistic analysis was used to evaluate the independent relationship between LMR and HT. RESULTS: A total of 1005 patients were finally included. HT was observed in 99 (9.9%) patients, with 51 (5.1%) hemorrhagic infarction (HI) and 48 (4.8%) parenchymal hematoma (PH). After adjustment for potential confounders, the odds ratio (OR) of HT was 0.523 (95% confidence interval [CI] 0.293-0.936, P = 0.029) for the highest LMR tertile compared with the lowest tertile. Multiple-adjusted spline regression model showed a nonlinear approximately L-shaped relationship between LMR levels and HT (P for nonlinear trend = 0.030). There was no significant association of baseline LMR with PH (OR 0.562, 95% CI 0.249-1.268, P = 0.165). CONCLUSION: Lower LMR was independently related to higher risk of HT in patients with AIS. Admission LMR may be used as one of the predictors for HT. Further prospective multicenter studies are needed to validate our findings.

External Validation and Modification of the EDEMA Score for Predicting Malignant Brain Edema After Acute Ischemic Stroke.

BACKGROUND: Accurate prediction of malignant brain edema (MBE) after stroke is paramount to facilitate close monitoring and timely surgical intervention. The Enhanced Detection of Edema in Malignant Anterior Circulation Stroke (EDEMA) score was useful to predict potentially lethal malignant edema in Western populations. We aimed to validate and modify it to achieve a better predictive value for MBE in Chinese patients. METHODS: Of ischemic stroke patients consecutively admitted in the Department of Neurology, West China Hospital between January 2010 and December 2017, we included patients with anterior circulation stroke, early signs of brain edema on computed tomography within 24 h of onset, and admission National Institutes of Health Stroke Scale (NIHSS) score ≥ 8. MBE was defined as the development of signs of herniation (including decrease in consciousness and/or anisocoria), accompanied by midline shift ≥ 5 mm on follow-up imaging. The EDEMA score consisted of five parameters: glucose, stroke history, reperfusion therapy, midline shift, and cistern effacement. We created a modified score by adding admission NIHSS score to the original EDEMA score. The discrimination of the score was assessed by the area under the receiver operating characteristics curve (AUC). Calibration was assessed by Hosmer-Lemeshow test and calibration plot. We compared the discrimination of the original and modified score by AUC, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Clinical usefulness of the two scores was compared by plotting net benefits at different threshold probabilities in the decision curve analysis. RESULTS: Of the 478 eligible patients (mean age 67.3 years; median NIHSS score 16), 93 (19%) developed MBE. The EDEMA score showed moderate discrimination (AUC 0.72, 95% confidence interval [CI] 0.67-0.76) and good calibration (Hosmer-Lemeshow test, P = 0.77). The modified score showed an improved discriminative ability (AUC 0.80, 95% CI 0.76-0.84, P < 0.001; NRI 0.67, 95% CI 0.55-0.78, P < 0.001; IDI 0.07, 95% CI 0.06-0.09, P < 0.001). Decision curves showed that the modified score had a higher net benefit than the original score in a range of threshold probabilities lower than 60%. CONCLUSIONS: The original EDEMA score showed an acceptable predictive value for MBE in Chinese patients. By adding the admission NIHSS score, the modified score allowed for a more accurate prediction and clinical usefulness. Further validation in large cohorts of different ethnicities is needed to confirm our findings.

Association of handgrip strength asymmetry and weakness with depression among middle-aged and older population in China: A cohort study.

BACKGROUND: Handgrip strength (HGS) weakness and asymmetry were recently reported to be associated with age-related health conditions. However, little is known about their combined effects on depression. We aimed to explore the joint association of HGS asymmetry and weakness with depressive symptoms in Chinese middle and older aged population. METHODS: 8700 participants aged ≥45 years were enrolled from China Health and Retirement Longitudinal Study (2015-2018). HGS weakness was determined as maximal HGS < 28 kg in males and <18 kg in females. HGS asymmetry was measured by HGS ratio and was defined using two different rules. Specifically, HGS ratio < 0.90 or >1.10 (10 % rule) and <0.80 or >1.20 (20 % rule) were considered as asymmetry. Participants were classified into four groups: normal and symmetric HGS, asymmetry only, weakness only, and both weakness and asymmetry. Depressive symptoms were assessed by the 10-item Center for Epidemiologic Studies Depression Scale, with scores ≥12 defined as depression. The logistic regression and multiple linear regression models were conducted to estimate the associations between HGS status and depressive symptoms. RESULTS: The three-year incidence of depression was 19.2 %. After adjusting for covariates, compared to normal and symmetric HGS, participants with both HGS asymmetry and weakness showed the greatest risk of incident depression (10 % rule: OR 1.55, 95 % CI 1.19-2.02; 20 % rule: OR 1.71, 95 % CI 1.16-2.50). The coexistence of asymmetry and weakness was related to a significant increase in depression score (10 % rule: ß 0.96, 95 % CI 0.38-1.54; 20 % rule: ß 0.94, 95 % CI 0.08-1.81). The complete case analysis supported the results, and the associations were not modified by age, sex, and hand dominance. LIMITATIONS: Depressive assessment was based on self-reported screening instrument. CONCLUSIONS: The presence of both HGS asymmetry and weakness was associated with a higher risk of depression. Examining HGS asymmetry along with weakness may aid in identifying individuals at risk of depression to enable early interventions.

Association of handgrip strength asymmetry and weakness with functional disability among middle-aged and older adults in China.

Background: Little is known about the association of handgrip strength (HGS) asymmetry with functional disability in China. We aimed to examine the individual and combined association of HGS asymmetry and weakness with functional disability among middle-aged and older Chinese adults. Methods: We included participants aged ≥45 years from two waves of the China Health and Retirement Longitudinal Study (2011 and 2015). HGS weakness was defined as the maximal HGS<28 kg for men and <18 kg for women. HGS asymmetry was measured by dividing the maximal nondominant HGS (kg) by the maximal dominant HGS (kg), with the value <0.90 or >1.10 considered as asymmetry. Functional disability was assessed by activities of daily living (ADL) and instrumental activities of daily living (IADL) and was defined as encountering difficulty in completing one or more ADL/IADL tasks. The logistic regression models were used to explore the association between HGS measures and functional disability. Results: 11 950 (mean age 59.2 ± 9.6 years, 47.9% males) and 7540 (mean age 57.5 ± 8.6 years, 50.1% males) participants were included in the cross-sectional and prospective study, respectively. HGS asymmetry and weakness, individually or simultaneously, were associated with an increased prevalence of functional disability. During the four-year follow-up, 1822 (24.2%) participants had incident functional disability. The separate exposure to HGS asymmetry (odds ratio (OR) = 1.18; 95% confidence interval (CI) = 1.05-1.32) or weakness (OR = 1.59; 95% CI = 1.30-1.95) was independently associated with functional disability. For combined associations, those with both weakness and asymmetry showed the greatest risk of new-onset functional disability (OR = 1.91; 95% CI = 1.45-2.52). Conclusions: HGS asymmetry and weakness were associated with a higher risk of functional disability. Assessing HGS asymmetry together with weakness may help to better identify those at risk of functional disability to enable early interventions.

Identification of nicotinamide N-methyltransferase as a promising therapeutic target for sarcopenia.

Sarcopenia is a significant geriatric syndrome that involves the loss of skeletal muscle mass and strength. Due to its substantial endocrine role, the metabolic microenvironment of skeletal muscle undergoes changes with age. Examining the pathogenesis of sarcopenia through focusing on metabolic dysregulation could offer insights for developing more effective intervention strategies. In this study, we analyzed the transcriptomics data to identify specific genes involved in the regulation of metabolism in skeletal muscle during the development of sarcopenia. Three machine learning algorithms were employed to screen key target genes exhibiting strong correlations with metabolism, which were further validated using RNA-sequencing data and publicly accessible datasets. Among them, the metabolic enzyme nicotinamide N-methyltransferase (NNMT) was elevated in sarcopenia, and predicted sarcopenia with an area under the curve exceeding 0.7, suggesting it as a potential therapeutic target for sarcopenia. As expected, inhibition of NNMT improved the grip strength in aging mice and alleviated age-related decline in the mass index of the quadriceps femoris muscles and whole-body lean mass index. Additionally, the NNMTi treatment increased the levels of nicotinamide adenine dinucleotide (NAD+) content, as well as PGC1α and p-AMPK expression in the muscles of both the D-galactose-treated mouse model and naturally aging mouse model. Overall, this work demonstrates NNMT as a promising target for preventing age-related decline in muscle mass and strength.

Longitudinal associations between social support and sarcopenia: findings from a 5-year cohort study in Chinese aged ≥50 years.

OBJECTIVES: We aimed to investigate longitudinal associations of overall social support and its sub-domains with risk of sarcopenia and its related traits in community-dwelling Chinese aged ≥ 50 years. We also explored interaction effects of potential factors on such associations. DESIGN: A prospective cohort study. SETTING: Community-based setting in western China. PARTICIPANTS: We included participants aged ≥50 years with complete information necessary for analysis from the WCHAT study who did not have sarcopenia at baseline (2018) and had sufficient data for sarcopenia assessment during 2021-2023. MEASUREMENTS: Exposures included overall social support, subjective support, objective support and support utilization, which were assessed with the Social Support Rating Scale. Outcomes included sarcopenia, low muscle mass (LMM), low muscle strength and low physical performance, which were diagnosed with the 2019 AWGS consensus. Longitudinal associations between the exposures and outcomes were estimated by logistic regression, with generalized estimating equations (GEE) as sensitivity analyses. Subgroup analyses by potential covariates were conducted to detect interaction effects. RESULTS: A total of 1905 participants were finally included in the analytic sample, of whom 326 (17.1%) developed incident sarcopenia during 5-year follow-up. After controlling for confounders, higher degree of overall social support (OR = 0.87, 95%CI 0.76-0.99), subjective support (OR = 0.88, 95%CI 0.77-0.99) and support utilization (OR = 0.87, 95%CI 0.77-0.99) correlated with lower sarcopenia risk, among which higher support utilization degree was indicative of lower risk for LMM (OR = 0.88, 95%CI 0.79-0.98). GEE further revealed that overall support degree was negatively associated with risk for sarcopenia (OR = 0.86, 95%CI 0.76-0.98) and LMM (OR = 0.87, 95%CI 0.77-0.99). Objective support was neither significantly associated with sarcopenia nor its traits. No significant interaction effect was observed between overall support and the concerned confounders on sarcopenia (interaction P-value > 0.05). CONCLUSION: Overall social support degree was negatively associated with sarcopenia risk, possibly primarily through affecting muscle mass rather than muscle strength or physical performance, and such an association remained robust across subgroups with distinct characteristics. This holds implications for policymakers to conduct population-based risk assessment, and supportive strategies against sarcopenia should focus on enhancing subjective support and support utilization rather than objective support alone.

Development and Validation of PRE-SARC (PREdiction of SARCopenia Risk in Community Older Adults) Sarcopenia Prediction Model.

OBJECTIVE: Reliable identification of high-risk older adults who are likely to develop sarcopenia is essential to implement targeted preventive measures and follow-up. However, no sarcopenia prediction model is currently available for community use. Our objective was to develop and validate a risk prediction model for calculating the 1-year absolute risk of developing sarcopenia in an aging population. METHODS: One prospective population-based cohort of non-sarcopenic individuals aged 60 years or older were used for the development of a sarcopenia risk prediction model and model validation. Sarcopenia was defined according to the 2019 Asian Working Group for Sarcopenia consensus. Stepwise logistic regression was used to identify risk factors for sarcopenia incidence within a 1-year follow-up. Model performance was evaluated using the area under the receiver operating characteristics curve (AUROC) and calibration plot, respectively. RESULTS: The development cohort included 1042 older adults, among whom 87 participants developed sarcopenia during a 1-year follow-up. The PRE-SARC (PREdiction of SARCopenia Risk in community older adults) model can accurately predict the 1-year risk of sarcopenia by using 7 easily accessible community-based predictors. The PRE-SARC model performed well in predicting sarcopenia, with an AUROC of 87% (95% CI, 0.83-0.90) and good calibration. Internal validation showed minimal optimism, with an adjusted AUROC of 0.85. The prediction score was categorized into 4 risk groups: low (0%-10%), moderate (>10%-20%), high (>20%-40%), and very high (>40%). The PRE-SARC model has been incorporated into an online risk calculator, which is freely accessible for daily clinical applications (https://sarcopeniariskprediction.shinyapps.io/dynnomapp/). CONCLUSIONS: In community-dwelling individuals, the PRE-SARC model can accurately predict 1-year sarcopenia incidence. This model serves as a readily available and free accessible tool to identify older adults at high risk of sarcopenia, thereby facilitating personalized early preventive approaches and optimizing the utilization of health care resources.

Investigating association between gut microbiota and sarcopenia-related traits: a Mendelian randomization study.

Background: Observational studies have indicated a potential link between gut microbiota and sarcopenia. However, the underlying mechanisms and a causal relationship have not been established. Thus, the objective of this study is to examine the possible causal association between gut microbiota and sarcopenia-related traits, including low hand-grip strength and appendicular lean mass (ALM), to shed light on the gut-muscle axis. Methods: To investigate the potential impact of gut microbiota on low hand-grip strength and ALM, we utilized a two-sample Mendelian randomization (MR) approach. Summary statistics were obtained from genome-wide association studies of gut microbiota, low hand-grip strength, and ALM. The primary MR analysis employed the random-effects inverse-variance weighted (IVW) method. To assess the robustness, we conducted sensitivity analyses using the MR pleiotropy residual sum and outlier (MR-PRESSO) test to detect and correct for horizontal pleiotropy, as well as the MR-Egger intercept test and leave-one-out analysis. Results: Alcaligenaceae, Family XIII, and Paraprevotella were positively associated with the risk of low hand-grip strength (P-values < 0.05). Streptococcaceae were negatively associated with low hand-grip strength (P-values < 0.05). Eight bacterial taxa (Actinomycetales, Actinomycetaceae, Bacteroidaceae, Porphyromonadaceae, Prevotellaceae, Bacteroides, Marvinbryantia, and Phascolarctobacterium) were associated with a higher risk of ALM (P-values < 0.05). Eubacterium fissicatena group was negatively associated with ALM (P-values < 0.05). Conclusion: We found several gut microbiota components causally associated with sarcopenia-related traits. Our findings provided insights into novel strategies for the prevention and treatment of sarcopenia through the regulation of the gut microbiota, contributing to a better understanding of the gut-muscle axis.

Biomass fuel usage for cooking and frailty among older adults in China: a population-based cohort study.

Background: Although outdoor air pollution is reported to have a negative effect on frailty, evidence involving household air pollution is sparse. Methods: A cohort study on older participants aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey was conducted between 2011/2012 and 2014. Household cooking fuel types were determined by self-reported questionaries, and were dichotomized into clean or biomass fuels. The frailty status was evaluated via a 46-item frailty index (FI) and the FRAIL scale, respectively. Frailty was identified if FI >0.21 or FRAIL score ≥3. Cox proportional hazards models were employed to examine the relationship between cooking fuels and incident frailty. And the effects of swapping cooking fuels on frailty risk were also explored. Results: Among 4,643 participants (mean age at baseline 80.9 ± 9.6 years, 53.7% male) totaling 11,340 person-years, 923 (19.9%) incident frailty was identified using FI. Compared to clean fuels, cooking with biomass fuels was intricately linked to a 23% rise in frailty risk (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.06-1.43). A similar association was detected between biomass cooking fuels and frailty measured by the FRAIL scale (HR 1.24, 95% CI 1.04-1.50). Sensitive analyses supported the independent relationship between biomass fuels and frailty. Stratified analyses revealed that the frailty risk was higher among town residents (HR 1.44, 95% CI 1.13-1.84) and participants not exercising regularly (HR 1.35, 95% CI 1.11-1.64). In comparison with persistent biomass fuels usage, switching to clean fuels had a trend to reduce the frailty risk, and the opposite effect was observed when swapping from clean to biomass fuels. Conclusion: Cooking with biomass fuels was associated with an increased frailty risk in older adults, especially amongst those living in town and those lacking regular exercise. More studies are needed to confirm our findings and to evaluate the potential benefits of reducing indoor biomass fuel usage.

Tooth loss, denture use, and all-cause and cause-specific mortality in older adults: a community cohort study.

Objectives: The available evidence on the connections between tooth loss, denture use, and mortality from all causes or specific causes among older adults is inconclusive. Therefore, we aimed to investigate the association between tooth loss, denture use, and all-cause and cause-specific mortality in older adults. Methods: A cohort of 5,403 participants aged 65 and older were recruited in the 2014 Chinese Longitudinal Healthy Longevity Survey wave and followed up in the 2018 wave. Cox proportional hazard models were used to examine the association between the number of natural teeth, denture use, and all-cause and cause-specific mortality. Results: During a mean (SD) follow-up of 3.1 years (1.3), 2,126 deaths (39.3%) occurred. Individuals with 0 and 1-9 teeth had higher mortality due to all-cause, cardiovascular disease (CVD), cancer, and other causes (all p-trend <0.05) than those with 20+ teeth. At the same time, no association was found with respiratory disease mortality. Participants who used dentures had lower mortality due to all causes [hazard ratios (HR) 0.79, 95% confidence intervals (CI) 0.71-0.88], CVD (HR 0.80, 95% CI 0.64-1.00), respiratory disease (HR 0.66, 95% CI 0.48-0.92), and other causes (HR 0.77, 95% CI 0.68-0.88) than those without dentures. Joint analysis revealed that older adults with fewer natural teeth and no dentures had higher mortality. Additionally, interaction analyses showed that the effects of the number of natural teeth on all-cause mortality were more pronounced in older adults aged <80 years (p-value for interaction = 0.03). Conclusion: Having fewer natural teeth, particularly less than 10 teeth, is linked to an increased risk of mortality from all causes, including CVD, cancer, and other causes, but not respiratory disease. The use of dentures would mitigate the adverse impact of tooth loss on all-cause and some cause-specific mortality.