Usual Pace Research Articles

The causal relationships between iron status and sarcopenia in Europeans: a bidirectional two-sample Mendelian randomization study.

Previous studies have indicated potential associations between metals, lifestyle factors, and sarcopenia. However, the specific causal relationships between iron status, lifestyle factors, and sarcopenia remain unclear. Therefore, we conducted a bidirectional two-sample Mendelian Randomization (MR) approach to investigate these relationships. The exposure variables included iron status, living alone, coffee intake, alcohol taken with meals, and moderate physical activity, while the outcome variable was sarcopenia, assessed by grip strength in both hands and usual walking pace. We employed the Weighted Median (WM), the Inverse Variance-Weighted (IVW), and other MR methods to explore these problems for analysis. Simultaneously, we conducted a bidirectional MR analysis to assess whether sarcopenia has a reverse causal relationship with internal iron status. In our present research, we found serum iron (P = 0.033), ferritin (P = 0.001), transferrin saturation (P = 0.029) and coffee intake (P = 0.002) revealed a negative trend for sarcopenia, living alone (P = 0.022) and alcohol taken with meal (P = 0.006) showed a opposite trend for sarcopenia. Whereas sarcopenia showed negative trend for ferritin (P = 0.041) and transferrin saturation (P = 0.043), showed the opposite trend for transferrin (P = 0.021). Our study suggested that higher serum iron levels might reduce the risk of sarcopenia. Moreover, living alone and alcohol consumption might increase the sarcopenia risk, while coffee intake and moderate physical activity could reduce the sarcopenia risk.

Causal relationship between sarcopenia and rotator cuff tears: a Mendelian randomization study.

Sarcopenia and rotator cuff tears are common among elderly patients. However, the role of sarcopenia in the management of rotator cuff tears has been often overlooked. This study aimed to elucidate the effects of sarcopenia-related traits on rotator cuff tears. Two-sample Mendelian randomization (MR) analyses based on genome-wide association study data were used to evaluate the causal relationships among appendicular lean mass (ALM), usual walking pace, low hand grip strength, and rotator cuff tears. Multivariate Mendelian randomization (MVMR) analyses were used to evaluate the direct effects of each muscle trait on the causal relationship. Univariate MR analysis showed that ALM and usual walking pace were causally related to rotator cuff tears (odds ratio (OR) = 0.895; 95% confidence interval (CI), 0.758-0.966, P<0.001 and OR = 0.458, 95% CI, 0.276-0.762, P = 0.003, respectively), and there was no evidence of causality between low hand grip strength and rotator cuff tears (OR = 1.132, 95% CI, 0.913-1.404, P = 0.26). MVMR analysis confirmed the causal effects of ALM and walking pace on rotator cuff tears (OR = 0.918, 95% CI, 0.851-0.990, P = 0.03 and OR = 0.476, 95% CI, 0.304-0.746, P = 0.001, respectively). A causal genetic relationship exists between sarcopenia and rotator cuff tears. Sarcopenia-related traits including low muscle mass and physical function, increase the risk of rotator cuff tears. These findings provide new clinical insights and evidence-based medicine to optimize management of rotator cuff tears.

Educational attainment, brain cortical structure, and sarcopenia: a Mendelian randomization study.

Previous observational studies have suggested associations between high-level educational attainment (EA) and a lower risk of sarcopenia. However, the causality inferred from those studies was subjected to residual confounding and reverse causation. The protective effect of EA on sarcopenia may be mediated via changes in brain cortical structure. The aim of this study was to use a two-step Mendelian randomization (MR) analysis to illustrate the causal relationship between EA, brain cortical structure, and sarcopenia. Instrumental variables at the genome-wide significance level were obtained from publicly available datasets, and inverse variance weighted as the primary method was used for MR analysis. We perform several sensitivity analyses, including Cochran Q test, MR-Egger intercept test, leave-one-out analyses, and MR Pleiotropy Residual Sum and Outlier to evaluate the reliability of the results. EA was causally associated with increased appendicular lean mass (β = 0.25, 95% confidence interval (CI): 0.19 to 0.31, p = 2.25 × 10-15), hand grip strength (left: β = 0.042, 95% CI: 0.013 to 0.071, p = 4.77 × 10-3 and right: β = 0.050, 95% CI: 0.022 to 0.079, p = 5.17 × 10-4), and usual walking pace (β = 0.20, 95% CI: 0.18 to 0.22, p = 6.16 × 10-83). In addition, EA was associated with increased brain cortical surface area (β = 4082.36, 95% CI: 2513.35 to 5681.38, p = 3.40 × 10-7) and cortical thickness (TH) (β = 0.014, 95% CI: 0.0045 to 0.023, p = 3.45 × 10-3). Regarding the causal effect of EA on usual walking pace, the mediatory effect of TH was 0.0069 and the proportion of mediation by TH was 3.43%. The study will have revealed the protective causal effect of EA on sarcopenia, which provides a reference for the prevention of sarcopenia at the public health level. We also will have found EA could affect the brain cortical structure, and the brain cortical structure could mediate the protective effect of EA against sarcopenia risk.

Exploring the relationship between sarcopenia and 11 respiratory diseases: a comprehensive mendelian randomization analysis

BackgroundSarcopenia (SP) is an aging-related loss of muscle mass and function, affecting the respiratory system. However, the causality of the association between sarcopenia on lung diseases remains elusive.MethodsThe bidirectional univariate Mendelian randomization (UVMR), multivariate MR (MVMR) analysis, and mediation MR were utilized to systematically investigate the genetic causal relationship of SP and 11 respiratory diseases. Independent genomic variants related to sarcopenia or respiratory diseases were identified as instrumental variables (IVs), and the summary level data of genome-wide associated studies (GWAS) were obtained from the UK biobank and FinnGen. MVMR analysis was conducted to explore the mediation effects of body mass index (BMI), Alcohol Use Disorders Identification Test (AUDIT), smoking, education attainment (EA), physical activity, and Type 2 Diabetes Mellitus (T2DM).ResultsForward UVMR analysis based on the primary method revealed that pneumoconiosis was associated with a higher risk of appendicular lean mass (ALM) (OR = 1.01, p = 0.03), and BMI (10.65%), smoking (10.65%), and physical activity (17.70%) had a mediating role in the effect of pneumoconiosis on ALM. In reverse MR analysis, we found that genetically predicted ALM was significantly associated with an increased risk of pulmonary embolism (PE) (OR = 1.24, p = 7.21E-05). Chronic obstructive pulmonary disease (COPD) (OR = 0.98, p = 0.002) and sarcoidosis (OR = 1.01, p = 0.004) were identified to increase the loss of left-hand grip strength (HGS). Conversely, the increase in left- HGS presented a protective effect on chronic bronchitis (CB) (OR = 0.35, p = 0.03), (OR = 0.80, p = 0.02), and asthma (OR = 0.78, p = 0.04). Similarly, the loss of the right-HGS elevated the risk of low respiratory tract infection (LRTI) (OR = 0.97, p = 0.02) and bronchiectasis (OR = 1.01, p = 0.03), which is also an independent protective factor for LRTI and asthma. In the aspects of low HGS, the risk of LRTI was increased after MVMR analysis, and the risk of sarcoidosis and pneumoconiosis was elevated in the reverse analysis. Lastly, asthma was found to be related to the loss of the usual walking pace, and the reverse MR analysis suggested a causal relationship between the usual walking pace and LRTI (OR = 0.32, p = 2.79 × 10−5), asthma (OR = 0.24, p = 2.09 × 10−6), COPD (OR = 0.22, p = 6.64 × 10−4), and PE(OR = 0.35, p = 0.03).ConclusionsThis data-driven MR analysis revealed SP was bidirectional causally associated with lung diseases, providing genetic evidence for further mechanistic and clinical studies to understand the crosstalk between SP and lung diseases.

Ischemic stroke and sarcopenia have an asymmetric bidirectional relationship based on a two-sample Mendelian randomization study.

We investigated the potential relationship between age-related conditions, particularly sarcopenia and ischemic stroke (IS), through a two-sample Mendelian randomization (MR) study. We conducted a two-sample bidirectional MR study to investigate the relationship between sarcopenia and stroke. Genetic instruments for sarcopenia were derived from the UK Biobank, while data on IS and its subtypes were obtained from the MEGASTROKE consortium. Inverse variance weighting (IVW) served as the primary analytical method. Additionally, heterogeneity and pleiotropy were assessed to ensure the robustness of the findings. The analysis indicates a negative correlation between appendicular lean mass (ALM) and small vessel stroke (SVS; OR = 0.790, 95% CI: 0.703-0.888, p < 0.001), a positive correlation with cardioembolic stroke (CES; OR = 1.165, 95% CI: 1.058-1.284, p = 0.002), and no causal relationship with any ischemic stroke (AIS) or large artery stroke (LAS). Additionally, SVS is negatively associated with right-hand grip strength (OR = 0.639, 95% CI: 0.437-0.934, p = 0.021), while AIS, LAS, and CES do not exhibit a causal relationship with grip strength. Furthermore, no causal relationship was identified between left-hand grip strength, usual walking pace, and IS or its subtypes. MR analysis reveals only a negative association between CES and usual walking pace (OR = 0.989, 95% CI: 0.980-0.998, p = 0.013), with no associations found between other IS subtypes and sarcopenia-related traits. This study demonstrates that a reduction in ALM and right-hand grip strength is associated with SVS, whereas decreased ALM may serve as a protective factor against CES. Conversely, our analysis suggests that CES can impact walking speed. Overall, these findings provide valuable insights into the prevention and treatment of these conditions.

Spatiotemporal Gait Characteristics and Neuropsychological Performance in Midlife

Abstract Background Midlife risk factors such as Type 2 Diabetes Mellitus (T2DM) confer a significantly increased risk of cognitive impairment in later life, with executive function, memory and attention domains often affected first. Spatiotemporal gait characteristics are increasingly recognised as biomarkers of neurocognitive function and later dementia risk. Methods Using an automated walkway, 24 spatiotemporal gait parameters were examined across 5 domains of gait previously linked to cognitive function on usual-pace, maximal-pace, and cognitive dual-task gait conditions. Neurocognitive function was measured using a neuropsychological assessment battery. Linear regression was used assess the relationship between each gait parameter across the three walks and cognitive function. Results 102 middle-aged adults underwent assessment, 65 with uncomplicated T2DM (57.5 ± 8.0 years; 40% female) and 37 healthy controls (57.0 ± 8.3 years; 62.1% female). T2DM was associated with significant changes in gait phases and rhythm domains at usual-pace, and greater gait variability observed during maximal-pace and dual-task. In the overall cohort, both gait pace and rhythm domains were associated with memory and executive function during usual pace walking. At maximal-pace, gait pace parameters were associated with reaction time and delayed memory. During the cognitive dual-task, associations between gait variability and delayed memory and executive function were observed. Associations persisted following covariate adjustment and did not differ by T2DM status. Conclusion This supports the use of spatiotemporal gait as an integrative biomarker of neurocognitive function in otherwise healthy middle-aged individuals. Discrete associations were seen between both differing gait tasks and gait domains with domain-specific neuropsychological performance. Employing both maximal-pace and dual-task paradigms, in addition to single-task usual-pace gait, may be important in cognitively unimpaired populations with risk factors for later cognitive decline - with the aim of identifying individuals who may benefit most from potential preventative interventions.

Causal relationship between non-alcoholic fatty liver disease and sarcopenia: a bidirectional Mendelian randomization study.

A correlation between non-alcoholic fatty liver disease and sarcopenia is demonstrated, but the causality remains unclear. Our study aims to clarify the point of genetics between non-alcoholic fatty liver disease (NAFLD) and sarcopenia at the level of gene prediction through two-sample Mendelian randomization (MR) analysis. The study employed the two-sample MR approach to investigate the bi-directional causality between NAFLD and sarcopenia. Published summary statistics were used to obtain instrumental variables (IVs) at the genome-wide significance level. IVW analysis showed that the risk of NAFLD was reduced when walking pace was increased (OR = 0.435, 95%CI 0.240-0.789, p = 0.006); Increasing appendicular lean mass (ALM) decreased the risk of NAFLD (OR = 0.906, 95%CI 0.838-0.980, p = 0.014); Those older than 60 were more likely to suffer from NAFLD if they had low grip strength (OR = 1.411, 95%CI 1.087-1.830, p = 0.0012). In the reverse MR study, weight median analysis showed that NAFLD caused a decrease in ALM (OR = 0.953, 95%CI 0.957-0.994, p = 0.001); whereas NAFLD showed no correlation with usual walking pace or grip strength (all with p > 0.05). MR-Egger regression analysis showed that there was no horizontal pleiotropy in the SNPs (all with p > 0.05). The characteristics related to sarcopenia (usual walking pace, appendicular lean mass and low hand grip strength) may play a causal role in the development of nonalcoholic fatty liver disease, although the underlying mechanisms need to be further investigated. The presence of specific single nucleotide polymorphisms (SNPs) such as rs3747207, rs429358, and rs73001065 has been identified in the PNPLA3, APOE, and MAU2 proteins. These genetic markers represent potential targets for future interventions aimed at addressing, managing, or mitigating the risk of NAFLD.

The relationship between serum lipid with sarcopenia: Results from the NHANES 2011–2018 and bidirectional Mendelian randomization study

BackgroundThe relationship between serum lipids and sarcopenia remains unclear due to conflicting results in previous studies. ObjectiveTo explore the associations and potential causality between serum lipids, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC), and sarcopenia. MethodsData from the National Health and Nutrition Examination Survey (NHANES) were analysed using multivariable regression and restricted cubic splines (RCSs) to assess the associations between serum lipids and sarcopenia. Bidirectional Mendelian randomization (MR) was employed to investigate the causal relationships with sarcopenia-related traits such as appendicular lean mass (ALM), hand grip strength, and usual walking pace. ResultsSerum HDL-C and TG levels were inversely associated with ALMBMI, with each 1-unit increase linked to a 0.13 % and 1.32 % decrease, respectively. Elevated TG, but not HDL-C, LDL-C, or TC levels, was significantly associated with an increased risk of sarcopenia (P for trend = 0.001). RCS analysis revealed a log-shaped dose-response relationship between TG and sarcopenia risk (P overall <0.001, P non-linear <0.001), with a cutoff value of 92.75 mg/dL. Genetically predicted HDL-C, LDL-C, and TG were associated with ALM. Conversely, ALM showed an inverse causal relationship with all four serum lipids. Additionally, genetically predicted usual walking pace influenced HDL-C and TG levels (P < 0.001). ConclusionThe study reveals a nonlinear association between TG levels and sarcopenia risk, and a bidirectional association between lipid profiles and muscle mass, underscoring the need for further research to elucidate these mechanisms.

Causal effect of lifestyle and metabolic indicator with herpes zoster: a two-sample Mendelian randomization study.

Previous observational studies have reported certain causal relationships between factors such as smoking, alcohol consumption, obesity, physical activity, metabolic disorders, and the incidence of herpes zoster (HZ). However, there is controversy regarding the observed results across different studies. Our objective was to investigate the causal effects of these risk factors on the risk of herpes zoster through a Mendelian randomization analysis using two-sample bidirectional approaches. We conducted two-sample bidirectional Mendelian randomization analyses to explore the causal relationships between different lifestyles, obesity assessment indices, metabolic indicators, and the risk of herpes zoster. All exposure and outcome data were sourced from publicly available data from genome-wide association studies. In the inverse-variance weighted (IVW) analysis, body mass index (BMI) (OR: 1.160, 95% CI: 1.030-1.307, p = 0.014), Body fat percentage (BFP) (OR: 1.241, 95% CI: 1.050-1.467, p = 0.011), and whole body fat mass (WBFM) (OR: 1.199, 95% CI: 1.057-1.362, p = 0.005) exhibited positive associations with the risk of HZ. However, usual walking pace (UWP) (OR: 0.498, 95% CI: 0.254-0.976, p = 0.042) demonstrated a significant negative correlation with HZ risk. Other factors including alcohol intake frequency, smoking initiation, smoking status, insomnia, and sleep duration did not show significant causal relationships with HZ. Mendelian randomization studies revealed that BMI, BFP, and WBFM are risk factors for HZ. UWP showed a protective effect against HZ. These findings provide a straightforward method for evaluating future clinical practices aiming to develop personalized management strategies and assess high-risk populations for HZ.

Physical Function and Mortality in Older Adults with Chronic Kidney Disease.

Accurate mortality prediction can guide clinical care for older adults with chronic kidney disease (CKD). Yet existing tools do not incorporate physical function, an independent predictor of death in older adults. We determined whether incorporating physical function measurements improve mortality prediction among older adults with CKD. We included Chronic Renal Insufficiency Cohort participants who were ≥65 years old, had estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73m2, not receiving kidney failure replacement therapy (KFRT), and had least one gait speed assessment. Gait speed was measured at usual pace (≥0.84, 0.83-0.65, 0.64-0.47, ≤0.46 meters/second, or unable), and frailty was assessed using Physical Frailty Phenotype criteria (range 0 to 5 points, also known as Fried criteria). We modeled time to all-cause death over five years using Cox proportional hazard models, treating KFRT as censored and non-censored events in separate analyses. C-statistics assessed model discrimination. Among 2,338 persons, mean age was 70±4 years; 43% were female and 43% were Black. Mean eGFR was 42±13 mL/min/1.73m2 and median urine albumin-to-creatinine ratio was 33 mg/g [Q1 9, Q3 206]. Over a median follow-period of 5 years, 392 died and 164 developed KFRT. In censored analyses, adding gait speed or frailty improved mortality risk prediction. The C-statistic changed from 0.69 to 0.72 with gait speed scores, and from 0.70 to 0.73 with frailty scores. The performance of models with gait speed or frailty was similar in non-censored analyses. Among older adults with CKD, adding measures of physical function modestly improves mortality prediction.

2200 Association between gait speed deterioration and EEG abnormalities

Abstract Introduction Physical and cognitive decline at an older age is preceded by changes that accumulate over time until they become clinically evident difficulties. These changes, frequently overlooked by patients and health professionals, may respond better than fully established conditions to strategies designed to prevent disabilities and dependence in later life. The objective of this study was twofold: to provide further support for the need to screen for early functional changes in older adults and to look for an early association between decline in mobility and cognition. Methods A cross-sectional cohort study was conducted on 95 active functionally independent community-dwelling older adults in Havana, Cuba. We measured their gait speed at the usual pace and their cognitive status using the MMSE. A value of 0.8 m/s was used as the cut-off point to decide whether they presented a decline in gait speed. A quantitative analysis of their EEG at rest was also performed to look for an associated subclinical decline in brain function. Results Results show that 70% of the sample had a gait speed deterioration (i.e. lower than 0.8 m/s), of which 80% also had an abnormal EEG frequency composition for their age. While there was no statistically significant difference in the MMSE score between participants with a gait speed above and below the selected cut-off, individuals with MMSE scores below 25 also had a gait speed&amp;lt;0.8 m/s and an abnormal EEG frequency composition. Conclusions Our results provide further evidence of early decline in older adults – even if still independent and active - and point to the need for clinical pathways that incorporate screening and early intervention targeted at early deterioration to prolong the years of functional life in older age.

Reliability and concurrent validity of the Active Movement Scale (AMS) in adults with musculoskeletal disorders.

The Active Movement Scale (AMS) is a brief screen for identifying movement impairments affecting functional task performance. To assess inter-rater reliability, test-retest reliability, floor and ceiling effects, and concurrent validity of the AMS in adults with musculoskeletal disorders. Fifty-five subjects (mean age: 61.3±15.3 years) transitioning from physical therapy attended two sessions. The 14-item AMS was assessed by two therapists, resulting in a total score (AMST) and two sub-scores: upper body (AMSU) and lower body (AMSL). Moreover, subjects completed PROMIS Physical Function-10a (PPF), Lifestyle Physical Function (LPF), Cardio Activity Level (CAL) surveys, Two Square Agility Test (TSAT), WorkAbility Rate of Manipulation Turning (WRMT) and Placing (WRMP), Grip Strength (GS), 10-Meter Walk Usual (GSU) and Fast (GSF) pace, and Grooved Pegboard Placing (GPP) and Remove (GPR) tests. Inter-rater reliability coefficients for AMST, AMSU, and AMSL were 0.96, 0.92, and 0.96, respectively, with individual item reliability ranging from 0.58 to 1.0. Test-retest reliability for these assessments yielded coefficients of 0.93, 0.84, and 0.94, with individual item reliability ranging from 0.47 to 0.88. No floor effects were observed, but mild ceiling effects were noted. AMST showed a high correlation with LPF (r = 0.72) and moderate correlation with PPF (r = 0.64) surveys. AMSU had moderate correlations with GPP (r = 0.61) and WRMP (r = 0.57) tests, while AMSL correlated moderately with GSF (r = 0.55) and TSAT (r = 0.50) tests. This study provides evidence of the reliability and validity of AMS in adults with musculoskeletal disorders to support transitions between rehabilitation and fitness programs.

Effects of walking on epigenetic age acceleration: a Mendelian randomization study

IntroductionWalking stands as the most prevalent physical activity in the daily lives of individuals and is closely associated with physical functioning and the aging process. Nonetheless, the precise cause-and-effect connection between walking and aging remains unexplored. The epigenetic clock emerges as the most promising biological indicator of aging, capable of mirroring the biological age of the human body and facilitating an investigation into the association between walking and aging. Our primary objective is to investigate the causal impact of walking with epigenetic age acceleration (EAA).MethodsWe conducted a two-sample two-way Mendelian randomization (MR) study to investigate the causal relationship between walking and EAA. Walking and Leisure sedentary behavior data were sourced from UK Biobank, while EAA data were gathered from a total of 28 cohorts. The MR analysis was carried out using several methods, including the inverse variance weighted (IVW), weighted median, MR-Egger, and robust adjusted profile score (RAPS). To ensure the robustness of our findings, we conducted sensitivity analyses, which involved the MR-Egger intercept test, Cochran’s Q test, and MR-PRESSO, to account for and mitigate potential pleiotropy.ResultsThe IVW MR results indicate a significant impact of usual walking pace on GrimAge (BETA = − 1.84, 95% CI (− 2.94, − 0.75)), PhenoAge (BETA = − 1.57, 95% CI (− 3.05, − 0.08)), Horvath (BETA = − 1.09 (− 2.14, − 0.04)), and Hannum (BETA = − 1.63, 95% CI (− 2.70, − 0.56)). Usual walking pace is significantly associated with a delay in epigenetic aging acceleration (EAA) (P < 0.05). Moreover, the direction of effect predicted by the gene remained consistent across RAPS outcomes and sensitivity MR analyses. There is a lack of robust causal relationships between other walking conditions, such as walking duration and walking frequency, on EAA (P > 0.05).ConclusionOur evidence demonstrates that a higher usual walking pace is associated with a deceleration of the acceleration of all four classical epigenetic clocks acceleration.

Association of lipid-lowering drugs with risk of sarcopenia: a drug target mendelian randomization study and meta-analysis

BackgroundLipid-lowering drugs are widely used among the elderly, with some studies suggesting links to muscle-related symptoms. However, the causality remains uncertain.MethodsUsing the Mendelian randomization (MR) approach, we assessed the causal effects of genetically proxied reduced low-density lipoprotein cholesterol (LDL-C) through inhibitions of hydroxy-methyl-glutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and Niemann-Pick C1-like 1 (NPC1L1) on sarcopenia-related traits, including low hand grip strength, appendicular lean mass, and usual walking pace. A meta-analysis was conducted to combine the causal estimates from different consortiums.ResultsUsing LDL-C pooled data predominantly from UK Biobank, genetically proxied inhibition of HMGCR was associated with higher appendicular lean mass (beta = 0.087, P = 7.56 × 10− 5) and slower walking pace (OR = 0.918, P = 6.06 × 10− 9). In contrast, inhibition of PCSK9 may reduce appendicular lean mass (beta = -0.050, P = 1.40 × 10− 3), while inhibition of NPC1L1 showed no causal impact on sarcopenia-related traits. These results were validated using LDL-C data from Global Lipids Genetics Consortium, indicating that HMGCR inhibition may increase appendicular lean mass (beta = 0.066, P = 2.17 × 10− 3) and decelerate walking pace (OR = 0.932, P = 1.43 × 10− 6), whereas PCSK9 inhibition could decrease appendicular lean mass (beta = -0.048, P = 1.69 × 10− 6). Meta-analysis further supported the robustness of these causal associations.ConclusionsGenetically proxied HMGCR inhibition may increase muscle mass but compromise muscle function, PCSK9 inhibition could result in reduced muscle mass, while NPC1L1 inhibition is not associated with sarcopenia-related traits and this class of drugs may serve as viable alternatives to sarcopenia individuals or those at an elevated risk.

Discrete Relationships between Spatiotemporal Gait Characteristics and Domain-Specific Neuropsychological Performance in Midlife.

Midlife risk factors such as type 2 diabetes mellitus (T2DM) confer a significantly increased risk of cognitive impairment in later life with executive function, memory, and attention domains often affected first. Spatiotemporal gait characteristics are emerging as important integrative biomarkers of neurocognitive function and of later dementia risk. We examined 24 spatiotemporal gait parameters across five domains of gait previously linked to cognitive function on usual-pace, maximal-pace, and cognitive dual-task gait conditions in 102 middle-aged adults with (57.5 ± 8.0 years; 40% female) and without (57.0 ± 8.3 years; 62.1% female) T2DM. Neurocognitive function was measured using a neuropsychological assessment battery. T2DM was associated with significant changes in gait phases and rhythm domains at usual pace, and greater gait variability observed during maximal pace and dual tasks. In the overall cohort, both the gait pace and rhythm domains were associated with memory and executive function during usual pace. At maximal pace, gait pace parameters were associated with reaction time and delayed memory. During the cognitive dual task, associations between gait variability and both delayed memory/executive function were observed. Associations persisted following covariate adjustment and did not differ by T2DM status. Principal components analysis identified a consistent association of slower gait pace (step/stride length) and increased gait variability during maximal-pace walking with poorer memory and executive function performance. These data support the use of spatiotemporal gait as an integrative biomarker of neurocognitive function in otherwise healthy middle-aged individuals and reveal discrete associations between both differing gait tasks and gait domains with domain-specific neuropsychological performance. Employing both maximal-pace and dual-task paradigms may be important in cognitively unimpaired populations with risk factors for later cognitive decline-with the aim of identifying individuals who may benefit from potential preventative interventions.

Agreement and Associations between Countermovement Jump, 5-Time Sit-To-Stand, Lower-Limb Muscle Power Equations, and Physical Performance Tests in Community-Dwelling Older Adults.

Objectives: The present study examined the agreement and associations of the 5-time sit-to-stand (5STS) test, the countermovement jump test, and lower-limb muscle power equations with a set of physical performance tests in older adults. Methods: Five hundred and thirty-four community-dwelling older adults were recruited for the study. Lower-limb muscle power measures included 5STS, the countermovement jump test, and muscle power equations. Isometric handgrip strength, timed "up-and-go!", the 6 min walking test, one-leg stand, and walking speed at usual and fast paces were used to assess physical performance. Pearson's correlations and Bland-Altman analyses were conducted to examine associations among muscle power measures. Linear and multiple regressions were run to explore associations of 5STS, the countermovement jump test, and muscle power equations with physical performance tests. Results: Weak correlations were observed among lower-limb muscle power measures. Bland-Altman results indicated important differences among the countermovement jump test, 5STS, and muscle power equations. Results of multiple linear regressions indicated that 5STS, the countermovement jump test, and muscle power equations were significantly associated with measures of muscle strength and mobility. However, only 5STS was significantly associated with balance. Conclusions: Our results indicate that the performance on the countermovement jump test and 5STS is weakly correlated with lower-limb muscle power equations. The only exception was the correlation found between the countermovement jump test and relative muscle power, highlighting the importance of accounting for body mass in muscle power evaluations. Muscle power measures were similarly associated with performance on handgrip strength, timed "up-and-go!", and the 6 min walking test. The exclusive association of 5STS with balance suggests that a reassessment of 5STS muscle power equations may be warranted.

Association between gait speed deterioration and EEG abnormalities.

Physical and cognitive decline at an older age is preceded by changes that accumulate over time until they become clinically evident difficulties. These changes, frequently overlooked by patients and health professionals, may respond better than fully established conditions to strategies designed to prevent disabilities and dependence in later life. The objective of this study was twofold; to provide further support for the need to screen for early functional changes in older adults and to look for an early association between decline in mobility and cognition. A cross-sectional cohort study was conducted on 95 active functionally independent community-dwelling older adults in Havana, Cuba. We measured their gait speed at the usual pace and the cognitive status using the MMSE. A value of 0.8 m/s was used as the cut-off point to decide whether they presented a decline in gait speed. A quantitative analysis of their EEG at rest was also performed to look for an associated subclinical decline in brain function. Results show that 70% of the sample had a gait speed deterioration (i.e., lower than 0.8 m/s), of which 80% also had an abnormal EEG frequency composition for their age. While there was no statistically significant difference in the MMSE score between participants with a gait speed above and below the selected cut-off, individuals with MMSE scores below 25 also had a gait speed<0.8 m/s and an abnormal EEG frequency composition. Our results provide further evidence of early decline in older adults-even if still independent and active-and point to the need for clinical pathways that incorporate screening and early intervention targeted at early deterioration to prolong the years of functional life in older age.

Acceptability, Reliability, and Validity of Virtually Administered Gait Speed Tests

ObjectivesTo evaluate the acceptability, reliability (inter- and intrarater), and validity (convergent, known groups, and predictive) of virtually administered gait speed tests for community-dwelling older adults. DesignA prospective cohort study was performed, tracking health outcomes for a year. Setting and ParticipantsThe 3-m gait speed test at usual and fast pace was administered to community-dwelling older adults over Zoom. MethodTo examine acceptability, participants completed questionnaires regarding telehealth usability and experience. Virtual gait speed tests were administered at baseline and 24 to 72 hours later to evaluate reliability. Self-report mobility measures were used to examine convergent and known-groups validity. Participants’ health outcomes were tracked for a year to evaluate predictive validity. ResultsSixty participants completed the baseline assessment and 52 completed the second assessment. Participants reported an overall positive experience with the test. Intraclass correlation coefficients for reliability ranged from 0.79 to 0.90. For convergent validity, correlations >0.30 were found predominantly for usual gait speed with self-report mobility measures. Both the usual- and fast-gait speed were able to discriminate between difficulty walking and gait aid use. Usual gait speed was able to predict specialist and family doctor visits and fast gait speed was able to predict rehabilitation specialist visits over 1 year. Conclusions and ImplicationsOur findings demonstrate support for the acceptability, reliability, and validity of virtually administered gait speed tests for community-dwelling older adults. Although future studies are needed to examine the validity of virtual gait speed tests in larger and more diverse samples to improve generalizability of results, clinicians and researchers can virtually administer 3-m gait speed tests with confidence that scores are trustworthy and reflect older adults’ mobility.

Genetic and phenotypic associations of frailty with cardiovascular indicators and behavioral characteristics

IntroductionFrailty Index (FI) is a common measure of frailty, which has been advocated as a routine clinical test by many guidelines. The genetic and phenotypic relationships of FI with cardiovascular indicators (CIs) and behavioral characteristics (BCs) are unclear, which has hampered ability to monitor FI using easily collected data. ObjectivesThis study is designed to investigate the genetic and phenotypic associations of frailty with CIs and BCs, and further to construct a model to predict FI. MethodGenetic relationships of FI with 288 CIs and 90 BCs were assessed by the cross-trait LD score regression (LDSC) and Mendelian randomization (MR). The phenotypic data of these CIs and BCs were integrated with a machine-learning model to predict FI of individuals in UK-biobank. The relationships of the predicted FI with risks of type 2 diabetes (T2D) and neurodegenerative diseases were tested by the Kaplan-Meier estimator and Cox proportional hazards model. ResultsMR revealed putative causal effects of seven CIs and eight BCs on FI. These CIs and BCs were integrated to establish a model for predicting FI. The predicted FI is significantly correlated with the observed FI (Pearson correlation coefficient = 0.660, P-value = 4.96 × 10-62). The prediction model indicated “usual walking pace” contributes the most to prediction. Patients who were predicted with high FI are in significantly higher risk of T2D (HR = 2.635, P < 2 × 10-16) and neurodegenerative diseases (HR = 2.307, P = 1.62 × 10-3) than other patients. ConclusionThis study supports associations of FI with CIs and BCs from genetic and phenotypic perspectives. The model that is developed by integrating easily collected CIs and BCs data in predicting FI has the potential to monitor disease risk.

Causal relationship between sarcopenia with osteoarthritis and the mediating role of obesity: a univariate, multivariate, two-step Mendelian randomization study

BackgroundRecent genetic evidence supports a causal role for sarcopenia in osteoarthritis, which may be mediated by the occurrence of obesity or changes in circulating inflammatory protein levels. Here, we leveraged publicly available genome-wide association study data to investigate the intrinsic causal relationship between sarcopenia, obesity, circulating inflammatory protein levels, and osteoarthritis.MethodsIn this study, we used Mendelian randomization analyses to explore the causal relationship between sarcopenia phenotypes (Appendicular lean mass [ALM], Low hand-grip strength [LHG], and usual walking pace [UWP]) and osteoarthritis (Knee osteoarthritis [KOA], and Hip osteoarthritis [HOA]). Univariable Mendelian randomization (UVMR) analyses were performed using the inverse variance weighted (IVW) method, MR-Egger, weighted median method, simple mode, and weighted mode, with the IVW method being the primary analytical technique. Subsequently, the independent causal effects of sarcopenia phenotype on osteoarthritis were investigated using multivariate Mendelian randomization (MVMR) analysis. To further explore the mechanisms involved, obesity and circulating inflammatory proteins were introduced as the mediator variables, and a two-step Mendelian randomization analysis was used to explore the mediating effects of obesity and circulating inflammatory proteins between ALM and KOA as well as the mediating proportions.ResultsUVMR analysis showed a causal relationship between ALM, LHG, UWP and KOA [(OR = 1.151, 95% CI: 1.087–1.218, P = 1.19 × 10–6, PFDR = 7.14 × 10–6) (OR = 1.215, 95% CI: 1.004–1.470; P = 0.046, PFDR = 0.055) (OR = 0.503, 95% CI: 0.292–0.867; P = 0.013, PFDR = 0.027)], and a causal relationship between ALM, UWP and HOA [(OR = 1.181, 95% CI: 1.103–1.265, P = 2.05 × 10–6, PFDR = 6.15 × 10–6) (OR = 0.438, 95% CI: 0.226–0.849, P = 0.014, PFDR = 0.022)]. In the MVMR analyses adjusting for confounders (body mass index, insomnia, sedentary behavior, and bone density), causal relationships were observed between ALM, LHG, UWP and KOA [(ALM: OR = 1.323, 95%CI: 1.224- 1.431, P = 2.07 × 10–12), (LHG: OR = 1.161, 95%CI: 1.044- 1.292, P = 0.006), (UWP: OR = 0.511, 95%CI: 0.290- 0.899, P = 0.020)], and between ALM and HOA (ALM: OR = 1.245, 95%CI: 1.149- 1.348, P = 7.65 × 10–8). In a two-step MR analysis, obesity was identified to play a potential mediating role in ALM and KOA (proportion mediated: 5.9%).ConclusionsThe results of this study suggest that decreased appendicular lean mass, grip strength, and walking speed increase the risk of KOA and decreased appendicular lean mass increases the risk of HOA in patients with sarcopenia in a European population. Obesity plays a mediator role in the occurrence of KOA due to appendicular lean body mass reduction.