Iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation (IDEAL-IQ), a quantitative 6-point Dixon magnetic resonance imaging (MRI) sequence, has been increasingly used for quantifying muscle fat fraction (FF) in neuromuscular disorders. However, its utility for correlating FF with disease severity and mapping spatiotemporal disease progression in Duchenne muscular dystrophy (DMD) requires further investigation.
In 10 patients with dystrophinopathies (seven DMD and three BMD) we correlated the muscle FF with the histopathological fatty infiltration. IDEAL-IQ MRI images of 19 individual lower limb muscles were acquired from 133 DMD patients and 41 healthy controls. Ambulatory function tests, including three timed function tests (TFTs) and North Star Ambulatory Assessment (NSAA), were performed. We investigated the spatial distribution of fatty infiltration across five axial MRI slices. Disease progression patterns were analysed using a piecewise linear model and a normal cumulative distribution function model.
A significant positive correlation between muscle FF on MRI and histopathologic fatty infiltration was observed (ρ = 0.98, p < 0.001). A mild to moderate correlation was noted for the FF of 19 individual muscles, excluding the sartorius and gracilis muscles, with TFTs (ρ = 0.27–0.60, p < 0.001) and NSAA (ρ = −0.32–−0.73, p < 0.001). All the eight individual muscles, except the tibialis posterior muscle, showed an inhomogeneous fatty infiltration pattern with higher FF in muscle ends compared to bellies. Thigh muscle FF aligned well with both piecewise linear and sigmoidal models, showing non-linear increases with disease duration. The piecewise linear model identified an average inflection point for thigh muscle FF at 7.3 (range, 5.2–7.6) years, with average annual FF increase of 1.7% before and 6.7% after the point in DMD. The average μ of DMD patients for thigh muscles was 11.4 years (±2.8), occurring 7.6 years earlier compared to BMD patients.
Our study demonstrates a significant relationship between muscle FF on IDEAL-IQ MRI and histopathologic muscle fatty infiltration, as well as ambulatory clinical function in DMD. DMD patients exhibit a distinct and inhomogeneous fat infiltration pattern of lower limb muscles.
Chronic exposure to low levels of lead (Pb) remains a widespread public health issue, especially among older adults. While its neurotoxic and cardiovascular effects are well recognized, its potential role in accelerating age-related musculoskeletal decline is less understood. Emerging evidence suggests Pb may contribute to sarcopenia, but epidemiological data, especially regarding the most informative biomarkers of exposure, are limited.
We analysed data from 11 842 participants aged ≥ 60 years across four population-based studies (NHANES III, NHANES 1999–2006, NHANES 2011–2012 and Seniors-ENRICA-2). Sarcopenia indicators included muscle strength (grip strength and chair stand test), muscle mass (dual-energy X-ray absorptiometry, calf circumference and arm circumference) and muscle function (gait speed and Short Physical Performance Battery scores). Sarcopenia was defined in the Seniors-ENRICA-2 using the European Working Group on Sarcopenia in Older People 2 criteria. Associations between Pb exposure (serum and whole blood) and sarcopenia indicators were estimated using multivariable regression and meta-analyses.
Pb levels were associated with residential environmental exposures such as traffic proximity, industrial emissions and soil contamination, explaining approximately 11% of variability in whole blood Pb and 9% in serum Pb. Both whole blood and serum Pb showed dose-dependent inverse associations with muscle sarcopenia indicators, including measures of strength, mass and function. Associations with lower limb outcomes were generally stronger for serum Pb compared with whole blood Pb. An interquartile range increase in serum Pb was associated with a 1.33-fold increase in the odds of confirmed or severe sarcopenia (95% CI: 1.02, 1.70), compared with a 1.20-fold increase for whole blood Pb (95% CI: 1.06, 1.36).
Environmental Pb exposure is associated with detrimental effects on musculoskeletal health and contributes to sarcopenia in older adults. Serum Pb may be a more sensitive biomarker of musculoskeletal aging than whole blood Pb and should be considered in future research and surveillance strategies.
Frailty is a prevalent syndrome in older adults and is associated with increased vulnerability to adverse health outcomes. Growth differentiation factor 15 (GDF-15), a cytokine involved in mitochondrial dysfunction and inflammation, has been proposed as a potential biomarker for age-related conditions. Evidence on the association between GDF-15 and frailty in older adults is limited. This study explores the relationship between plasma GDF-15 levels and frailty onset in community-dwelling older adults.
A secondary analysis was performed on 1096 participants (mean age = 75.2 ± 4.5 years; 64.5% women) from the Multidomain Alzheimer Prevention Trial (MAPT). Plasma GDF-15 levels were measured at year 1. Frailty was assessed using the Fried phenotype. Logistic regression was used to examine cross-sectional associations between GDF-15 and frailty, while mixed effects logistic regression or Cox proportional hazards models assessed longitudinal associations over a 4-year follow-up.
Higher plasma GDF-15 levels (both as continuous and categorical) were cross-sectionally associated with frailty (high vs. low GDF-15: OR = 3.56, 95% CI = 1.58–8.03). Longitudinally, very high GDF-15 levels predicted an increased risk of incident frailty (HR = 1.69, 95% CI = 1.03–2.78).
Elevated plasma GDF-15 levels were associated with frailty in older adults, suggesting its potential as a biomarker for increased vulnerability and an indicator of increased risk over time. Our results support a pleiotropic role of GDF-15, with low physiological levels not contributing to frailty development.
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