Medicine (Western Health) - Research Publications

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    Muscle and Bone: An Indissoluble Union
    Kirk, B ; Duque, G (WILEY, 2022-07)
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    Handgrip strength is associated with learning and verbal fluency in older men without dementia: insights from the NHANES
    Prokopidis, K ; Giannos, P ; Ispoglou, T ; Kirk, B ; Witard, OC ; Dionyssiotis, Y ; Scott, D ; Macpherson, H ; Duque, G ; Isanejad, M (SPRINGER, 2023-04)
    Low handgrip strength, a hallmark measure of whole-body strength, has been linked with greater odds of cognitive decline and dementia; however, conflicting findings, which could be due to population characteristics and choice of tools, such for the assessment of handgrip strength and cognitive function domains, also exist. Therefore, we examined the relationship of handgrip strength with a comprehensive list of tests to assess domains of cognitive function using a representative sample of US older men and women without neurodegenerative disorders such as dementia. We analyzed cross-sectional data from the US National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014, with a study cohort of 777 older adults (380 men and 397 women) above 60 years of age. Handgrip strength was assessed using a handgrip dynamometer, while cognitive function was assessed through the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Learning Test (WLLT), Word List Recall Test (WLRT), Intrusion Word Count Test (WLLT-IC and WLRT-IC), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Sex-stratified multiple linear regression analyses were performed upon covariate adjustment for age, ethnicity, socio-economic status, education, medical history, body mass index, physical activity, energy, protein, and alcohol intake. Maximal handgrip strength was positively associated with cognitive function scores, including CERAD WLLT (P = 0.009, R2 = 0.146) and AFT (P = 0.022, R2 = 0.024) in older men, but not in women (CERAD WLLT: P = 0.253, AFT: P = 0.370). No significant associations with CERAD WLLRT (men: P = 0.057, women: P = 0.976), WLLT-IC (men: P = 0.671, women: P = 0.869), WLLRT-IC (men: P = 0.111, women: P = 0.861), and DSST (men: P = 0.108, women: P = 0.091) were observed. Dose-response curves exhibited a prominent linear relationship between all significant associations after covariate adjustment, with no indication of a plateau in these relationships. In conclusion, higher handgrip strength was independently associated with better learning ability for novel verbal information and verbal fluency in US men over the age of 60 and without dementia. Longitudinal studies are required to confirm whether muscle strength independently predicts cognitive function changes in older adults in a sex-specific manner, and whether this connection is affirmed to the possibility of reverse causation due to declines in physical activity levels in the preclinical phase of dementia.
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    Defining terms commonly used in sarcopenia research: a glossary proposed by the Global Leadership in Sarcopenia (GLIS) Steering Committee
    Cawthon, PM ; Visser, M ; Arai, H ; Avila-Funes, JA ; Barazzoni, R ; Bhasin, S ; Binder, E ; Bruyere, O ; Cederholm, T ; Chen, L-K ; Cooper, C ; Duque, G ; Fielding, RA ; Guralnik, J ; Kiel, DP ; Kirk, B ; Landi, F ; Sayer, AA ; Von Haehling, S ; Woo, J ; Cruz-Jentoft, AJ (SPRINGER, 2022-12)
    METHODS: The aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings. The Global Leadership Initiative in Sarcopenia (GLIS) aims to bring together leading investigators in sarcopenia research to develop a single definition that can be utilized worldwide; work on a global definition of sarcopenia is ongoing. The first step of GLIS is to develop the common terminology, or a glossary, that will facilitate agreement on a global definition of sarcopenia as well as interpretation of clinical and research findings. RESULTS: Several terms that are commonly used in sarcopenia research are defined, including self-reported measures of function and ability; objective physical performance tests; and measures related to muscle function and size. CONCLUSION: As new methods and technologies are developed, these definitions may be expanded or refined over time. Our goal is to promote this common language to describe sarcopenia and its components in clinical and research settings in order to increase clinical awareness and research interest in this important condition. We hope that the use of common terminology in sarcopenia research will increase understanding of the concept and improve communication around this important age-related condition.
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    Relationship Between Plasma Homocysteine and Bone Density, Lean Mass, Muscle Strength and Physical Function in 1480 Middle-Aged and Older Adults: Data from NHANES
    Kositsawat, J ; Vogrin, S ; French, C ; Gebauer, M ; Candow, DG ; Duque, G ; Kirk, B (SPRINGER, 2023-01)
    Hyperhomocysteinemia induces oxidative stress and chronic inflammation (both of which are catabolic to bone and muscle); thus, we examined the association between homocysteine and body composition and physical function in middle-aged and older adults. Data from the National Health and Nutrition Examination Survey was used to build regression models. Plasma homocysteine (fluorescence immunoassay) was used as the exposure and bone mineral density (BMD; dual-energy X-ray absorptiometry; DXA), lean mass (DXA), knee extensor strength (isokinetic dynamometer; newtons) and gait speed (m/s) were used as outcomes. Regression models were adjusted for confounders (age, sex, race/Hispanic origin, height, fat mass %, physical activity, smoking status, alcohol intakes, cardiovascular disease, diabetes, cancer and vitamin B12). All models accounted for complex survey design by using sampling weights provided by NHANES. 1480 adults (median age: 64 years [IQR: 56, 73]; 50.3% men) were included. In multivariable models, homocysteine was inversely associated with knee extensor strength (β = 0.98, 95% CI 0.96, 0.99, p = 0.012) and gait speed (β = 0.85, 95% CI 0.78, 0.94, p = 0.003) and borderline inversely associated with femur BMD (β = 0.84, 95% CI 0.69, 1.03, p = 0.086). In the sub-group analysis of older adults (≥ 65 years), homocysteine was inversely associated with gait speed and femur BMD (p < 0.05) and the slope for knee extensor strength and whole-body BMD were in the same direction. No significant associations were observed between homocysteine and total or appendicular lean mass in the full or sub-group analysis. We found inverse associations between plasma homocysteine and muscle strength/physical function, and borderline significant inverse associations for femur BMD.
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    Effects of 3 months of multi-nutrient supplementation on the immune system and muscle and respiratory function of older adults in aged care (The Pomerium Study): protocol for a randomised controlled trial
    Al Saedi, A ; Kirk, B ; Iuliano, S ; Zanker, J ; Vogrin, S ; Jayaram, L ; Thomas, S ; Golding, C ; Navarro-Perez, D ; Marusic, P ; Leng, S ; Nanan, R ; Duque, G (BMJ PUBLISHING GROUP, 2022-05)
    INTRODUCTION: Immunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with SARS-CoV-2 (COVID-19), which disproportionately impact older adults, particularly those in residential aged care facilities. Inadequate nutrient intakes associated with impaired immunity, respiratory and muscle function are likely to augment the effects of immunosenescence. In this study, we test whether the impact of inadequate nutrition can be reversed using multi-nutrient supplementation, consequently enhancing vaccine responses, reducing the risk of viral infections and improving respiratory and muscle function. METHODS AND ANALYSIS: The Pomerium Study is a 3-month, single-blind, randomised, controlled trial testing the effects of two daily servings of an oral multi-nutrient supplement (330 kcal, 20 g protein, 1.5 g calcium 3-hydroxy-3-methylbutyrate monohydrate (CaHMB), 449 mg calcium, 500 IU vitamin D3 and 25 vitamins and minerals) on the immune system and muscle and respiratory function of older adults in aged care in Melbourne, Australia. 160 older adults (≥75 years old) will be recruited from aged care facilities and randomised to treatment (multi-nutrient supplement) or control (usual care). The primary outcome is a change in T-cell subsets CD8 + and CD28null counts at months 1 and 3. Secondary outcomes measured at baseline and month 3 are multiple markers of immunosenescence (also at 1 month), body composition (bioimpedance), handgrip strength (dynamometer), physical function (short physical performance battery), respiratory function (spirometry) and quality of life (EQ-5D-5L). Incidence and complications of COVID-19 and/or viral infections (ie, hospitalisation, complications or death) will be recorded throughout the trial, including 3 months after supplementation is ceased. ETHICS AND DISSEMINATION: This study was approved by Melbourne Health Human Research Ethics Committee (Ref No. HREC/73985/MH-2021, ERM Ref No. RMH73985, Melbourne Health Site Ref No. 2021.115). Written informed consent will be obtained from participants. Results will be published in peer-reviewed journals and made available to key aged care stakeholders, including providers, residents, and government bodies. TRIAL REGISTRATION NUMBER: ACTRN12621000420842.
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    The prevention of osteoporosis and sarcopenia in older adults
    Coll, PP ; Phu, S ; Hajjar, SH ; Kirk, B ; Duque, G ; Taxel, P (WILEY, 2021-05)
    Osteoporosis and sarcopenia are common in older adults. Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Bone fractures can result in changes in posture, pain, the need for surgical repair and functional impairment. Sarcopenia is the progressive and generalized loss of skeletal muscle mass, strength and/or physical performance. Older adults with sarcopenia experience increased risk of frailty, disability, hospitalizations, mortality, and a reduced quality of life. In this narrative review we provide guidance regarding the prevention of both osteoporosis and sarcopenia, including interventions that prevent both conditions from occurring, recommended screening and treatment to prevent progression.
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    Leucine-enriched whey protein supplementation, resistance-based exercise, and cardiometabolic health in older adults: a randomized controlled trial
    Kirk, B ; Mooney, K ; Vogrin, S ; Jackson, M ; Duque, G ; Khaiyat, O ; Amirabdollahian, F (WILEY, 2021-12)
    BACKGROUND: Increasing protein intake (above the Recommended Dietary Amount) alone or with resistance-based exercise is suggested to improve cardiometabolic health; however, randomized controlled trials (RCTs) are needed to confirm this. METHODS: The Liverpool Hope University-Sarcopenia Aging Trial (LHU-SAT) was a 16 week RCT (ClinicalTrials.gov Identifier: NCT02912130) of 100 community-dwelling older adults [mean age: 68.73 ± 5.80 years, body mass index: 27.06 ± 5.18 kg/m2 (52% women)] who were randomized to four independent groups [Control (C), Exercise (E), Exercise + Protein (EP), Protein (P)]. E and EP completed supervised and progressive resistance-based exercise (resistance exercise: two times per week, functional circuit exercise: once per week), while EP and P were supplemented with a leucine-enriched whey protein drink (three times per day) based on individual body weight (0.50 g/kg/meal, 1.50 g/kg/day). Outcome measures including arterial stiffness (pulse wave velocity), fasting plasma/serum biomarkers [glucose/glycated haemoglobin, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, insulin, resistin, leptin, adiponectin, C-reactive protein, tumour necrosis factor-alpha, interleukin-6, cystatin-C, & ferritin], insulin resistance (HOMA-IR), and kidney function (eGFR) were measured before and after intervention. RESULTS: Total protein intake (habitual diet plus supplementation) increased to 1.55 ± 0.69 g/kg/day in EP and to 1.93 ± 0.72 g/kg/day in P, and remained significantly lower (P < 0.001) in unsupplemented groups (E: 1.08 ± 0.33 g/kg/day, C: 1.00 ± 0.26 g/kg/day). At 16 weeks, there was a group-by-time interaction whereby absolute changes in LDL-cholesterol were lower in EP [mean difference: -0.79 mmol/L, 95% confidence interval (CI): -1.29, -0.28, P = 0.002] and P (mean difference: -0.76 mmol/L, 95% CI: -1.26, -0.26, P = 0.003) vs. C. Serum insulin also showed group-by-time interactions at 16 weeks whereby fold changes were lower in EP (mean difference: -0.40, 95% CI: -0.65, -0.16, P = 0.001) and P (mean difference: -0.32, 95% CI: -0.56, -0.08, P = 0.009) vs. C, and fold changes in HOMA-IR improved in EP (mean difference: -0.37, 95% CI: -0.64, -0.10, P = 0.007) and P (mean difference: -0.27, 95% CI: -0.53, -0.00, P = 0.048) vs. C. Serum resistin declined in P only (group-by-time interaction at 16 weeks: P = 0.009). No other interactions were observed in outcome measures (P > 0.05), and kidney function (eGFR) remained unaltered. CONCLUSIONS: Sixteen weeks of leucine-enriched whey protein supplementation alone and combined with resistance-based exercise improved cardiometabolic health markers in older adults.
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    International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines
    Izquierdo, M ; Merchant, RA ; Morley, JE ; Anker, SD ; Aprahamian, I ; Arai, H ; Aubertin-Leheudre, M ; Bernabei, R ; Cadore, EL ; Cesari, M ; Chen, L-K ; de Souto Barreto, P ; Duque, G ; Ferrucci, L ; Fielding, RA ; Garcia-Hermoso, A ; Gutierrez-Robledo, LM ; Harridge, SDR ; Kirk, B ; Kritchevsky, S ; Landi, F ; Lazarus, N ; Martin, FC ; Marzetti, E ; Pahor, M ; Ramirez-Velez, R ; Rodriguez-Manas, L ; Rolland, Y ; Ruiz, JG ; Theou, O ; Villareal, DT ; Waters, DL ; Won, CW ; Woo, J ; Vellas, B ; Singh, MF (SPRINGER FRANCE, 2021-07)
    The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.
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    EFFECT OF DENOSUMAB ON FALLS, MUSCLE STRENGTH, AND FUNCTION IN COMMUNITY-DWELLING OLDER ADULTS
    Phu, S ; Hassan, EB ; Vogrin, S ; Kirk, B ; Duque, G (WILEY, 2019-12)
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    Body composition reference ranges in community-dwelling adults using dual-energy X-ray absorptiometry: the Australian Body Composition (ABC) Study
    Kirk, B ; Bani Hassan, E ; Brennan-Olsen, S ; Vogrin, S ; Bird, S ; Zanker, J ; Phu, S ; Meerkin, JD ; Heymsfield, SB ; Duque, G (WILEY, 2021-08)
    BACKGROUND: Reference ranges for lean mass (LM) and fat mass (FM) are essential in identifying soft tissue disorders; however, no such reference ranges exist for the most commonly used Hologic dual-energy X-ray absorptiometry (DXA) machine in Australia. METHODS: Cross-sectional study of community-dwelling adults (aged 18-88 years) who underwent a Hologic DXA scan at one of three commercialized densitometry centres in Australia. Age-specific and sex-specific percentile curves were generated for LM [LM, appendicular lean mass (ALM), ALM adjusted for height squared (ALM/h2 ), and ALM adjusted for body mass index (ALM/BMI)] and FM [FM, FM adjusted for height squared (FM/h2 ), appendicular fat mass, and android and gynoid fat] parameters using the LMS statistical method. Cutpoints equivalent to T-scores of -1, -2, and -2.5 standard deviations below the young mean reference group (20-29 years) were also generated for LM parameters. RESULTS: A total of 15 479 community-dwelling adults (54% men) with a median age of 33 years (interquartile range: 28, 42) were included. LM, ALM, and ALM/h2 remained stable until age 50, after which these parameters started to decline in both sexes. Compared with age 50, median percentiles of LM, ALM, and ALM/h2 declined by -5.9 kg, -3.7 kg, and -0.86 kg/m2 in men and by -2.5 kg, -1.8 kg, and -0.10 kg/m2 in women at age 70, respectively. Adjusting ALM for BMI (rather than height squared) resulted in different trends, with ALM/BMI decreasing from as early as age 20. Compared with age 20, median percentiles of ALM/BMI at age 40 declined by -0.10 kg/kg/m2 in men and by -0.06 kg/kg/m2 in women; and at age 70, ALM/BMI declined by -0.25 kg/kg/m2 in men and by -0.20 kg/kg/m2 in women. Cutpoints equivalent to T-scores of -1, -2, and -2.5 standard deviations for ALM/BMI were 1.01, 0.86, and 0.77 kg/kg/m2 in men and 0.70, 0.59, and 0.53 kg/kg/m2 in women, respectively. All FM parameters progressively increased from age 20 and continued up until age 70. CONCLUSIONS: We developed reference ranges for LM and FM parameters from Hologic DXA machines in a large cohort of Australian adults, which will assist researchers and clinicians in identifying soft tissue disorders such as obesity, sarcopenia, and cachexia.