Medicine (Northwest Academic Centre) - Theses

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Author: Zanker, Jesse Randall × Type: PhD thesis × Subject: Sarcopenia ×

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    Sarcopenia in Australia and New Zealand and the importance of muscle
    Zanker, Jesse Randall ( 2023-03)
    Abstract Background Sarcopenia is a condition of low muscle strength, low muscle mass and poor physical performance. Sarcopenia is highly prevalent in older adults, particularly among those with comorbidities such as frailty, or those living in residential aged care. Sarcopenia is associated with increased risk for falls, fractures, hospitalisation, institutionalisation and mortality, but remains under recognised and under treated. There is no universally accepted definition of sarcopenia which creates inconsistencies between and within regions and healthcare providers. The most recent and widely cited definitions of sarcopenia are the revised European Working Group for Sarcopenia in Older People (EWGSOP2), Sarcopenia Definitions and Outcomes Consortium (SDOC), and the revised Asian Working Group for Sarcopenia in Older People (AWGS2). The absence of a universal definition has hampered research progress and contributed to limited translation of sarcopenia knowledge to clinical practice. Additionally, the importance of low muscle mass and its contribution to negative outcomes in older people remains unclear, largely owing to disagreement around the techniques used to determine muscle quantity or quality. Furthermore, in Australia and New Zealand, there have been no regionally specific consumer-informed clinical guidelines to aid health professionals in caring for people with sarcopenia, or to guide research, which has limited knowledge translation. Aims To i) understand the impact of sarcopenia definitions on its prevalence and outcomes, ii) explore the role of an accurate measure of muscle mass on mobility and disability outcomes, and iii) establish consumer- and topic expert-informed evidence-based clinical and research sarcopenia guidelines for use in Australia and New Zealand. Methods Chapter 2 employed a narrative literature review approach to critically examine current literature and identify knowledge gaps. Chapters 3, 8 and 9 used variations of the modified Delphi method with consumer expert (Chapter 8) and topic expert (Chapters 3 and 9) participants to establish regionally specific operational definitions of sarcopenia in Australia and New Zealand, and present clinical and research sarcopenia guidelines. Chapters 4 to 7 employed either factor analysis or Classification and Regression Tree (CART) analysis to understand the prevalence of sarcopenia, and associations of muscle mass (and surrogate measures), muscle strength and physical performance with adverse outcomes in older adults. Chapter 4 applied factor analysis to the longitudinal Osteoporotic Fractures in Men Study (MrOS) to determine groupings and associations of muscle strength, physical performance, body composition and muscle mass with activities of daily living limitations and disability, and mobility disability. Chapter 5 applied CART to the MrOS study data to determine which muscle strength, physical performance, body composition and muscle mass measures predict incident mobility disability. Chapter 6 applied the CART methodology to a pooled, cross-sectional cohort of eight epidemiologic studies from Australia and New Zealand to determine optimal variables and cut points predicting slow walking speed (<0.8 m/s), and compared agreement between recent sarcopenia definitions. Chapter 7 applied the CART methodology to the Dubbo Osteoporosis Epidemiology Study (DOES2) to determine which baseline muscle strength, physical performance and body size and composition variables best predict incident mortality and falls, and prevalent slow walking speed (<0.8 m/s) in older women and men. Results Chapter 3 established consensus among topic experts that the original European Working Group for Sarcopenia in Older People (EWGSOP1) operational definition was recommended for Australia and New Zealand. Chapter 8 showed that people living with sarcopenia, their carers and healthcare consumers have different assessment and outcome priorities than sarcopenia topic experts. Chapter 9 produced 17 consensus statements on sarcopenia prevention, assessment and management in Australia and New Zealand, and established the EWGSOP2 sarcopenia as the preferred definition in the region. Chapters 4 and 5 demonstrated the importance of an accurate measure of muscle mass (D3Cr muscle mass) in predicting negative outcomes in older men. Chapter 4 showed that D3Cr muscle mass is strongly correlated with measures of muscle strength and physical performance, and combined these measures are associated with negative mobility and disability outcomes in older men. Chapter 5 found that D3Cr muscle mass is an important predictor of incident mobility disability in older men, in contrast to DXA-determined lean mass. Chapters 6 and 7 examined Australian and New Zealand older adults, demonstrating poor sarcopenia definition agreement (Chapter 6) and variable predictive ability of different measures of muscle strength and physical performance for mortality and falls in women and men (Chapter 7). Chapter 6 replicated the findings of the SDOC showing that hand grip strength (with body size adjustments) is the strongest predictor of prevalent slow walking speed (<0.8 m/s) and that the SDOC and EWGSOP2 sarcopenia definitions have poor agreement and produce different sarcopenia prevalence estimates. Chapter 7 found that age and walking speed adjusted for height were the most important predictors for mortality in women, and quadriceps strength (with adjustments) was the most important predictor for mortality in men. In both sexes, sit-to-stand test (with adjustments) was the most important predictor for incident falls, and timed-up-and-go test was the most important predictor for prevalent slow walking speed (<0.8 m/s). Chapter 10 critically discussed the findings, examined limitations, and outlined future directions. Conclusions This thesis demonstrated that i) different sarcopenia definitions and measures produce highly variable prevalence estimates and outcome predictions between women and men, ii) an accurate measure of muscle mass (D3Cr muscle mass) is a strong predictor of mobility and disability outcomes in older men, and iii) established consumer- and topic expert-informed sarcopenia guidelines in Australia and New Zealand. Further study is required to determine the role of the D3Cr method in clinical practice and to establish a global definition of sarcopenia.