Medicine (RMH) - Research Publications
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ItemPathophysiological Mechanisms Explaining the Association Between Low Skeletal Muscle Mass and Cognitive Function(OXFORD UNIV PRESS INC, 2022-10-06)Low skeletal muscle mass is associated with cognitive impairment and dementia in older adults. This review describes the possible underlying pathophysiological mechanisms: systemic inflammation, insulin metabolism, protein metabolism, and mitochondrial function. We hypothesize that the central tenet in this pathophysiology is the dysfunctional myokine secretion consequent to minimal physical activity. Myokines, such as fibronectin type III domain containing 5/irisin and cathepsin B, are released by physically active muscle and cross the blood-brain barrier. These myokines upregulate local neurotrophin expression such as brain-derived neurotrophic factor (BDNF) in the brain microenvironment. BDNF exerts anti-inflammatory effects that may be responsible for neuroprotection. Altered myokine secretion due to physical inactivity exacerbates inflammation and impairs muscle glucose metabolism, potentially affecting the transport of insulin across the blood-brain barrier. Our working model also suggests other underlying mechanisms. A negative systemic protein balance, commonly observed in older adults, contributes to low skeletal muscle mass and may also reflect deficient protein metabolism in brain tissues. As a result of age-related loss in skeletal muscle mass, decrease in the abundance of mitochondria and detriments in their function lead to a decrease in tissue oxidative capacity. Dysfunctional mitochondria in skeletal muscle and brain result in the excessive production of reactive oxygen species, which drives tissue oxidative stress and further perpetuates the dysfunction in mitochondria. Both oxidative stress and accumulation of mitochondrial DNA mutations due to aging drive cellular senescence. A targeted approach in the pathophysiology of low muscle mass and cognition could be to restore myokine balance by physical activity.
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ItemHandgrip strength rather than chair stand test should be used to diagnose sarcopenia in geriatric rehabilitation inpatients: REStORing health of acutely unwell adulTs (RESORT)(OXFORD UNIV PRESS, 2022-11-02)BACKGROUND: according to the revised sarcopenia definition proposed by the European Working Group on Sarcopenia in Older People (EWGSOP2) and revised definition of the Asian Working Group for Sarcopenia (AWGS2019), handgrip strength (HGS) and chair stand test (CST) can be used interchangeably as initial diagnostic measures. OBJECTIVE: to assess the agreement between sarcopenia prevalence, using either HGS or CST, and their association with adverse outcomes in geriatric rehabilitation inpatients. METHODS: REStORing health of acutely unwell adulTs is an observational, longitudinal cohort of geriatric rehabilitation inpatients. Cohen's kappa (κ) was used to assess the agreement between sarcopenia prevalence (no, probable and confirmed and severe sarcopenia) according to EWGSOP2 and AWGS2019 using either HGS or CST. Associations between HGS and CST and readmission, institutionalisation and mortality were assessed by binomial regression. RESULTS: patients (n = 1,250, 57% females) had a median age of 83.1 years (interquartile range: [77.5-88.3]). There was no agreement between probable sarcopenia prevalence using HGS or CST for EWGSOP2 and AWGS2019, respectively (HGS: 70.9% and 76.2%; CST: 95.5% and 98.4%; κ = 0.08 and 0.02). Agreement between confirmed and severe sarcopenia prevalence using either HGS or CST was strong to almost perfect. HGS was associated with 3-month institutionalisation and 3-month and 1-year mortality, whereas CST was not associated. CONCLUSIONS: HGS and CST cannot be used interchangeably as diagnostic measures for probable sarcopenia in geriatric rehabilitation inpatients. CST is not useful to predict adverse outcomes in geriatric rehabilitation inpatients.
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ItemValidation of a multi-frequency bioelectrical impedance analysis device for the assessment of body composition in older adults with type 2 diabetes(SPRINGERNATURE, 2022-10-20)BACKGROUND: Aging and type 2 diabetes (T2DM) are associated with an increased risk of sarcopenia. Diagnosis of sarcopenia is commonly done using dual-energy X-ray absorptiometry (DXA) in specialized settings. Another available method for assessing body composition is direct segmental multi-frequency bioelectrical impedance analysis (DSMF-BIA). Here, we examine the accuracy of a DSMF-BIA (InBody-770) for assessing body composition in older adults with T2DM when compared to DXA. METHODS: Eighty-four obese/overweight older adults (49 women, 71 ± 5 years) with T2DM who were recruited for the CEV-65 study and had both DSMF-BIA and DXA assessments at baseline were included. The analysis included Bland-Altman plots and intra class correlation coefficients. Sub-analyses were performed according to gender and following 10 weeks of interventions (diet, circuit training, and Empagliflozin). RESULTS: The leg lean mass results according to DSMF-BIA and DXA were 14.76 ± 3.62 kg and 15.19 ± 3.52 kg, respectively, with no difference between devices according to Bland-Altman analyses (p = 0.353). Assessment of appendicular skeletal mass index did not differ between DSMF-BIA and DXA (7.43 vs. 7.47 kg/m2; p = 0.84; ICC = 0.965, p < 0.0001; mean difference -0.068, p = 0.595). Gender and treatment interventions did not modify the accuracy of the DSMF-BIA when compared to DXA. CONCLUSIONS: In older adults with T2DM the degree of agreement between DSMF-BIA and DXA, was high, supporting the use of DSMF-BIA to measure muscle mass.
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ItemKnowledge of Nutrition and Physical Activity Guidelines is Not Associated with Physical Function in Dutch Older Adults Attending a Healthy Ageing Public Engagement Event(DOVE MEDICAL PRESS LTD, 2022)PURPOSE: Evidence-based guidelines on nutrition and physical activity are used to increase knowledge in order to promote a healthy lifestyle. However, actual knowledge of guidelines is limited and whether it is associated with health outcomes is unclear. PARTICIPANTS AND METHODS: This inception cohort study aimed to investigate the association of knowledge of nutrition and physical activity guidelines with objective measures of physical function and physical activity in community-dwelling older adults attending a public engagement event in Amsterdam, The Netherlands. Knowledge of nutrition and physical activity according to Dutch guidelines was assessed using customized questionnaires. Gait speed and handgrip strength were proxies of physical function and the Minnesota Leisure Time Physical Activity Questionnaire was used to assess physical activity in minutes/week. Linear regression analysis, stratified by gender and adjusted for age, was used to study the association between continuous and categorical knowledge scores with outcomes. RESULTS: In 106 older adults (mean age=70.1 SD=6.6, years) who were highly educated, well-functioning, and generally healthy, there were distinct knowledge gaps in nutrition and physical activity which did not correlate with one another (R2=0.013, p=0.245). Knowledge of nutrition or physical activity guidelines was not associated with physical function or physical activity. However, before age-adjustment nutrition knowledge was positively associated with HGS in males (B= 0.64 (95% CI: 0.05, 1.22)) and having knowledge above the median was associated with faster gait speed in females (B=0.10 (95% CI: 0.01, 0.19)). CONCLUSION: Our findings may represent a ceiling effect of the impact knowledge has on physical function and activity in the this high performing and educated population and that there may be other determinants of behavior leading to health status such as attitude and perception to consider in future studies.
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ItemIndividualised Nutritional Care for Disease-Related Malnutrition: Improving Outcomes by Focusing on What Matters to Patients(MDPI, 2022-09)Delivering care that meets patients' preferences, needs and values, and that is safe and effective is key to good-quality healthcare. Disease-related malnutrition (DRM) has profound effects on patients and families, but often what matters to patients is not captured in the research, where the focus is often on measuring the adverse clinical and economic consequences of DRM. Differences in the terminology used to describe care that meets patients' preferences, needs and values confounds the problem. Individualised nutritional care (INC) is nutritional care that is tailored to a patient's specific needs, preferences, values and goals. Four key pillars underpin INC: what matters to patients, shared decision making, evidence informed multi-modal nutritional care and effective monitoring of outcomes. Although INC is incorporated in nutrition guidelines and studies of oral nutritional intervention for DRM in adults, the descriptions and the degree to which it is included varies. Studies in specific patient groups show that INC improves health outcomes. The nutrition care process (NCP) offers a practical model to help healthcare professionals individualise nutritional care. The model can be used by all healthcare disciplines across all healthcare settings. Interdisciplinary team approaches provide nutritional care that delivers on what matters to patients, without increased resources and can be adapted to include INC. This review is of relevance to all involved in the design, delivery and evaluation of nutritional care for all patients, regardless of whether they need first-line nutritional care or complex, highly specialised nutritional care.
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ItemPredictors for the Transitions of Poor Clinical Outcomes Among Geriatric Rehabilitation Inpatients(ELSEVIER SCIENCE INC, 2022-11)OBJECTIVE: To investigate the associations of morbidity burden and frailty with the transitions between functional decline, institutionalization, and mortality. DESIGN: REStORing health of acutely unwell adulTs (RESORT) is an ongoing observational, longitudinal inception cohort and commenced on October 15, 2017. Consented patients were followed for 3 months postdischarge. SETTING AND PARTICIPANTS: Consecutive geriatric rehabilitation inpatients admitted to geriatric rehabilitation wards. METHODS: Patients' morbidity burden was assessed at admission using the Charlson Comorbidity Index (CCI) and Cumulative Illness Rating Scale (CIRS). Frailty was assessed using the Clinical Frailty Scale (CFS) and modified Frailty Index based on laboratory tests (mFI-lab). A multistate model was applied at 4 time points: 2 weeks preadmission, admission, and discharge from geriatric rehabilitation and 3 months postdischarge, with the following outcomes: functional decline, institutionalization, and mortality. Cox proportional hazards regression was applied to investigate the associations of morbidity burden and frailty with the transitions between outcomes. RESULTS: The 1890 included inpatients had a median age of 83.4 (77.6-88.4) years, and 56.3% were female. A higher CCI score was associated with a greater risk of transitions from preadmission and declined functional performance to mortality [hazard ratio (HR) 1.28, 95% CI 1.03-1.59; HR 1.32, 95% CI 1.04-1.67]. A higher CIRS score was associated with a higher risk of not recovering from functional decline (HR 0.80, 95% CI 0.69-0.93). A higher CFS score was associated with a greater risk of transitions from preadmission and declined functional performance to institutionalization (HR 1.28, 95% CI 1.10-1.49; HR 1.23, 95% CI 1.04-1.44) and mortality (HR 1.12, 95% CI 1.01-1.33; HR 1.11, 95% CI 1.003-1.31). The mFI-lab was not associated with any of the transitions. None of the morbidity measures or frailty assessment tools were associated with the transitions from institutionalization to other outcomes. CONCLUSIONS AND IMPLICATIONS: This study demonstrates that greater frailty severity, assessed using the CFS, is a significant risk factor for poor clinical outcomes and demonstrates the importance of implementing it in the geriatric rehabilitation setting.
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ItemThe Association of Changes in Physical Performance During Geriatric Inpatient Rehabilitation With Short-Term Hospital Readmission, Institutionalization, and Mortality: RESORT(ELSEVIER SCIENCE INC, 2022-11)OBJECTIVES: Geriatric inpatient rehabilitation aims to restore function, marked by physical performance, to enable patients to return and remain home after hospitalization. However, after discharge some patients are soon readmitted, institutionalized, or may die. Whether changes in physical performance during geriatric rehabilitation are associated with these short-term adverse outcomes is unknown. This study aimed to determine the association of changes in physical performance during geriatric inpatient rehabilitation with short-term adverse outcomes. DESIGN: Observational longitudinal study. SETTING AND PARTICIPANTS: Geriatric rehabilitation inpatients of the REStORing health of acutely unwell adulTs (RESORT) cohort study of the Royal Melbourne Hospital (Melbourne, Australia) were included. METHODS: The change from admission to discharge in the Short Physical Performance Battery (SPPB) score, balance, gait speed (GS), chair stand test (CST), and hand grip strength (HGS) were calculated and analyzed using logistic regression analysis with readmission, incidence of institutionalization, and mortality, and ≥1 adverse outcome within 3 months postdischarge. RESULTS: Of 693 inpatients, 11 died during hospitalization and 572 patients (mean age 82.6 ± 7.6 years, 57.9% female) had available physical performance data. Within 3 months postdischarge, 47.3% of patients had ≥1 adverse outcome: readmission was 20.8%, institutionalization was 26.6%, and mortality was 7.9%. Improved SPPB score, balance, GS, CST, and HGS were associated with lower odds of institutionalization and mortality. Improved GS was additionally associated with lower odds of readmission [odds ratio (OR) 0.35, 95% CI 0.16-0.79]. CST score had the largest effect, with a 1-point increase associating with 40% lower odds of being institutionalized (OR 0.60, 95% CI 0.42-0.86), 52% lower odds of mortality (OR 0.48, 95% CI 0.29-0.81), and a 24% lower odds of ≥1 adverse outcome (OR 0.76, 95% CI 0.59-0.97). CONCLUSIONS AND IMPLICATIONS: Improvement in physical performance was associated with lower odds of short-term institutionalization and mortality indicating the prognostic value of physical performance improvement during geriatric inpatient rehabilitation.
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ItemScreening, Diagnosis and Management of Sarcopenia and Frailty in Hospitalized Older Adults: Recommendations from the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Expert Working Group(ELSEVIER SCIENCE INC, 2022-06)Sarcopenia and frailty are highly prevalent conditions in older hospitalized patients, which are associated with a myriad of adverse clinical outcomes. This paper, prepared by a multidisciplinary expert working group from the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR), provides an up-to-date overview of current evidence and recommendations based on a narrative review of the literature for the screening, diagnosis, and management of sarcopenia and frailty in older patients within the hospital setting. It also includes suggestions on potential pathways to implement change to encourage widespread adoption of these evidence-informed recommendations within hospital settings. The expert working group concluded there was insufficient evidence to support any specific screening tool for sarcopenia and recommends an assessment of probable sarcopenia/sarcopenia using established criteria for all older (≥65 years) hospitalized patients or in younger patients with conditions (e.g., comorbidities) that may increase their risk of sarcopenia. Diagnosis of probable sarcopenia should be based on an assessment of low muscle strength (grip strength or five times sit-to-stand) with sarcopenia diagnosis including low muscle mass quantified from dual energy X-ray absorptiometry, bioelectrical impedance analysis or in the absence of diagnostic devices, calf circumference as a proxy measure. Severe sarcopenia is represented by the addition of impaired physical performance (slow gait speed). All patients with probable sarcopenia or sarcopenia should be investigated for causes (e.g., chronic/acute disease or malnutrition), and treated accordingly. For frailty, it is recommended that all hospitalized patients aged 70 years and older be screened using a validated tool [Clinical Frailty Scale (CFS), Hospital Frailty Risk Score, the FRAIL scale or the Frailty Index]. Patients screened as positive for frailty should undergo further clinical assessment using the Frailty Phenotype, Frailty Index or information collected from a Comprehensive Geriatric Assessment (CGA). All patients identified as frail should receive follow up by a health practitioner(s) for an individualized care plan. To treat older hospitalized patients with probable sarcopenia, sarcopenia, or frailty, it is recommended that a structured and supervised multi-component exercise program incorporating elements of resistance (muscle strengthening), challenging balance, and functional mobility training be prescribed as early as possible combined with nutritional support to optimize energy and protein intake and correct any deficiencies. There is insufficient evidence to recommend pharmacological agents for the treatment of sarcopenia or frailty. Finally, to facilitate integration of these recommendations into hospital settings organization-wide approaches are needed, with the Spread and Sustain framework recommended to facilitate organizational culture change, with the help of 'champions' to drive these changes. A multidisciplinary team approach incorporating awareness and education initiatives for healthcare professionals is recommended to ensure that screening, diagnosis and management approaches for sarcopenia and frailty are embedded and sustained within hospital settings. Finally, patients and caregivers' education should be integrated into the care pathway to facilitate adherence to prescribed management approaches for sarcopenia and frailty.
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ItemImpact of adherence to a lifestyle-integrated programme on physical function and behavioural complexity in young older adults at risk of functional decline: a multicentre RCT secondary analysis(BMJ PUBLISHING GROUP, 2022-10)CONTEXT: Long-term adherence to physical activity (PA) interventions is challenging. The Lifestyle-integrated Functional Exercise programmes were adapted Lifestyle-integrated Functional Exercise (aLiFE) to include more challenging activities and a behavioural change framework, and then enhanced Lifestyle-integrated Functional Exercise (eLiFE) to be delivered using smartphones and smartwatches. OBJECTIVES: To (1) compare adherence measures, (2) identify determinants of adherence and (3) assess the impact on outcome measures of a lifestyle-integrated programme. DESIGN, SETTING AND PARTICIPANTS: A multicentre, feasibility randomised controlled trial including participants aged 61-70 years conducted in three European cities. INTERVENTIONS: Six-month trainer-supported aLiFE or eLiFE compared with a control group, which received written PA advice. OUTCOME MEASURES: Self-reporting adherence per month using a single question and after 6-month intervention using the Exercise Adherence Rating Scale (EARS, score range 6-24). Treatment outcomes included function and disability scores (measured using the Late-Life Function and Disability Index) and sensor-derived physical behaviour complexity measure. Determinants of adherence (EARS score) were identified using linear multivariate analysis. Linear regression estimated the association of adherence on treatment outcome. RESULTS: We included 120 participants randomised to the intervention groups (aLiFE/eLiFE) (66.3±2.3 years, 53% women). The 106 participants reassessed after 6 months had a mean EARS score of 16.0±5.1. Better adherence was associated with lower number of medications taken, lower depression and lower risk of functional decline. We estimated adherence to significantly increase basic lower extremity function by 1.3 points (p<0.0001), advanced lower extremity function by 1.0 point (p<0.0001) and behavioural complexity by 0.008 per 1.0 point higher EARS score (F(3,91)=3.55, p=0.017) regardless of group allocation. CONCLUSION: PA adherence was associated with better lower extremity function and physical behavioural complexity. Barriers to adherence should be addressed preintervention to enhance intervention efficacy. Further research is needed to unravel the impact of behaviour change techniques embedded into technology-delivered activity interventions on adherence. TRIAL REGISTRATION NUMBER: NCT03065088.
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ItemTargeting Impaired Nutrient Sensing via the Glycogen Synthase Kinase-3 Pathway With Therapeutic Compounds to Prevent or Treat Dementia: A Systematic Review(FRONTIERS MEDIA SA, 2022-07-18)Background: Dementia is a global challenge with 10 million individuals being diagnosed every year. Currently, there are no established disease-modifying treatments for dementia. Impaired nutrient sensing has been implicated in the pathogenesis of dementia. Compounds that inhibit the glycogen synthase kinase-3 (GSK3) pathway have been investigated as a possible treatment to attenuate the progression of the disease, particularly the suppression of the hyper-phosphorylation process of the tau protein. Aims: Systematically summarizing compounds which have been tested to inhibit the GSK3 pathway to treat cognitive impairment and dementia. Methods: PubMed, Embase and Web of Science databases were searched from inception until 28 July 2021 for articles published in English. Interventional animal studies inhibiting the GSK3 pathway in Alzheimer's disease (AD), Parkinson's dementia, Lewy body dementia, vascular dementia, mild cognitive impairment (MCI) and normal cognitive ageing investigating the change in cognition as the outcome were included. The Systematic Review Centre for Laboratory animal Experimentation's risk of bias tool for animal studies was applied. Results: Out of 4,154 articles, 29 described compounds inhibiting the GSK3 pathway. All studies were based on animal models of MCI, AD or normal cognitive ageing. Thirteen out of 21 natural compounds and five out of nine synthetic compounds tested in MCI and dementia animal models showed an overall positive effect on cognition. No articles reported human studies. The risk of bias was largely unclear. Conclusion: Novel therapeutics involved in the modulation of the GSK3 nutrient sensing pathway have the potential to improve cognitive function. Overall, there is a clear lack of translation from animal models to humans.