Medicine (RMH) - Research Publications
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ItemPatterns of Objectively Measured Sedentary Behavior and Physical Activity and Their Association with Changes in Physical and Functional Performance in Geriatric Rehabilitation Inpatients(ELSEVIER SCIENCE INC, 2023-05)OBJECTIVES: To examine whether The Ending PyJama (PJ) Paralysis campaign, focused on increasing in-hospital physical activity, affects objectively measured sedentary behavior and physical activity patterns and if these are associated with changes in physical and functional performance in geriatric rehabilitation inpatients. DESIGN: Quasi-experimental study. SETTING AND PARTICIPANTS: Within the REStORing health of acutely unwell adulTs (RESORT) observational, longitudinal cohort of geriatric rehabilitation inpatients, the Ending PJ Paralysis campaign was implemented on 2 out of 4 wards. METHODS: Objectively measured sedentary behavior and physical activity were measured by an inertial sensor (ActivPAL4) for 1 week, comparing control (non-PJ) and intervention (PJ) groups using linear mixed models. Mean sedentary behavior and physical activity measures and their association with physical and functional performance changes were investigated by linear regression analyses, stratified by low vs high performance at admission using the median as a cut-off. RESULTS: A total of 145 (n = 68 non-PJ and n = 77 PJ) inpatients with a mean age of 83.0 (7.7) years (55.9% female inpatients) were included. The median nonupright time was 23.1 [22.1-23.6] and 23.0 [21.8-23.6] hours/day for non-PJ and PJ groups, respectively. Objectively measured sedentary behavior and physical activity measures did not significantly change over measurement days and were independent of the Ending PJ Paralysis campaign. For inpatients with low performance at admission, lower sedentary behavior [B(SE) -0.013 (0.005) to -0.157 (0.045), P < .01] and higher physical activity [B(SE) 0.033 (0.007) to 0.814 (0.200), P < .01] measures were associated with improved physical performance. In addition, lower sedentary behaviour [B(SE) = -0.058 (0.024), P < .05 and higher physical activity [B (SE) 0.060 (0.024) to 0.683 (0.182), P < .05] were associated with improved instrumental functional performance. CONCLUSIONS AND IMPLICATIONS: In geriatric rehabilitation inpatients, the Ending PJ Paralysis campaign did not affect objectively measured sedentary behavior and physical activity patterns. Lower mean sedentary behaviour and higher physical activity measures were associated with improved physical and functional performance in inpatients with low performance.
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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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ItemThe efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial(SPRINGER, 2023-02)In animal studies, β-nicotinamide mononucleotide (NMN) supplementation increases nicotinamide adenine dinucleotide (NAD) concentrations and improves healthspan and lifespan with great safety. However, it is unclear if these effects can be transferred to humans. This randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial included 80 middle-aged healthy adults being randomized for a 60-day clinical trial with once daily oral dosing of placebo, 300 mg, 600 mg, or 900 mg NMN. The primary objective was to evaluate blood NAD concentration with dose-dependent regimens. The secondary objectives were to assess the safety and tolerability of NMN supplementation, next to the evaluation of clinical efficacy by measuring physical performance (six-minute walking test), blood biological age (Aging.Ai 3.0 calculator), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and subjective general health assessment [36-Item Short Form Survey Instrument (SF-36)]. Statistical analysis was performed using the Per Protocol analysis with significant level set at p = 0.05. All 80 participants completed the trial without trial protocol violation. Blood NAD concentrations were statistically significantly increased among all NMN-treated groups at day 30 and day 60 when compared to both placebo and baseline (all p ≤ 0.001). Blood NAD concentrations were highest in the groups taking 600 mg and 900 mg NMN. No safety issues, based on monitoring adverse events (AEs), laboratory and clinical measures, were found, and NMN supplementation was well tolerated. Walking distance increase during the six-minute walking test was statistically significantly higher in the 300 mg, 600 mg, and 900 mg groups compared to placebo at both days 30 and 60 (all p < 0.01), with longest walking distances measured in the 600 mg and 900 mg groups. The blood biological age increased significantly in the placebo group and stayed unchanged in all NMN-treated groups at day 60, which resulted in a significant difference between the treated groups and placebo (all p < 0.05). The HOMA-IR showed no statistically significant differences for all NMN-treated groups as compared to placebo at day 60. The change of SF-36 scores at day 30 and day 60 indicated statistically significantly better health of all three treated groups when compared to the placebo group (p < 0.05), except for the SF-36 score change in the 300 mg group at day 30. NMN supplementation increases blood NAD concentrations and is safe and well tolerated with oral dosing up to 900 mg NMN daily. Clinical efficacy expressed by blood NAD concentration and physical performance reaches highest at a dose of 600 mg daily oral intake. This trial was registered with ClinicalTrials.gov, NCT04823260, and Clinical Trial Registry - India, CTRI/2021/03/032421.
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ItemNo Preview AvailableHeterogeneous aging across multiple organ systems and prediction of chronic disease and mortality(NATURE PORTFOLIO, 2023-05)Biological aging of human organ systems reflects the interplay of age, chronic disease, lifestyle and genetic risk. Using longitudinal brain imaging and physiological phenotypes from the UK Biobank, we establish normative models of biological age for three brain and seven body systems. Here we find that an organ's biological age selectively influences the aging of other organ systems, revealing a multiorgan aging network. We report organ age profiles for 16 chronic diseases, where advanced biological aging extends from the organ of primary disease to multiple systems. Advanced body age associates with several lifestyle and environmental factors, leukocyte telomere lengths and mortality risk, and predicts survival time (area under the curve of 0.77) and premature death (area under the curve of 0.86). Our work reveals the multisystem nature of human aging in health and chronic disease. It may enable early identification of individuals at increased risk of aging-related morbidity and inform new strategies to potentially limit organ-specific aging in such individuals.
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ItemConsensus guidelines for sarcopenia prevention, diagnosis and management in Australia and New Zealand(WILEY, 2023-02)BACKGROUND: Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. METHODS: A four-phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11-point Likert scales with agreement threshold set a priori at >80%, and five multiple-choice questions. Statements with moderate agreement (70%-80%) were revised and re-introduced in Phase 3, and statements with low agreement (<70%) were rejected. In Phase 3, topic experts responded to six revised statements and three additional questions, incorporating results from a parallel Consumer Expert Delphi study. Phase 4 involved finalization of consensus statements. RESULTS: Topic experts from Australia (n = 62, 92.5%) and New Zealand (n = 5, 7.5%) with a mean ± SD age of 45.7 ± 11.8 years participated in Phase 2; 38 (56.7%) were women, 38 (56.7%) were health professionals and 27 (40.3%) were researchers/academics. In Phase 2, 15 of 18 (83.3%) statements on sarcopenia prevention, screening, assessment, management and future research were accepted with strong agreement. The strongest agreement related to encouraging a healthy lifestyle (100%) and offering tailored resistance training to people with sarcopenia (92.5%). Forty-seven experts participated in Phase 3; 5/6 (83.3%) revised statements on prevention, assessment and management were accepted with strong agreement. A majority of experts (87.9%) preferred the revised European Working Group for Sarcopenia in Older Persons (EWGSOP2) definition. Seventeen statements with strong agreement (>80%) were confirmed by the Task Force in Phase 4. CONCLUSIONS: The ANZSSFR Task Force present 17 sarcopenia management and research recommendations for use by health professionals and researchers which includes the recommendation to adopt the EWGSOP2 sarcopenia definition in Australia and New Zealand. This rigorous Delphi process that combined evidence, consumer expert opinion and topic expert consensus can inform similar initiatives in countries/regions lacking consensus on sarcopenia.
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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.