Publications by authors named "Avan A Sayer"

59 Publications

Prevalence and factors associated with poor performance in the 5-chair stand test: findings from the Cognitive Function and Ageing Study II and proposed Newcastle protocol for use in the assessment of sarcopenia.

J Cachexia Sarcopenia Muscle 2021 Apr 18;12(2):308-318. Epub 2021 Jan 18.

AGE Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK.

Background: Poor performance in the 5-chair stand test (5-CST) indicates reduced lower limb muscle strength. The 5-CST has been recommended for use in the initial assessment of sarcopenia, the accelerated loss of muscle strength and mass. In order to facilitate the use of the 5-CST in sarcopenia assessment, our aims were to (i) describe the prevalence and factors associated with poor performance in the 5-CST, (ii) examine the relationship between the 5-CST and gait speed, and (iii) propose a protocol for using the 5-CST.

Methods: The population-based study Cognitive Function and Ageing Study II recruited people aged 65 years and over from defined geographical localities in Cambridgeshire, Newcastle, and Nottingham. The study collected data for assessment of functional ability during home visits, including the 5-CST and gait speed. We used multinomial logistic regression to assess the associations between factors including the SARC-F questionnaire and the category of 5-CST performance: fast (<12 s), intermediate (12-15 s), slow (>15 s), or unable, with slow/unable classed as poor performance. We reviewed previous studies on the protocol used to carry out the 5-CST.

Results: A total of 7190 participants aged 65+ from the three diverse localities of Cognitive Function and Ageing Study II were included (54.1% female). The proportion of those with poor performance in the 5-CST increased with age, from 34.3% at age 65-69 to 89.7% at age 90+. Factors independently associated with poor performance included positive responses to the SARC-F questionnaire, physical inactivity, depression, impaired cognition, and multimorbidity (all P < 0.005). Most people with poor performance also had slow gait speed (57.8%) or were unable to complete the gait speed test (18.4%). We found variation in the 5-CST protocol used, for example, timing until a participant stood up for the fifth time or until they sat down afterwards.

Conclusions: Poor performance in the 5-CST is increasingly common with age and is associated with a cluster of other factors that characterize risk for poor ageing such as physical inactivity, impaired cognition, and multimorbidity. We recommend a low threshold for performing the 5-CST in clinical settings and provide a protocol for its use.
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http://dx.doi.org/10.1002/jcsm.12660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061374PMC
April 2021

Poor sleep quality and physical performance in older adults.

Sleep Health 2021 Apr 20;7(2):205-211. Epub 2020 Nov 20.

Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.

Objectives: This study aimed to examine the association between sleep quality and physical performance among a group of UK community-dwelling older adults, according to sex.

Methods: Sleep quality was assessed using the Pittsburgh Sleep Quality Index. Physical performance was assessed using a short physical performance battery (SPPB), a timed up-and-go, and a hand-grip strength test.

Results: Of 591 eligible study members, 401 completed the Pittsburgh Sleep Quality Index. In regression analyses, men who reported poor sleep quality were significantly more likely to have a poor SPPB score, even after adjustment for confounding factors (OR = 2.54, 95% CI 1.10-5.89, P= .03). The direction of the relationship was reversed among women, where those who reported poor sleep were less likely to have a low SPPB score (OR = 0.36, 95% CI 0.15-0.85, P = .02). Poor sleep quality was associated with poorer hand-grip strength among women (regression coefficient = -0.34 z score, 95% CI -0.64, -0.04, P = .03), but this relationship was not observed among men (regression coefficient = 0.28 z score, 95% CI -0.01, 0.57, P = .06).

Conclusion: We found evidence of an association between poor sleep quality and poorer physical performance in older adults, though there appear to be important sex differences.
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http://dx.doi.org/10.1016/j.sleh.2020.10.002DOI Listing
April 2021

Prediction of Postoperative Outcomes Following Hip Fracture Surgery: Independent Validation and Recalibration of the Nottingham Hip Fracture Score.

J Am Med Dir Assoc 2021 Mar 4;22(3):663-669.e2. Epub 2020 Sep 4.

Department of Trauma and Orthopaedics, Northumbria Healthcare NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. Electronic address:

Objectives: Independent validation of risk scores after hip fracture is uncommon, particularly for evaluation of outcomes other than death. We aimed to assess the Nottingham Hip Fracture Score (NHFS) for prediction of mortality, physical function, length of stay, and postoperative complications.

Design: Analysis of routinely collected prospective data partly collected by follow-up interviews.

Setting And Participants: Consecutive hip fracture patients were identified from the Northumbria hip fracture database between 2014 and 2018. Patients were excluded if they were not surgically managed or if scores for predictive variables were missing.

Methods: C statistics were calculated to test the discriminant ability of the NHFS, Abbreviated Mental Test Score (AMTS), and American Society of Anesthesiologists (ASA) grade for in-hospital, 30-day, and 120-day mortality; functional independence at discharge, 30 days, and 120 days; length of stay; and postoperative complications.

Results: We analyzed data from 3208 individuals, mean age 82.6 (standard deviation 8.6). 2192 (70.9%) were female. 194 (6.3%) died during the first 30 days, 1686 (54.5%) were discharged to their own home, 211 (6.8%) had no mobility at 120 days, 141 (4.6%) experienced a postoperative complication. The median length of stay was 18 days (interquartile range 8-28). For mortality, C statistics for the NHFS ranged from 0.68 to 0.69, similar to ASA and AMTS. For postoperative mobility, the C statistics for the NHFS ranged from 0.74 to 0.83, similar to AMTS (0.61-0.82) and better than the ASA grade (0.68-0.71). Length of stay was significantly correlated with each score (P < .001 by Jonckheere-Terpstra test); NHFS and AMTS showed inverted U-shaped relationships with length of stay. For postoperative complications, C statistics for NHFS (0.54-0.59) were similar to ASA grade (0.53-0.61) and AMTS (0.50-0.58).

Conclusions And Implications: The NHFS performed consistently well in predicting functional outcomes, moderately in predicting mortality, but less well in predicting length of stay and complications. There remains room for improvement by adding further predictors such as measures of physical performance in future analyses.
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http://dx.doi.org/10.1016/j.jamda.2020.07.013DOI Listing
March 2021

Effect of Angiotensin System Inhibitors on Physical Performance in Older People - A Systematic Review and Meta-Analysis.

J Am Med Dir Assoc 2020 Aug 25. Epub 2020 Aug 25.

AGE Research Group, NIHR Newcastle Biomedical Research Center, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. Electronic address:

Objective: Preclinical and observational data suggest that angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) may be able to improve physical performance in older people via direct and indirect effects on skeletal muscle. We aimed to summarize current evidence from randomised controlled trials in this area.

Design: Systematic review and meta-analysis.

Setting And Participants: Randomized controlled trials enrolling older people, comparing ACEi or ARB to placebo, usual care or another antihypertensive agent, with outcome data on measures of physical performance.

Methods: We searched multiple electronic databases without language restriction between inception and the end of February 2020. Trials were excluded if the mean age of participants was <65 years or treatment was targeting specific diseases known to affect muscle function (for example heart failure). Data were sought on measures of endurance and strength. Standardized mean difference (SMD) treatment effects were calculated using random-effects models with RevMan software.

Results: Eight trials (952 participants) were included. Six trials tested ACEi, 2 trials tested ARBs. The mean age of participants ranged from 66 to 79 years, and the duration of treatment ranged from 2 months to 1 year. Trials recruited healthy older people and people with functional impairment; no trials specifically targeted older people with sarcopenia. Risk of bias for all trials was low to moderate. No significant effect was seen on endurance outcomes [6 trials, SMD 0.04 (95% CI -0.22 to 0.29); P = .77; I = 53%], strength outcomes [6 trials, SMD -0.02 (95% CI -0.18 to 0.14), P = .83, I = 21%] or the short physical performance battery [3 trials, SMD -0.04 (95% CI -0.19 to 0.11), P = .60, I = 0%]. No evidence of publication bias was evident on inspection of funnel plots.

Conclusions And Implications: Existing evidence does not support the use of ACE inhibitors or angiotensin receptor blockers as a single intervention to improve physical performance in older people.
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http://dx.doi.org/10.1016/j.jamda.2020.07.012DOI Listing
August 2020

Immunosenescence profiles are not associated with muscle strength, physical performance and sarcopenia risk in very old adults: The Newcastle 85+ Study.

Mech Ageing Dev 2020 09 28;190:111321. Epub 2020 Jul 28.

AGE Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, United Kingdom. Electronic address:

Decline in immune system function (immunosenescence) has been implicated in several age-related disorders. However, little is known about whether alteration in T-cell senescence, a process underlying immunological ageing, is related to muscle health in very old adults (aged ≥85 years). Utilising data from the Newcastle 85+ Study, we aimed to (a) derive and characterise immunosenescence profiles by clustering 13 baseline immunosenescence-related biomarkers of lymphocyte compartments in 657 participants; (b) explore the association between the profiles and 5-year change in muscle strength (grip strength) and physical performance (Timed Up-and-Go test), and (c) determine whether immunosenescence profiles predict 3-year incident sarcopenia. Two distinct clusters were identified; Cluster 1 ('Senescent-like phenotype', n = 421), and Cluster 2 ('Less senescent-like phenotype', n = 236) in individuals with complete biomarker data. Although Cluster 1 was characterised by T-cell senescence (e.g., higher frequency of CD4 and CD8 senescence-like effector memory cells), and elements of the immune risk profile (lower CD4/CD8 ratio, CMV+), it was not associated with change in muscle function over time, or with prevalent or incident sarcopenia. Future studies will determine whether more in-depth characterisation or change in T-cell phenotypes predict the decline in muscle health in late adulthood.
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http://dx.doi.org/10.1016/j.mad.2020.111321DOI Listing
September 2020

Myoprotective Whole Foods, Muscle Health and Sarcopenia: A Systematic Review of Observational and Intervention Studies in Older Adults.

Nutrients 2020 Jul 28;12(8). Epub 2020 Jul 28.

AGE Research Group, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.

Decline in skeletal muscle strength and mass (sarcopenia) accelerates with age, leading to adverse health outcomes and poor quality of life. Diet plays a crucial role in muscle ageing being an important element of a healthy lifestyle. However, unlike single nutrients, such as dietary protein, or dietary patterns, such as the Mediterranean diet, the relationship between individual whole foods and muscle health has not been systematically evaluated. We aimed to investigate which whole foods (meat, fish, eggs, fruit and vegetables, and non-liquid dairy) may be beneficial (myoprotective) for ageing muscle and sarcopenia in adults aged ≥ 50 years. Nineteen observational and nine intervention studies were identified through systematic searches of the four electronic databases (last search: March 2020). The synthesis of findings showed strong and consistent evidence for a beneficial effect of lean red meat on muscle mass or lean tissue mass in both observational and intervention studies. Higher intake of fruit and vegetables was associated with better muscle function in observational studies, but the evidence from intervention studies was scarce. Non-liquid dairy foods were beneficial for muscle mass in both observational and intervention studies. There was moderate evidence for the role of these foods in muscle strength and sarcopenia, and limited or inconclusive evidence for the benefits of other whole foods (e.g., fish, eggs) for muscle health in older adults. Although current nutritional recommendations are often based on a single nutrient approach, further research about the role of protein-rich and other foods in muscle health will allow for the development of guidelines that are based on whole foods, also highlighting the potential importance of non-protein nutrients within these foods for myoprotection in older adults.
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http://dx.doi.org/10.3390/nu12082257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469021PMC
July 2020

Feasibility and acceptability of a milk and resistance exercise intervention to improve muscle function in community-dwelling older adults (MIlkMAN): Pilot study.

PLoS One 2020 10;15(7):e0235952. Epub 2020 Jul 10.

AGE Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.

Background: Dietary protein supplementation combined with resistance exercise (RE) may counteract declines in muscle strength, mass, and function (sarcopenia), but the role of whole foods rich in protein, such as milk, is less well understood. In the MIlkMAN study, we aimed to examine the feasibility and acceptability of milk+RE as an intervention for muscle function in community-dwelling older adults, and provide exploratory pilot data for future substantive research in population at risk of sarcopenia.

Methods: In a parallel groups design, 30 older adults (71.7±3.6 years; 12 women) were randomised into three groups: WM (whole milk 3.6% fat)+RE, SM (skimmed milk 0.3% fat)+RE, and C (isocaloric carbohydrate drink)+RE. RE was performed twice-weekly over 6 weeks in a community gym, followed by the consumption of 500 ml of milk (~20 g protein) or carbohydrate drink immediately after exercise and a further 500 ml at home within the following 4-5 hours. The feasibility and acceptability of the study was determined by calculating recruitment and attendance rates, compliance with the intervention, rating participants' experiences, and recording adverse health events.

Results: The response rate was 49% (out of 400 invitations sent), and the recruitment rate was 73.2% (30 participants recruited out of 41 screened for eligibility). Twenty-nine participants completed the intervention-an attendance rate of 97.1%; 89.7% rated their experience as 'excellent'/very good'. Compliance with taking the drinks was 97.1% (WM), 98.3% (SM), and 95.0% (C); 93.1% rated their drink intake as 'easy'/'very easy' with no adverse effects. Collection of exploratory pilot data to inform future trials was successful. Mean change in grip strength, 5-chair rises, and gait speed were 0.9±3.4 kg, 1.8±2.2 s, 0.1±0.1 m/s, respectively with no differences between the groups.

Conclusions: This community-based milk+RE intervention was feasible and acceptable to older adults. The study successfully collected pilot data for future substantive research.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235952PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351162PMC
September 2020

Research with older people in a world with COVID-19: identification of current and future priorities, challenges and opportunities.

Age Ageing 2020 10;49(6):901-906

AGE Research Group, Translational and Clinical Research Institute, Biomedical Research Building, Campus for Ageing & Vitality, NIHR Newcastle Biomedical Research Centre, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Older people are disproportionately affected by the COVID-19 pandemic, which has had a profound impact on research as well as clinical service delivery. This commentary identifies key challenges and opportunities in continuing to conduct research with and for older people, both during and after the current pandemic. It shares opinions from responders to an international survey, a range of academic authors and opinions from specialist societies. Priorities in COVID-19 research include its specific presentation in older people, consequences for physical, cognitive and psychological health, treatments and vaccines, rehabilitation, supporting care homes more effectively, the impact of social distancing, lockdown policies and system reconfiguration to provide best health and social care for older people. COVID-19 research needs to be inclusive, particularly involving older people living with frailty, cognitive impairment or multimorbidity, and those living in care homes. Non-COVID-19 related research for older people remains of critical importance and must not be neglected in the rush to study the pandemic. Profound changes are required in the way that we design and deliver research for older people in a world where movement and face-to-face contact are restricted, but we also highlight new opportunities such as the ability to collaborate more widely and to design and deliver research efficiently at scale and speed.
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http://dx.doi.org/10.1093/ageing/afaa149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454250PMC
October 2020

The feasibility of muscle mitochondrial respiratory chain phenotyping across the cognitive spectrum in Parkinson's disease.

Exp Gerontol 2020 09 15;138:110997. Epub 2020 Jun 15.

NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; AGE Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne, United Kingdom. Electronic address:

Introduction: There has been little work on the relationship between sarcopenia, a progressive skeletal muscle disorder, and age-related neurodegenerative diseases such as Parkinson's disease (PD).

Objectives: We aimed to determine: 1) the feasibility of characterizing skeletal muscle across a range of cognitive function in PD; 2) if muscle mitochondrial respiratory chain (MRC) function and content are preserved in older adults with PD.

Methods: Sarcopenia was defined using handgrip strength, chair rise and bioimpedance analysis. MRC function was assessed using phosphorous magnetic resonance spectroscopy (MRS) by estimating τ PCr (s) (phosphocreatine half-time recovery) in the calf muscles following a bout of aerobic exercise. Biopsy of the vastus lateralis muscle was performed, and MRC content assessed by fluorescent immunohistochemistry for porin and components of MRC Complexes I and IV.

Results: Nine participants (78% male; mean age 79.9; PD duration 3.3 years) were recruited. Four had cognitive impairment. Six participants had probable sarcopenia. Eight participants completed MRS and had mean (SD) τ PCr of 37.8 (7.6) seconds, suggesting preserved mitochondrial function. Muscle biopsies were obtained in all and the procedure was well tolerated. Porin Z-score, a proxy for mitochondrial mass, was lower than expected compared to controls (0-89% of fibres with low porin). There was a small amount of Complex I (0.16-4.59%) and Complex IV (0-3.79%) deficiency.

Conclusions: Detailed phenotyping, muscle biopsy and imaging was feasible and acceptable across a spectrum of cognitive function in PD. Sarcopenia was relatively common and may be associated with lower mitochondrial mass and low levels of MRC deficiency.
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http://dx.doi.org/10.1016/j.exger.2020.110997DOI Listing
September 2020

Milk for Skeletal Muscle Health and Sarcopenia in Older Adults: A Narrative Review.

Clin Interv Aging 2020 20;15:695-714. Epub 2020 May 20.

AGE Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.

Skeletal muscle aging manifests as a decline in muscle quantity and quality that accelerates with aging, increasing the risk of sarcopenia. Sarcopenia is characterized by a loss of muscle strength and mass, and contributes to adverse health outcomes in older adults. Intervention studies have shown that sarcopenia may be treated by higher protein intake in combination with resistance exercise (RE). In comparison, less is known about the role of whole protein-containing foods in preventing or treating sarcopenia. Liquid milk contains multiple nutrients and bioactive components that may be beneficial for muscle, including proteins for muscle anabolism that, alone or with RE, may have myoprotective properties. However, there is a lack of evidence about the role of milk and its effects on muscle aging. This narrative review considers evidence from three observational and eight intervention studies that used milk or fortified milk, with or without exercise, as an intervention to promote muscle health and function in older adults (aged 50-99 years). The observational studies showed no association between higher habitual milk consumption and muscle-related outcomes. The results of intervention studies using fortified milk in relation to elements of sarcopenia were also negative, with further inconclusive results from the studies using a combination of (fortified) milk and exercise. Although milk contains nutrients that may be myoprotective, current evidence does not show beneficial effects of milk on muscle health in older adults. This could be due to high habitual protein intakes (>1.0 g/kg BW/d) in study participants, differences in the type of milk (low-fat vs whole) and timing of milk consumption, length of interventions, as well as differences in the sarcopenia status of participants in trials. Adequately powered intervention studies of individuals likely to benefit are needed to test the effectiveness of a whole food approach, including milk, for healthy muscle aging.
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http://dx.doi.org/10.2147/CIA.S245595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247608PMC
November 2020

Study of the Older Adults' Motivators and Barriers Engaging in a Nutrition and Resistance Exercise Intervention for Sarcopenia: An Embedded Qualitative Project in the MIlkMAN Pilot Study.

Gerontol Geriatr Med 2020 Jan-Dec;6:2333721420920398. Epub 2020 May 19.

Newcastle University, Newcastle upon Tyne, UK.

The present study aimed to investigate motivators and barriers to older adults engaging in a nutrition and resistance exercise (RE) intervention for sarcopenia. We conducted a content analysis of structured interviews with 29 community-dwelling older adults (aged 65-80 years) completing the MIlk Intervention Muscle AgeiNg (MIlkMAN) study. Content analysis revealed that self-perceived improved health, knowledge acquisition in nutrition and exercise, social well-being, professional support in a fun environment, and positive reported outcomes were motivators for engagement in the intervention. Peer encouragement, social bonds, and their retention were motivators to continuing engagement after study completion, especially in widowed women. Barriers to maintenance included affordability, environmental factors, and concerns over negative health outcomes. : Nutrition and RE interventions for sarcopenia should focus on knowledge acquisition about their health benefits, being enjoyable, and offering social opportunities that have the potential to last beyond the study duration to promote and maintain positive health behaviors.
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http://dx.doi.org/10.1177/2333721420920398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238441PMC
May 2020

Content of exercise programmes targeting older people with sarcopenia or frailty - findings from a UK survey.

J Frailty Sarcopenia Falls 2020 Mar 1;5(1):17-23. Epub 2020 Mar 1.

AGE Research Group, NIHR Newcastle Biomedical Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University and Newcastle upon Tyne Hospitals NHS Trust, Newcastle, UK.

Objectives: To establish whether existing exercise programmes offered to people with sarcopenia or frailty adhere to the current evidence base.

Methods: We conducted a national survey of practitioners delivering exercise programmes to older people with sarcopenia or frailty in the UK. The link to the online survey was distributed through email lists of professional societies, practice networks and social media. Questions covered target population and programme aims, type, duration and frequency of exercise, progress assessment and outcome measures.

Results: One hundred and thirty-six responses were received. 94% of respondents reported prescribing or delivering exercise programmes to people with sarcopenia or frailty. Most programmes (81/135 [60%]) were primarily designed to prevent or reduce falls. Resistance training was the main focus in only 11/123 (9%), balance training in 61/123 (50%) and functional exercise in 28/123 (23%). Exercise was offered once a week or less by 81/124 (65%) of respondents. Outcome measures suitable for assessing the effect of resistance training programmes were reported by fewer than half of respondents (hand grip: 13/119 [11%]; chair stands: 55/119 [46%]).

Conclusions: Current UK exercise programmes offered to older people with sarcopenia or frailty lack the specificity, frequency or duration of exercise likely to improve outcomes for this patient group.
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http://dx.doi.org/10.22540/JFSF-05-017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155359PMC
March 2020

Current practice in the diagnosis and management of sarcopenia and frailty - results from a UK-wide survey.

J Frailty Sarcopenia Falls 2019 Sep 1;4(3):71-77. Epub 2019 Sep 1.

AGE Research Group, Institute of Neuroscience, Newcastle University, United Kingdom.

Objectives: Despite a rising clinical and research profile, there is limited information about how frailty and sarcopenia are diagnosed and managed in clinical practice. Our objective was to build a picture of current practice by conducting a survey of UK healthcare professionals.

Methods: We surveyed healthcare professionals in NHS organisations, using a series of four questionnaires. These focussed on the diagnosis and management of sarcopenia, and the diagnosis and management of frailty in acute medical units, community settings and surgical units.

Results: Response rates ranged from 49/177 (28%) organisations for the sarcopenia questionnaire to 104/177 (59%) for the surgical unit questionnaire. Less than half of responding organisations identified sarcopenia; few made the diagnosis using a recognised algorithm or offered resistance training. The commonest tools used to identify frailty were the Rockwood Clinical Frailty Scale or presence of a frailty syndrome. Comprehensive Geriatric Assessment was offered by the majority of organisations, but this included exercise therapy in less than half of cases, and medication review in only one-third to two-thirds of cases.

Conclusions: Opportunities exist to improve consistency of diagnosis and delivery of evidence-based interventions for both sarcopenia and frailty.
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http://dx.doi.org/10.22540/JFSF-04-071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155363PMC
September 2019

Developing a composite outcome measure for frailty prevention trials - rationale, derivation and sample size comparison with other candidate measures.

BMC Geriatr 2020 03 25;20(1):113. Epub 2020 Mar 25.

AGE Research Group, NIHR Newcastle Biomedical Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University and Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, NE4 5PL, UK.

Background: Frailty is the loss of ability to withstand a physiological stressor and is associated with multiple adverse outcomes in older people. Trials to prevent or ameliorate frailty are in their infancy. A range of different outcome measures have been proposed, but current measures require either large sample sizes, long follow-up, or do not directly measure the construct of frailty.

Methods: We propose a composite outcome for frailty prevention trials, comprising progression to the frail state, death, or being too unwell to continue in a trial. To determine likely event rates, we used data from the English Longitudinal Study for Ageing, collected 4 years apart. We calculated transition rates between non-frail, prefrail, frail or loss to follow up due to death or illness. We used Markov state transition models to interpolate one- and two-year transition rates and performed sample size calculations for a range of differences in transition rates using simple and composite outcomes.

Results: The frailty category was calculable for 4650 individuals at baseline (2226 non-frail, 1907 prefrail, 517 frail); at follow up, 1282 were non-frail, 1108 were prefrail, 318 were frail and 1936 had dropped out or were unable to complete all tests for frailty. Transition probabilities for those prefrail at baseline, measured at wave 4 were respectively 0.176, 0.286, 0.096 and 0.442 to non-frail, prefrail, frail and dead/dropped out. Interpolated transition probabilities were 0.159, 0.494, 0.113 and 0.234 at two years, and 0.108, 0.688, 0.087 and 0.117 at one year. Required sample sizes for a two-year outcome in a two-arm trial were between 1040 and 7242 for transition from prefrailty to frailty alone, 246 to 1630 for transition to the composite measure, and 76 to 354 using the composite measure with an ordinal logistic regression approach.

Conclusion: Use of a composite outcome for frailty trials offers reduced sample sizes and could ameliorate the effect of high loss to follow up inherent in such trials due to death and illness.
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http://dx.doi.org/10.1186/s12877-020-1463-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098153PMC
March 2020

New horizons in appetite and the anorexia of ageing.

Age Ageing 2020 07;49(4):526-534

Academic Geriatric Medicine, Faculty of Medicine, University of Southampton, Southampton, UK.

Appetite drives essential oral nutritional intake. Its regulation is complex, influenced by physiology, hedonism (the reward of eating) and learning from external cues within a person's society and culture. Appetite loss is common in the older population and not always attributable to medical conditions or treatment. Although the physiological basis of the anorexia of ageing (loss of appetite due to the ageing process) has been established, the effect of ageing on hedonism and external cues, which may be equally important, is less well understood. The anorexia of ageing is associated with reductions in dietary diversity and oral intake, and increased risk of malnutrition, sarcopenia and frailty. Early identification of poor appetite could allow timely intervention before weight loss occurs. There is no standardised tool for assessing appetite in clinical settings at present but the 4-item Simplified Nutritional Appetite Questionnaire (SNAQ) has the potential to be used in this way. This review, designed for clinicians, will discuss the regulation of appetite and the pathogenesis of the anorexia of ageing. It will describe the current evidence for interventions to manage the anorexia of ageing, which is limited, with little benefit reported from individual studies of education, physical activity and medication. There is some positive evidence for flavour enhancement, fortified food and oral nutritional supplements but mainly within single studies. Looking ahead, the aim is to develop multicomponent approaches to the treatment of the anorexia of ageing based on growing understanding of the role of physiological signalling, hedonism and external cues.
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http://dx.doi.org/10.1093/ageing/afaa014DOI Listing
July 2020

Exercise as a treatment for sarcopenia: an umbrella review of systematic review evidence.

Physiotherapy 2020 06 9;107:189-201. Epub 2019 Aug 9.

Institute of Neuroscience | Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK; NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. Electronic address:

Background: Sarcopenia is a progressive and generalised skeletal muscle disorder, and a powerful predictor of adverse health outcomes. Exercise is a widely recommended treatment but consensus about the best approach is lacking.

Objective: To synthesise current systematic review evidence on the effectiveness of exercise in the treatment of sarcopenia to inform clinical practice.

Data Sources: Five electronic databases were searched (15 November 2018): Cochrane Database of Systematic Reviews; MEDLINE without revisions; EMBASE; Scopus; and Web of Science.

Study Selection Or Eligibility Criteria: Systematic reviews and meta-analyses of randomised controlled trials evaluating exercise to treat sarcopenia in adults including sarcopenic outcomes.

Study Appraisal And Synthesis Methods: Review data were extracted and quality assessed (using the AMSTAR 2) by two independent assessors. Due to a lack of eligible reviews, a narrative synthesis of the evidence was performed.

Results: Two reviews were identified which included seven studies with 619 participants. Study exercise interventions included: resistance; mixed and whole body vibration training programmes. Review findings demonstrate limited low quality evidence of positive effects of mixed and resistance training in treating sarcopenia.

Limitations: Limited eligible reviews restricted synthesis and interpretation of findings.

Conclusion And Implications Of Key Findings: There is a lack of high quality research with which to inform the treatment of sarcopenia with exercise. Further research using more precision when selecting sarcopenic populations and outcomes is required in this field. This will enable the identification of effective ways of treating sarcopenia with exercise before evidence-based clinical guidelines can be established.
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http://dx.doi.org/10.1016/j.physio.2019.08.005DOI Listing
June 2020

Sarcopenia, long-term conditions, and multimorbidity: findings from UK Biobank participants.

J Cachexia Sarcopenia Muscle 2020 02 30;11(1):62-68. Epub 2019 Dec 30.

AGE Research Group, NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK.

Background: Sarcopenia, the loss of muscle strength and mass, predicts adverse outcomes and becomes common with age. There is recognition that sarcopenia may occur at younger ages in those with long-term conditions (LTCs) as well as those with multimorbidity (the presence of two or more LTCs), but their relationships have been little explored. Our aims were to describe the prevalence of sarcopenia in UK Biobank, a large sample of men and women aged 40-70 years, and to explore relationships with different categories of LTCs and multimorbidity.

Methods: We used data from 499 046 participants in the baseline of UK Biobank. Our main outcome was probable sarcopenia based on maximum grip strength below sex-specific cut-points. Participants' LTCs were recorded during an interview and categorized against a hierarchy. We used logistic regression to examine the independent associations between each category of LTCs and probable sarcopenia, including adjustment for age, sex, and body mass index. We also examined the association with multimorbidity.

Results: Probable sarcopenia had an overall prevalence of 5.3% and increased with age. The categories with the strongest associations with probable sarcopenia were musculoskeletal/trauma [OR 2.17 (95% CI: 2.11, 2.23)], endocrine/diabetes [OR 1.49 (95% CI: 1.45, 1.55)], and neurological/psychiatric [OR 1.39 (95% CI: 1.34, 1.43)] LTCs. Almost half of the sample (44.5%) had multimorbidity, and they were at nearly twice the odds of probable sarcopenia [OR 1.96 (95% CI: 1.91, 2.02)] compared with those without.

Conclusions: We have shown an overall prevalence of 5.3% of probable sarcopenia at ages 40-70 in UK Biobank. The risk of probable sarcopenia was higher in those with some categories of LTCs, suggesting that these groups may stand to benefit from assessment of sarcopenia, during mid-life as well as old age.
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http://dx.doi.org/10.1002/jcsm.12503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015236PMC
February 2020

Mitochondrial oxidative capacity and NAD biosynthesis are reduced in human sarcopenia across ethnicities.

Nat Commun 2019 12 20;10(1):5808. Epub 2019 Dec 20.

Institute of Developmental Sciences, University of Southampton, Southampton, UK.

The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD levels through perturbed NAD biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.
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http://dx.doi.org/10.1038/s41467-019-13694-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925228PMC
December 2019

Milk and resistance exercise intervention to improve muscle function in community-dwelling older adults at risk of sarcopenia (MIlkMAN): protocol for a pilot study.

BMJ Open 2019 10 8;9(10):e031048. Epub 2019 Oct 8.

NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

Introduction: Sarcopenia is a progressive muscle disorder characterised by decline in skeletal muscle mass, strength and function leading to adverse health outcomes, including falls, frailty, poor quality of life and death. It occurs more commonly in older people and can be accelerated by poor diet and low physical activity. Intervention studies incorporating higher dietary protein intakes or protein supplementation combined with resistance exercise (RE) have been shown to limit muscle function decline. However, less is known about the role of whole foods in reducing the risk of sarcopenia. Milk is a source of high-quality nutrients, which may be beneficial for skeletal muscle. This pilot study examines the feasibility and acceptability of milk consumption with RE to improve muscle function in community-dwelling older adults at risk of sarcopenia.

Methods And Analysis: 30 older adults aged ≥65 years will be randomly allocated to three groups: 'whole milk+RE', 'skimmed milk+RE' or 'control drink+RE'. Assessments will take place in participants' homes, including screening (milk allergies, grip strength, walking speed), baseline and postintervention health and function. All participants will undertake a structured RE intervention twice a week for 6 weeks at a local gym, followed by the consumption of 500 mL of whole or skimmed milk (each ~20 g of protein) or an isocaloric control drink and another 500 mL at home. Participants' views about the study will be assessed using standardised open-ended questions. The primary outcomes include feasibility and acceptability of the intervention with recruitment, retention and intervention response rates. Analyses will include descriptive statistics, exploration of qualitative themes and intervention fidelity.

Ethics And Dissemination: Outputs include pilot data to support funding applications; public involvement events; presentation at conferences and peer-reviewed publication.

Trial Registration Number: ISRCTN13398279; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2019-031048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797244PMC
October 2019

Factors associated with change in self-reported physical activity in the very old: The Newcastle 85+ study.

PLoS One 2019 16;14(7):e0218881. Epub 2019 Jul 16.

AGE Research Group, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.

Background: Higher physical activity (PA) has been linked to better health and functioning. Trajectories of PA and associated factors have been studied in older adults aged ≥65, but less is known about influences on PA change in the very old (aged ≥85).

Objective: To investigate factors associated with self-reported PA and PA change over time in very old adults.

Methods: 845 participants in the Newcastle 85+ Study were followed for health and functioning at 1.5-, 3-, and 5-year follow-up (wave 2 to 4). PA scores (range 0-18) and PA levels (low (PA scores 0-1), medium (2-6) and high (7-18)) were determined using a purpose-designed PA questionnaire. We used linear mixed models (LMM) to investigate factors associated with 5-year change in PA scores.

Results: Overall, men had higher mean PA scores than women (up to 2.27 points). The highest proportion of participants (42-48%) had medium levels of PA across the waves. Although most experienced decline-stability in moderate and increases in high PA levels were also observed. The fully adjusted LMM revealed a curvilinear annual decline in PA scores of 0.52 (0.13) (β (SE), p<0.001), which decelerated by 0.07 (0.02) points (p<0.01) over time. The factors associated with low PA scores at baseline were female gender, higher waist-hip ratio, and no alcohol intake. Better self-rated and cognitive health and having fewer diseases were associated with higher PA scores. None were associated with the rate of change in PA over time.

Conclusion: We observed a curvilinear trend and deceleration in PA scores decline in the very old. Men and those in better health and who drank alcohol were more physically active at baseline. None of the factors were associated with the rate of PA decline. Investigating those who maintain or increase levels of PA may inform interventions for at risk groups with PA decline.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218881PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6634376PMC
February 2020

Sarcopenia.

Lancet 2019 Jun 3;393(10191):2636-2646. Epub 2019 Jun 3.

AGE Research Group, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK; National Institute for Health Research, Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Newcastle University, Newcastle upon Tyne, UK.

Sarcopenia is a progressive and generalised skeletal muscle disorder involving the accelerated loss of muscle mass and function that is associated with increased adverse outcomes including falls, functional decline, frailty, and mortality. It occurs commonly as an age-related process in older people, influenced not only by contemporaneous risk factors, but also by genetic and lifestyle factors operating across the life course. It can also occur in mid-life in association with a range of conditions. Sarcopenia has become the focus of intense research aiming to translate current knowledge about its pathophysiology into improved diagnosis and treatment, with particular interest in the development of biomarkers, nutritional interventions, and drugs to augment the beneficial effects of resistance exercise. Designing effective preventive strategies that people can apply during their lifetime is of primary concern. Diagnosis, treatment, and prevention of sarcopenia is likely to become part of routine clinical practice.
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http://dx.doi.org/10.1016/S0140-6736(19)31138-9DOI Listing
June 2019

Comprehensive geriatric assessment in primary care: a systematic review.

Aging Clin Exp Res 2020 Feb 9;32(2):197-205. Epub 2019 Apr 9.

Academic Geriatric Medicine, Faculty of Medicine, University of Southampton, Southampton, UK.

Background: Comprehensive geriatric assessment (CGA) involves the multidimensional assessment and management of an older person. It is well described in hospital and home-based settings. A novel approach could be to perform CGA within primary healthcare, the initial community located healthcare setting for patients, improving accessibility to a co-located multidisciplinary team.

Aim: To appraise the evidence on CGA implemented within the primary care practice.

Methods: The review followed PRISMA recommendations. Eligible studies reported CGA on persons aged ≥ 65 in a primary care practice. Studies focusing on a single condition were excluded. Searches were run in five databases; reference lists and publications were screened. Two researchers independently screened for eligibility and assessed study quality. All study outcomes were reviewed.

Results: The authors screened 9003 titles, 145 abstracts and 97 full texts. Four studies were included. Limited study bias was observed. Studies were heterogeneous in design and reported outcomes. CGAs were led by a geriatrician (n = 3) or nurse practitioner (n = 1), with varied length and extent of follow-up (12-48 months). Post-intervention hospital admission rates showed mixed results, with improved adherence to medication modifications. No improvement in survival or functional outcomes was observed. Interventions were widely accepted and potentially cost-effective.

Discussion: The four studies demonstrated that CGA was acceptable and provided variable outcome benefit. Further research is needed to identify the most effective strategy for implementing CGA in primary care. Particular questions include identification of patients suitable for CGA within primary care CGA, a consensus list of outcome measures, and the role of different healthcare professionals in delivering CGA.
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http://dx.doi.org/10.1007/s40520-019-01183-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033083PMC
February 2020

Dietary Patterns, Skeletal Muscle Health, and Sarcopenia in Older Adults.

Nutrients 2019 Mar 30;11(4). Epub 2019 Mar 30.

AGE Research Group, Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

In recent decades, the significance of diet and dietary patterns (DPs) for skeletal muscle health has been gaining attention in ageing and nutritional research. Sarcopenia, a muscle disease characterised by low muscle strength, mass, and function is associated with an increased risk of functional decline, frailty, hospitalization, and death. The prevalence of sarcopenia increases with age and leads to high personal, social, and economic costs. Finding adequate nutritional measures to maintain muscle health, preserve function, and independence for the growing population of older adults would have important scientific and societal implications. Two main approaches have been employed to study the role of diet/DPs as a modifiable lifestyle factor in sarcopenia. An a priori or hypothesis-driven approach examines the adherence to pre-defined dietary indices such as the Mediterranean diet (MED) and Healthy Eating Index (HEI)-measures of diet quality-in relation to muscle health outcomes. A posteriori or data-driven approaches have used statistical tools-dimension reduction methods or clustering-to study DP-muscle health relationships. Both approaches recognise the importance of the whole diet and potential cumulative, synergistic, and antagonistic effects of foods and nutrients on ageing muscle. In this review, we have aimed to (i) summarise nutritional epidemiology evidence from four recent systematic reviews with updates from new primary studies about the role of DPs in muscle health, sarcopenia, and its components; (ii) hypothesise about the potential mechanisms of 'myoprotective' diets, with the MED as an example, and (iii) discuss the challenges facing nutritional epidemiology to produce the higher level evidence needed to understand the relationships between whole diets and healthy muscle ageing.
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http://dx.doi.org/10.3390/nu11040745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521630PMC
March 2019

The feasibility of assessing frailty and sarcopenia in hospitalised older people: a comparison of commonly used tools.

BMC Geriatr 2019 02 15;19(1):42. Epub 2019 Feb 15.

Academic Geriatric Medicine, University of Southampton, Southampton, UK.

Background: Frailty and sarcopenia are common amongst hospitalised older people and associated with poor healthcare outcomes. Widely recognised tools for their identification are the Fried Frailty Phenotype, its self-report version the FRAIL Scale, and the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. We studied the feasibility of using these tools in a hospital setting of acute wards for older people.

Methods: Patients aged 70+ years admitted to acute wards at one English hospital were prospectively recruited. The Fried Frailty Phenotype was assessed through measured grip strength, gait speed and questions on unintentional weight loss, exhaustion and physical activity. The 5-item self-reported FRAIL scale questionnaire covering the same domains was completed. Agreement between the two tools was reported using the Cohen kappa statistic. The EWGSOP criteria (gait speed, grip strength and muscle mass) were assessed by additional bedside measurement of muscle mass with bioelectrical impedance.

Results: Two hundred thirty three participants (median age 80 years, 60% men) were recruited. Most (221, 95%) had their grip strength measured: 4 (2%) were unable and data were missing for 8 (3%). Only 70 (30%) completed the gait speed assessment: 153 (66%) were unable with missing data on 10 (4%). 113 (49%) participants had the bioelectrical impedance assessment. Muscle mass measurement was not possible for 84 (36%) participants: 25 patients declined, 21 patients were unavailable, 22 results were technically invalid, and 16 had clinical contra-indications. Data on 36 (15%) were missing. Considering inability to complete grip strength or gait speed assessments as low values, data for the Fried Frailty Phenotype was available for 218 (94%) of participants; frailty was identified in 105 (48%). 230 (99%) patients completed the FRAIL scale; frailty was identified among 77 (34%). There was moderate agreement between the two frailty tools (Kappa value of 0.46, 95%CI: 0.34 to 0.58). Complete data for the EWGOSP criteria were only available for 124 (53%) patients of whom 40 (32%) had sarcopenia.

Conclusion: It was feasible to measure grip strength and complete the FRAIL scale among older inpatients in hospital. Measuring gait speed and muscle mass to identify sarcopenia was challenging in the acute setting.

Trial Registration: ISRCTN registry (ID ISRCTN16391145 ) on 30.12.14.
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http://dx.doi.org/10.1186/s12877-019-1053-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377779PMC
February 2019

Effects of dietary patterns and low protein intake on sarcopenia risk in the very old: The Newcastle 85+ study.

Clin Nutr 2020 01 21;39(1):166-173. Epub 2019 Jan 21.

Newcastle University Institute for Ageing, Newcastle Upon Tyne, United Kingdom; Institute of Health & Society, Newcastle University, Newcastle Upon Tyne, United Kingdom.

Background: Sarcopenia, a progressive age-related loss of skeletal muscle mass and strength, leads to disability, falls, and hospitalisation. Individual variation in sarcopenia onset may be partly explained by lifestyle factors such as physical activity and diet. Healthy dietary patterns (DPs) have been linked to better physical functioning in older adults, but their role in sarcopenia in the very old (aged ≥85) is unknown.

Aims: To investigate the association between DPs and the risk of sarcopenia over 3 years, and to determine whether protein intake influences this relationship in community-dwelling older adults from the Newcastle 85 + Study.

Methods: The analytic sample consisted of 757 participants (61.2% women) who had dietary assessment at baseline. After two-step clustering with 30 food groups to derive DPs, we used logistic regression to determine the risk of prevalent and incident sarcopenia across DPs in all participants, and in those with low (<1 g/kg adjusted body weight/day [g/kg aBW/d]) and good protein intake (≥1 g/kg aBW/d).

Results: We identified three DPs (DP1: 'Low Red Meat', DP2: 'Traditional British' and DP3: 'Low Butter') that varied by unsaturated fat spreads/oils, butter, red meat, gravy and potato consumption. Compared with participants in DP3, those in DP2 had an increased risk of prevalent (OR = 2.42, 95% CI: 1.15-5.09, p = 0.02) but not 3-year incident sarcopenia (OR = 1.67, 0.59-4.67, p = 0.33) adjusted for socio-demographic, anthropometry, health and lifestyle factors. Furthermore, DP2 was associated with an increased risk of prevalent sarcopenia at baseline (OR = 2.14, 1.01-4.53, p = 0.05) and 3-year follow-up (OR = 5.45, 1.81-16.39, p = 0.003) after adjustment for key covariates in participants with good protein intake.

Conclusion: A DP high in foods characteristic of a traditional British diet (butter, red meat, gravy and potato) was associated with an increased risk of sarcopenia even when overall protein intake was good. The results need to be replicated in other cohorts of the very old to understand the role of DPs in sarcopenia onset and management.
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http://dx.doi.org/10.1016/j.clnu.2019.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961212PMC
January 2020

Quadriceps miR-542-3p and -5p are elevated in COPD and reduce function by inhibiting ribosomal and protein synthesis.

J Appl Physiol (1985) 2019 06 24;126(6):1514-1524. Epub 2019 Jan 24.

Molecular Medicine Section, National Heart and Lung Institute, Imperial College, South Kensington Campus, London , United Kingdom.

Reduced physical performance reduces quality of life in patients with chronic obstructive pulmonary disease (COPD). Impaired physical performance is, in part, a consequence of reduced muscle mass and function, which is accompanied by mitochondrial dysfunction. We recently showed that miR-542-3p and miR-542-5p were elevated in a small cohort of COPD patients and more markedly in critical care patients. In mice, these microRNAs (miRNAs) promoted mitochondrial dysfunction suggesting that they would affect physical performance in patients with COPD, but we did not explore the association of these miRNAs with disease severity or physical performance further. We therefore quantified miR-542-3p/5p and mitochondrial rRNA expression in RNA extracted from quadriceps muscle of patients with COPD and determined their association with physical performance. As miR-542-3p inhibits ribosomal protein synthesis its ability to inhibit protein synthesis was also determined in vitro. Both miR-542-3p expression and -5p expression were elevated in patients with COPD (5-fold < 0.001) and the degree of elevation associated with impaired lung function (transfer capacity of the lung for CO in % and forced expiratory volume in 1 s in %) and physical performance (6-min walk distance in %). In COPD patients, the ratio of 12S rRNA to 16S rRNA was suppressed suggesting mitochondrial ribosomal stress and mitochondrial dysfunction and miR-542-3p/5p expression was inversely associated with mitochondrial gene expression and positively associated with p53 activity. miR-542-3p suppressed RPS23 expression and maximal protein synthesis in vitro. Our data show that miR-542-3p and -5p expression is elevated in COPD patients and may suppress physical performance at least in part by inhibiting mitochondrial and cytoplasmic ribosome synthesis and suppressing protein synthesis. miR-542-3p and -5p are elevated in the quadriceps muscle of patients with chronic obstructive pulmonary disease (COPD) in proportion to the severity of their lung disease. These microRNAs inhibit mitochondrial and cytoplasmic protein synthesis suggesting that they contribute to impaired exercise performance in COPD.
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http://dx.doi.org/10.1152/japplphysiol.00882.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551227PMC
June 2019

Assessment and Treatment of the Anorexia of Aging: A Systematic Review.

Nutrients 2019 Jan 11;11(1). Epub 2019 Jan 11.

Academic Geriatric Medicine, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.

(1) Background: Appetite loss in older people, the 'Anorexia of Aging' (AA), is common, associated with under-nutrition, sarcopenia, and frailty and yet receives little attention. This review had two aims: describe interventions for AA and their effectiveness, and identify the methods of appetite assessment. (2) Methods: Study inclusion: participants aged ≥65, intervention for AA, and appetite assessment, any design, and comparator. Exclusion: studies on specific health cohorts. Searches in four databases with hand searching of references and citing works. Two researchers independently assessed eligibility and quality. (3) Results: Authors screened 8729 titles, 46 full texts. Eighteen articles were included describing nine intervention types: education ( = 1), exercise ( = 1), flavor enhancement ( = 2), increased meal variety ( = 1), mealtime assistance ( = 1), fortified food ( = 1), oral nutritional supplement (ONS) ( = 8), amino acids ( = 1), and medication ( = 2). Three studies evaluated combinations: education + exercise, ONS + exercise, and ONS + medication. Five intervention types exhibited favorable effects on appetite but in single datasets or not replicated. Appetite was assessed predominantly by Likert ( = 9), or visual analogue scales ( = 7). (4) Conclusions: A variety of interventions and methods of appetite assessments were used. There was a lack of clarity about whether AA or undernutrition was the intervention target. AA is important for future research but needs standardized assessment so that effectiveness of a range of interventions can be fully explored.
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http://dx.doi.org/10.3390/nu11010144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356473PMC
January 2019

Multimorbidity Predicts Quality of Life but not Motor Severity in Early Parkinson's Disease.

J Parkinsons Dis 2018 ;8(4):511-515

Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.

Recent guidance by the National Institute for Health and Care Excellence (NICE) focuses on the management of people with multimorbidity, including Parkinson's disease (PD). To date there has been little exploration of this in neurodegenerative diseases. This study aimed to explore the associations between multimorbidity, motor severity and quality of life (QoL) in early PD. Regression analyses determined whether multimorbidity was significantly associated with disease severity and QoL. Multimorbidity was a small but significant predictor of QoL in people with incident PD, but not motor severity, suggesting that they may benefit from a tailored multidisciplinary approach to care.
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http://dx.doi.org/10.3233/JPD-181428DOI Listing
October 2019

Can trained volunteers improve the mealtime care of older hospital patients? An implementation study in one English hospital.

BMJ Open 2018 08 5;8(8):e022285. Epub 2018 Aug 5.

Medicine for Older People, University Hospital Southampton NHS FT, Southampton General Hospital, Southampton, UK.

Objective: Multinational studies report undernutrition among 39% older inpatients; importantly, malnutrition risk may further increase while in hospital. Contributory factors include insufficient mealtime assistance from time-pressured hospital staff. A pilot study showed trained volunteers could safely improve mealtime care. This study evaluates the wider implementation of a mealtime assistance programme.

Design: Mixed methods prospective quasi-experimental study.

Setting: Nine wards across Medicine for Older People (MOP), Acute Medical Unit, Orthopaedics and Adult Medicine departments in one English hospital.

Participants: Patients, volunteers, ward staff.

Intervention: Volunteers trained to help patients aged ≥70 years at weekday lunchtime and evening meals.

Main Outcome Measures: The number of volunteers recruited, trained and their activity was recorded. Barriers and enablers to the intervention were explored through interviews and focus groups with patients, ward staff and volunteers. The total cost of the programme was evaluated.

Results: 65 volunteers (52 female) helped at 846 meals (median eight/volunteer, range 2-109). The mix of ages (17-77 years) and employment status enabled lunch and evening mealtimes to be covered. Feeding patients was the most common activity volunteers performed, comprising 56% of volunteer interactions on MOP and 34%-35% in other departments. Patients and nurses universally valued the volunteers, who were skilled at encouraging reluctant eaters. Training was seen as essential by volunteers, patients and staff. The volunteers released potential costs of clinical time equivalent to a saving of £27.04/patient/day of healthcare assistant time or £45.04 of newly qualified nurse time above their training costs during the study.

Conclusions: Patients in all departments had a high level of need for mealtime assistance. Trained volunteers were highly valued by patients and staff. The programme was cost-saving releasing valuable nursing time.

Trial Registration Number: NCT02229019; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2018-022285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078263PMC
August 2018

Subcellular origin of mitochondrial DNA deletions in human skeletal muscle.

Ann Neurol 2018 08 21;84(2):289-301. Epub 2018 Aug 21.

Department of Psychiatry, Division of Behavioral Medicine, Columbia University Medical Center, New York, NY.

Objective: In patients with mitochondrial DNA (mtDNA) maintenance disorders and with aging, mtDNA deletions sporadically form and clonally expand within individual muscle fibers, causing respiratory chain deficiency. This study aimed to identify the sub-cellular origin and potential mechanisms underlying this process.

Methods: Serial skeletal muscle cryosections from patients with multiple mtDNA deletions were subjected to subcellular immunofluorescent, histochemical, and genetic analysis.

Results: We report respiratory chain-deficient perinuclear foci containing mtDNA deletions, which show local elevations of both mitochondrial mass and mtDNA copy number. These subcellular foci of respiratory chain deficiency are associated with a local increase in mitochondrial biogenesis and unfolded protein response signaling pathways. We also find that the commonly reported segmental pattern of mitochondrial deficiency is consistent with the three-dimensional organization of the human skeletal muscle mitochondrial network.

Interpretation: We propose that mtDNA deletions first exceed the biochemical threshold causing biochemical deficiency in focal regions adjacent to the myonuclei, and induce mitochondrial biogenesis before spreading across the muscle fiber. These subcellular resolution data provide new insights into the possible origin of mitochondrial respiratory chain deficiency in mitochondrial myopathy. Ann Neurol 2018;84:289-301.
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http://dx.doi.org/10.1002/ana.25288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141001PMC
August 2018