United Kingdom

Background: Sarcopenia refers to the progressive loss of skeletal muscle mass and function, generally associated with ageing (1). There is growing evidence that sarcopenia is more common in people with cognitive impairment (2). Dementia is the term applied to the clinical syndrome of progressive cognitive decline, negatively impacting on daily function (3). A diagnosis of dementia relies on history taking, examination, and limited investigations, including neuroimaging. A challenging aspect of dementia assessment is that disease severity (assessed on neuropathological features) is not always well correlated with clinical severity (4). Physical frailty may also influence the clinical severity, whereby frailer people are more likely to have a clinical diagnosis of dementia with the same burden of neuropathology as more robust individuals (5). Sarcopenia, representing the physical component of frailty, may provide a clinical tool with which to risk stratify. In terms of sarcopenia evaluation and assessment of skeletal muscle mass and quality, Magnetic Resonance Imaging (MRI) and Computer Tomography (CT) are considered to be gold standards, and Dual-energy X-ray and Bioelectrical impedance analysis are commonly used instruments. However, the clinical evaluation of sarcopenia remains challenging, and a variety of novel tools are being investigated for validity, convenience, and cost-efficiency. Included amongst these are the evaluation of a number of different muscles on CT or MRI, including, recently, the temporalis muscle, as visualised on routine imaging of the brain, as a surrogate marker of sarcopenia evaluation (2). For example, Leitner et al. demonstrated that TMT was associated with Skeletal Muscle Index, suggesting that TMT was reflective of generalised sarcopenia in patients with newly diagnosed brain metastases (6). However, there are currently no studies focussing on patients with memory complaints. Methods: The study cohort comprised of 111 patients attending the memory clinic in 2014. The inclusion criteria were as follows: (a) available coronal MRI of the brain of adequate quality for morphometric assessment, and (b) Frailty Index (FI) data available. FI measures frailty as a ratio between health deficits present in the individual, and the total number of health deficits measured, which is constructed following the guidelines by Rockwood et al (7). Frailty was defined as FI ≥ 0.25, as previously published (7). TMT was analysed on coronal, T1-weighted MR images. The orbital roof and Sylvian fissure were utilised as anatomical landmarks. Measurements were taken perpendicular to the long axis of the muscle. TMT was measured bilaterally, and the average was calculated, resulting in one mean TMT per patient. Shapiro-Wilk test was utilised to assess for normality of distribution of muscle thickness across the cohort. Spearmen correlation test was used to investigate the relationship between TMT and FI. Mann-Whitney U test was utilized to compare distribution of TMT between frail and non-frail patients. Results: Assessment by Shapiro-Wilk test (p = 0.002) suggested a low probability of normal distribution of TMT measures. Spearman correlation test was thus used, and a significant negative correlation of modest magnitude was demonstrated between average TMT and frailty as assessed using FI (rho = -0.24, p = 0.01). Mann-Whitney U test revealed significant difference (Z = -3.341, p = 0.001) in the distribution pattern of average TMT between non-frail (median = 5.7mm, interquartile range = 4.8-6.8) and frail (4.5mm, IQR =4.0-5.6). Together, this supports the hypothesis that increased TMT is associated with decreased frailty in this cohort, and may act as a radiological biomarker of sarcopenia. This is in agreement with previously published studies in other patient groups. This is the first study to examine the use of TMT measurement on coronal MRI in patients with memory complaints; since this is a routine investigation in this cohort, the measurement of TMT may, in future, represent a convenient and fast method by which sarcopenia and frailty can be assessed objectively. Future studies might explore the relationship between TMT and long-term clinical outcomes. Conclusions: The findings of this study support the published literature, and suggest that temporalis muscle thickness, as measured on MRI, may act as a radiological biomarker of sarcopenia in a memory clinic cohort.

ISTRC 2021 - International Sarcopenia Translational Research Conference

Identifying Incidental Biomarkers of Sarcopenia from Routine Imaging in a Memory Clinic Cohort

dementia

frailty

sarcopenia

Welcome to the inaugural International Sarcopenia Translational Research Conference.  “Where Worlds Meet” – the event brings together a broad range of researchers and practitioners in a truly interdisciplinary forum, covering discovery science through to clinical practice.

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Access to this event requires a registration. Please email Eleanor Lockhart at sarcconf@ncl.ac.uk if you have any questions regarding your registration. 

poster

Background: Resistance exercise (RE) is increasingly acknowledged as a primary countermeasure to age related chronic disease and represents an effective strategy for counteracting age-associated declines in muscle strength and physical performance. However, as training induced adaptation is primarily driven by the physiological stress imposed (i.e. the internal training response), eliciting a consistent and standardised training dose is necessary to maximise the potential of RE. Method: Thirty community-dwelling - older adults (71.7 ± 3.6 years; 12 female) naïve to RE, performed 6 weeks of twice weekly, machine-based progressive RE involving a combination of upper- and lower-body exercises (leg press, leg curl, chest press, upright row). RE programming - Participants performed 2-3 sets of 8-10 repetitions for each exercise per session with intensity set at 70% of estimated 1RM in session 1. Load was increased when participants completed the prescribed number of repetitions in the final set while maintaining proper form in two consecutive workouts. Quantification of training response - Internal training response was quantified using ratings of perceived exertion (RPE). Following each RE session, participants provided an overall rating of perceived exertion (sRPE) and differential ratings of perceived exertion for upper-body muscle exertion (sRPE-U) and lower-body muscle exertion (sRPE-L) using the CR100 scale3 . External load was quantified as relative volume load (no. of sets x no. of reps x %1RM). Data were analysed using mixed linear models. Results: Twenty-nine participants completed the intervention with an overall attendance of 97%. Conclusions: RE induced a substantial internal training response. There was no systematic change, but large interindividual variability in response, across the duration of the intervention. These metrics should be validated against objective measures of RE response such as improved muscle function.

Quantifying the internal training response to resistance exercise in older adults: findings from the Milk Intervention Muscle AgeiNg (MIlkMAN) pilot study

Background: Patients with single, large-scale mitochondrial DNA (mtDNA) deletions often present with mitochondrial myopathy for which no treatment is available. Exercise intervention induces beneficial effects in mitochondrial myopathy; however, we do not yet understand the mechanism for this. Aim of the project: This study investigates biochemical, genetic and molecular changes triggered by resistant exercise training to identify exercise modulators on a molecular level in mitochondrial myopathy patients. Material and methods: Pre- and post-exercise vastus lateralis biopsies were taken from a cohort of single, large-scale mtDNA deletion patients (n = 5) after 16 weeks of supervised high-intensity resistant exercise training. Biopsies were assessed for changes in oxidative phosphorylation, mtDNA deletion level, fibre type and size, and differentially expressed (DE) genes (Figure 1). Conclusions: Resistance exercise training was safe and effective for our cohort of single, large-scale mtDNA patients. After exercise: • mitochondrial mass increase correlates with aerobic capability, • complex IV OXPHOS defect ameliorates in all patients, • fibre type I undergo hypertrophy mechanism in 4 patients, • there is differential gene expression. Future investigations of DE genes on SKM tissue with IMC will allow us to characterize their function on a protein level and to highlight potential exercise modulator(s) in mitochondrial myopathy patients.

The effects of resistant exercise training in mitochondrial myopathy patients

Background: Sarcopenia • low muscle quality and quantity • can potentially be represented with psoas muscle area (PMA) Lower PMA associated with adverse outcomes in multiple surgical populations Lower PMA in EVAR population – more conflicting results. Study question: • What are the associations between PMA and mortality in patient’s older than 65 year old with asymptomatic infrarenal AAA undergoing EVAR? • What are the associations between PMA and length of stay, complications, discharge destination and readmissions within 30 days? Methods: Retrospective observational study in single centre tertiary metropolitan hospital Inclusion criteria: Asymptomatic infrarenal AAA from 1/1/13-31/12/17, >65yo Exclusion criteria: Connective tissue disease, mycotic or inflammatory AAA, emergency / non elective cases Primary outcome: Survival from day of operation (in days) Secondary outcomes: 30-day readmissions related to EVAR, Discharge destination (home, residential care, rehabilitation), Complications post surgery (including delirium, infection, post operative bleeding, DVT/PE), Length of stay (days). Results: 122 patients had an EVAR for infrarenal AAA 5 patients excluded as symptomatic 18 patients did not have PMA data (could not find imaging) – no significant differences found between the 2 groups 97 patients in total assessed Characteristics of patients in final analysis as per Table 1. Association found between 5-year mortality and the lowest tertile of PMA, strengthened by adjusting for age, sex and BMI (Figure 1, Table 2) Length of stay appears to be associated with PMA – unlikely clinically significant No significant associations between PMA and complications, discharge destination and readmissions within 30 days – minimal data in other studies to compare to.

Lower Psoas Muscle Area (PMA) is associated with increased mortality after endovascular aneurysm repair in older adults

Background: There is a paucity of cross-sectional research on muscle morphology, function, and functional capability in all age-bands of healthy adults. Therefore, age-related differences in indices of skeletal muscle health across the adult lifespan is unknown. Aim: To evaluate indices of muscle morphology, function and functional capability in a sample of healthy adults aged 18-70yrs. Methods: Study design: Cross sectional study included 274 healthy adults completed the study (mean ± SD: age = 41.9yrs ± 16.1; height = 169.3cm ± 10.2; weight = 72.4kg ± 15.2). Measurements: B mode Ultrasonography and Tensiomyography were used to measure muscle thickness, pennation angle, fascicle length, tissue composition and contractile properties in the vastus lateralis. Measurements of grip strength (handheld dynamometry) and functional capability (1-minute chair rise test) were also undertaken for each participant. Physical activity levels of each participant were recorded (self reported) via the International Physical Activity Questionnaire (short form) to categorise participants physical activity levels as high, moderate or low. Data analysis: Descriptive statistics, correlations, one-way ANOVAs, and multiple regressions were performed (SPSS v25). Results: Descriptive statistics: Age-related characteristics (mean ± standard deviation) per age band are displayed in table 1. Generally indices of skeletal muscle health were lower in the 60-70yr age band compared to the younger age bands. ANOVA and post hoc analysis: Differences in muscle morphology, function and functional capability between the 18-29 age band and the 50-59 and 60- 70 age bands. Physical activity: The mean total MET-min/week (across 7 days) was smaller for the 50-59yr adults (2660.7) compared to the younger groups (18- 29 = 4420.5; 30-39 = 2884.1 and 40-49 = 3232.5). Summary and conclusion: Younger adults (18-29 years) had larger measurements of muscle morphology, strength and functional capability compared to the older adults (60-70 years). Assuming linearity, after 50 years, the difference between decades is equivalent to -0.9% per decade for muscle thickness and strength and -0.5% per decade for muscle architecture. This led to a subsequent difference in functional capability of -1.0% per decade after 50 years of age. Physical activity likely acts to abate detrimental differences in indices of muscle health and maintain functional capacity for activities of daily living. A longitudinal study is required in a sample of healthy female and male adults aged 18-70 years of age to understand the true decline in indices of muscle health due to age.

Age-related characteristics of skeletal muscle health across 18-70 years

Introduction: One in three older adults fall yearly with 30-50% of falls resulting in injury. Falls are estimated to cost £2.3bn yearly in the UK. With an ageing population there is a growing need to be able to identify fallers in order to target fall prevention strategies. Methods: This was an observational cohort study of 4,239 participants (60-90 years) from Wave 6 and 7 of the English Longitudinal Study of Ageing. Low muscle strength (dynapenia) and obesity were defined using criteria below at Wave 6. Selfreported data on falls and fall-related injuries (2-year followup) were collected (Wave 7). Multiple logistic regression analyses were performed adjusting for age, sex and previous fall history. AUC was calculated from logistic models. Conclusion: Abdominal obesity and dynapenia appear to confer a greater risk of falls than either component alone. However, individual discrimination was low. The current challenge remains to find a way to operationalise a functionally relevant definition of dynapenic obesity at an individual level.

Dynapenic Abdominal Obesity as a risk factor for falls and fall-related injuries

Background: Weak grip strength is associated with a range of adverse health outcomes such as disability and mortality1 and an accelerated decline in grip strength confers an even greater health risk2 . Two important areas to consider are long-term conditions (LTCs), which can be used to identify individuals at increased risk of sarcopenia using routine health records, and lifestyle factors, which are potentially modifiable and targets for intervention. Methods: Participants We used data from UK Biobank participants who had grip strength measured at baseline (2006-10) and a subsequent study visit around nine years later. Ethical approval for UK Biobank was obtained from the North West Multi-Centre Research Ethics Committee. At baseline, participants’ LTCs were self-reported and categorised against a hierarchy. The number of LTC categories present was categorised as 0, 1, 2 and 3+ (with 2+ categories classed as multimorbidity). Lifestyle factors (body mass index (BMI), smoking, diet and physical activity) were assessed. Change in grip strength was grouped into four patterns: decline, stable low, stable high or reference (no change or increase)3 . Statistical analysis The sample was restricted to participants with complete data on LTCs, lifestyle factors and patterns of grip strength change. We used multinomial logistic regression to assess associations between exposures (categories of LTCs, multimorbidity and lifestyle factors) and outcome (pattern of grip strength change). Results: A total of 44,315 (51.1% female) participants at ages 40-70 were included in the final sample. The median time between visits was 9.2 (7.6, 10.3) years. In terms of patterns of grip strength change, 6.2% had stable low strength, 6.9% had stable high strength, 15.5% experienced a decline in strength and the remainder (71.4%) were in the reference pattern. Most categories of LTCs had significant independent associations with grip strength change (results not shown). There were graded associations between the degree of multimorbidity and pattern of grip strength change, independent of lifestyle factors. For example, those with three or more categories of LTCs were at increased risk of decline in grip strength, a marked increase in stable low grip strength and were less likely to experience stable high grip strength. All lifestyle factors had significant associations except frequent consumption of processed meat. Low physical activity was associated with adverse patterns of grip strength, while raised BMI had divergent associations (both the decline and stable high patterns of grip strength change). Conclusion: Individuals living with multimorbidity and those with lifestyle risk factors are at increased risk of low muscle strength and loss of strength over time. Our findings suggest potential target groups in mid-life for assessment of grip strength, leading to established interventions such as resistance exercise training and the identification of participants for future research studies.

Long-term conditions, multimorbidity, lifestyle factors and change in grip strength over 9 years of follow-up: findings from 44,315 UK Biobank participants

Methods: This report included Biobank participants recruited between 2006-2010 with COVID-19 test data. Cindex was used to examine predictive discrimination of individual Fried’s frailty components (slowness, weakness, low physical activity, exhaustion, weight loss) and overall status for two COVID-19 outcomes: 1) Mild disease: a positive COVID-19 test from a community setting without evidence of severe disease 2) Severe disease: a positive in-hospital COVID-19 test or COVID-19 as a primary cause of death defined as severe COVID-19. Results: • Out of 358,433 included in the main analysis, 9,679 patients were classified as having mild COVID-19 and 2,964 were classified as having severe COVID-19. • The prevalence of physical frailty was highest in the severe COVID-19 group (8.1%) compared to mild COVID-19 group (3.2%) and with no COVID-19 diagnosis (2.9%). • For severe COVID-19 outcomes, selfreported walking pace provided the greatest risk discrimination compared to other individual frailty indicators, or overall frailty status. Results for mild COVID-19 were similar, however C-index improvement were lower. Summary: A simple self-reported measure of walking pace provides the greatest predictive discrimination for severe COVID-19 outcomes compared to other frailty indicators or overall frailty status.

Physical frailty components and risk prediction of COVID-19 outcomes: UK Biobank analysis


Background and aim: • Muscle weakness is a key criterion for sarcopenia. A condition which is highly prevalent and likely to increase with time as populations age, with profound implications for individuals, their families and society. • Research suggests lower childhood socioeconomic position (SEP) contributes to muscle weakness in later life… • but there is little evidence in younger adults closer to peak muscle strength from more recently born cohorts. • We aimed to examine the relationships between indicators of SEP in childhood and adulthood and grip strength at age 46-years. Methods: The 1970 British Cohort Study (BCS70) is comprised of males and females born in England, Scotland, and Wales during a single week in 1970. A total of 3,113 men and 3,132 women from the BCS70 with data on paternal occupational class and parental education level at age 5 and own occupational class, education level, grip strength and covariates including height, body mass index and occupational activity at age 46, were included in analyses. Interactions between sex and each SEP indicator were formally assessed, and models sex-stratified if evidence of interaction was found. Linear regression models were used to test associations of childhood and adulthood SEP with maximum grip strength. Conclusion & next step: • Women: lower SEP in both childhood and adulthood was associated with weaker grip strength suggesting that strategies to reduce women’s exposure to socioeconomic adversity across life are likely to be beneficial for their peak grip strength. • Men: lower SEP in adulthood appears to be associated with stronger grip at age 46-years related to higher levels of occupational activity. As evidence from other studies suggests associations between SEP and grip strength reverse in later life, strategies may be needed to help men of lower SEP maintain this midlife advantage as they age and retire. • Next step: we will complete a full analysis with more covariates and imputed missing data. This includes examining whether associations vary by body size, health status and health behaviours in childhood and adulthood, and whether associations of different indicators of SEP with grip strength are independent of each other.

Associations between socioeconomic position across life and grip strength at age 46 years: findings from the 1970 British Cohort Study

Introduction: Disadvantaged socioeconomic position (SEP) is associated with adverse health outcomes but has not been extensively studied for the muscle disease sarcopenia. This study aimed to estimate the prevalence of probable sarcopenia in community-dwelling older adults overall, and according to SEP. Methods: Participants from Wave 6 of the English Longitudinal Study of Ageing (ELSA) aged 60 years and older, with measured hand grip strength (HGS) or chair rise test performance were included (n= 6,052). SEP was defined by educational attainment. Conclusion: Disadvantaged socioeconomic position was associated with increased likelihood of probable sarcopenia, along with knownfactors such as older age and low physical activity. Our findings highlight the importanceof including socioeconomic disadvantage inresearch, strategies and polices aimed at theprevention of sarcopenia in older populations.

Health and Socioeconomic determinants of Probable Sarcopenia - 
an analysis of the English Longitudinal Study of Ageing

Introduction:
This research explores dietitians’ determinants of
practice in delivering advice on physical activity in older
adults to prevent sarcopenia. Evidence suggests
additional benefits from combined nutrition and exercise
for the prevention of sarcopenia 3,4, however dietitians
are not often considered as providers of advice on
physical activity. Dietitians are in an ideal position to
maximise every opportunity to provide comprehensive,
holistic advice and ultimately reduce the amount of
professionals patients have to engage with 2,5,6,7,8.
Methodology:
Qualitative methodology was chosen to explore indepth attitudes, opinions and perspectives of
participants.
The epistemological approach isinterpretivism, which
believes we understand and interpret the world
through our experiences, including through our social,
cultural, moral, ideological and political understanding.
The ontological position is relativism which believes
that there are multiple socially constructed realities. 
Conclusion:
Physical activity interventions should be included for all
older adults at risk of sarcopenia as an early intervention
for prevention, therefore, dietitians should offer advice on
physical activity as part of the Making Every Contact Count
initiative as a minimum. Role merging and upskilling of
dietitians can improve patient care and optimise services in
line with the NHS Long Term Plan (2019).

Identifying Incidental Biomarkers of Sarcopenia from Routine Imaging in a Memory Clinic Cohort

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Quantifying the internal training response to resistance exercise in older adults: findings from the Milk Intervention Muscle AgeiNg (MIlkMAN) pilot study

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