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FRAILTY, SARCOPENIA & PHYSICAL FUNCTION
Dr Victoria Keevil
Consultant in Geriatric Medicine
Addenbrooke’s Hospital
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Aims
• Background
• Concepts of frailty and sarcopenia
• Inactivity, exercise and ageing
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BACKGROUND
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Population Ageing
Office for National Statistics, UK
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Population Ageing• By 2050, 22% of the world’s
population will be >65 years old.
• 2 billion older people.
• In the UK those aged >65 years:• 17% of the total population• 60% of hospital admissions
• The NHS was founded when 48% of the population were not expected to live beyond 65 years old
National Population Projections, 2010-based reference volume: Series PP2Office for National Statistics, UK
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The challenge is to live well into older age……
Who says you can’t have an Arabian nights adventure when you are 99 years old…………
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FRAILTY & SARCOPENIA
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Frailty
• ‘………..a biological syndrome of decreases reserve and resistance to stressors, resulting from cumulative declines across multiple physiologic systems, and causing vulnerability……………’
(Fried et al., J Gerontol A Biol Sci Med Sci, 2001)
• ‘…….a medical syndrome with multiple causes and contributors that is characterised by diminished strength, endurance and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.’
(Morley, J Am Med Dir Assoc, 2013)
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Measurement of Frailty• Frailty Index (Mitnitski, Mogilner , Rockwood, Sci World J, 2001)
• An accummulation of deficits across multiple body systems• Symptom, sign, disability or disease (laboratory biomarker)• Increase with age
• Frailty quantified as the proportion of deficits
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Frailty Index (FI)
Walking ½ mile
Preparing meals
DressingReaching
OutSleepy
Disorder of blood clotting
Hearing Vision Mood
Walking 10steps
Paying bills
Bathing Gripping Emphysema Arrhythmia SBP >140 DBP >80 Bruising
Heavy work
Using phone
ToiletHeart Attack
ArthritisImpaired Speech
Heart failure
CancerMemory
problems
Shopping Eating Lifting Stroke PD Fracture Diabetes AnginaAbnormal
Gait
DISABILITY
CO-MORBIDITY
Armstrong et al., J Gerontol A Biol Sci Med Sci 2014
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Frailty, Disability & Co-morbidity
Co-morbidity
Disability
Frailty
Fried et al., J Gerontol A Biol Sci Med Sci, 2001
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Measurement of Frailty
• Physical Frailty Phenotype (Fried et al., J Gerontol A Biol Sci Med Sci, 2001)
• Exhaustion• Weakness• Slowness• Unintentional weight loss• Low physical activity
• Frailty is quantified as:• Robust: 0• Pre-Frail: 1-2• Frail: >3
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Cycle of Frailty
Chronic MalnutritionDecreased appetite
SarcopeniaDecreased Energy Expenditure
Co-morbidity
Decreased strength Decreased fitness
Reduced walking speed
Disability
Decreased resting metabolic rate
Neuroendocrine dysfunctionSedentary life-style
Weight loss
DependencyAdapted from Fried, J Gerontol A Biol Sci Med Sci, 2001
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Clinical Frailty Scale
• The CFS was an independent predictor of • in-patient mortality
• OR 1.60 (95%CI 1.48, 1.74)
• transfer to a DME ward• OR 1.33 (95%CI 1.24, 1.42)
• LOS >10 days• OR 1.19 (95%CI 1.14, 1.23)
Wallis et al QJM 2015
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Sarcopenia
‘…….there is probably no decline in structure and function more dramatic than the decline in lean body mass or muscle mass over the decades of life.’ (I Rosenberg, J of Nutrition, 1997) Roubenoff, J Geront A Biol Sci Med Sci. 2003
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Cycle of Frailty
Chronic MalnutritionDecreased appetite
SarcopeniaDecreased Energy Expenditure
Co-morbidity
Decreased strength Decreased fitness
Reduced walking speed
Disability
Decreased resting metabolic rate
Neuroendocrine dysfunctionSedentary life-style
Weight loss
DependencyAdapted from Fried, J Gerontol A Biol Sci Med Sci, 2001
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Morley et al., JNHA. 2008
Sarcopenia
Sarcopenia Cachexia Anorexia
Weight loss Mild Severe Moderate
Fat free mass Moderate loss Severe loss Mild loss
Proteolysis Increased Markedly Increased
Normal
Fat mass Normal/ Increased
Marked loss Loss
Anorexia No (mild) Yes Yes
Cytokines Normal/ Mildly Elevated
Markedly elevated
Normal
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EWGSOP Definition
• Sarcopenia is defined as low muscle mass with either low strength and/or low physical performance
A Cruz-Jentoft et al., Age & Ageing 2010
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Frailty & Sarcopenia: Common Ground
Frailty Sarcopenia
Low Physical Function Objectively measured Self-report
• Low Physical Function• Weakness is often the first
manifestation of the PFP (Xue, J
Gerontol A Biol Sci Med Sci 2008)
• Loss of mobility predicts premature mortality in animal models (Fisher, J Am Geriatr Soc 2004)
• Decrease in physical function could reflect need to conserve energy for essential metabolic functions (Schrack, J Am Geriatr Soc 2011)
• Almost all proposed definitions include physical function as a component
Adapted from: Cesari, Frontiers Aging Neuroscience, 2014
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Physical Capability Measures
Grip strength, Smedley dynamometer
4m usual walking speed
Chair rises time, x5
Ability to hold a tandem stand for 10seconds
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48-54 55-59 60-64 65-69 70-74 75-79 80-84 85-9220
40
60
80
100
120
140
160
180Women
9590755025
Age Group
Us
ua
l Wa
lkin
g S
pe
ed
, cm
/s
Range of Usual Walking Speed in the EPIC-Norfolk Study
48-54 55-59 60-64 65-69 70-74 75-79 80-84 85-92
Men
Age Group
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Physical Capability Measures and Mortality
Cooper R, Kuh D, Hardy R. BMJ 2010
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Short Physical Performance Battery Predicts Future Disability
Guralnik et al., NEJM 1995
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What is the relevance of sarcopenia & frailty?
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What is the relevance of sarcopenia & frailty?
• Prevalence in community-based older people (>65 years old):• Frailty
• 2.0-27.0% • Increases with age & female sex
• Sarcopenia• 4.0-17.0%• Increase with age but not always with female sex
• Prevalence in older patient populations
• Frailty: 40% of medical admissions in a Belgium study (Joosten, BMC Geriatrics, 2014)
• Sarcopenia: 26% of medical admission in an Italian study (Rossi, JAMDA, 2014)
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Healthcare Costs• Cost of sarcopenia estimated to be $18.5billion (2000) (Janssen, JAGS,
2004)
• Cost of elective surgical procedures (Robinson et al., Am J Surg, 2011)
• Frail: $76 363 +$48 495 per patient• Non-frail: $27 731 +$15 693 per patient
• Linear association between cost of elective surgery and sarcopenia
Sheetz et al., J Am Coll Surg, 2013
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Are Sarcopenia and Frailty Reversible?
• 754 older people followed-up at 18m intervals
• Frailty defined at each interval by PFP• Robust• Pre-frail• Frail
• Over 54m older adults transitioned between greater and lesser states of frailty• Greater frailty: 43.3%• Lesser frailty: 23.0% Gill, Arch Intern Med, 2006
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INACTIVITY & EXERCISE
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Inactivity or ‘Sedentariness’ • Time awake spent sitting or lying when energy expenditure
is at or just above the basal metabolic rate (≤1.5 METs).
• We spend in excess of 60% of our waking lives sedentary
• ‘Active couch potato’ • Those who achieve current physical activity guidelines (150
mins/week of MVPA) can still be sedentary for 5,730 mins/week.
• Thus, sedentariness has been proposed as an independent risk factor for poor health & there is new research interest in ‘inactive physiology’
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Inactive Physiology and Muscle• Electromyogram recordings
from a leg skeletal muscle during standing, stepping, sitting and rising from a chair reveal that only sitting results in no contractile activity (Hamilton et al., 2007).
• Rats prevented from both exercising and standing or walking have decreased LPL activity in postural muscles resulting in lower plasma HDL cholesterol. (Bey & Hamilton 2003 J Physiol)
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Sedentariness- TV Viewing time
Wijndaele et al., 2011 IJE; Keevil et al., 2015 MSSE
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Hospitalisation- Bed rest
• Bed rest :• 10 days bed rest in older adults (n=12; 67 years; 50% women)
• 1.0 kg loss of lower limb lean tissue mass (Kortebein et al., 2007. JAMA)
• A separate study confirmed 10d bed rest was associated with lower
knee strength, stair climbing power and VO2max (Kortebein et al., 2008. J
Gerontol A Biol Sci Med Sci)
• 28 days bed rest in young men (n=6; 38 years)
• 0.4 kg loss of lower limb lean mass (Paddon-Jones et al., 2003. J Clin
Endocrin & Metab)
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Is a kilo of lean mass a lot to lose?
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Physical Inactivity and Skeletal MuscleYoung vs Old (Tanner et al., 2015. J Physiol)
• Healthy volunteers• 18-35 (n=15; 7 men)• 60-75 (n=9, 2 men)• Both age-groups were similar in terms of BMI, lean mass and
habitual physical activity at baseline
• Study protocol• 4 nights/ 5 day bed rest• 8 week rehabilitation
• 3x/week RET• protein supplementation
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Results
• 5 days of bed rest • reduced leg lean mass in
older but not younger adults
• reduced strength in both groups
• Rehabilitation restored strength and lean mass
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• blunted protein synthesis • Increased proteolysis
• These effects were reversed with rehabilitation, especially in the older subjects.
Results
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Progressive Resistance Exercise Training (PRT)
Peterson, 2010, Aging Res Reviews
Knee extension strength: +12.1kg (10.4, 13.7)
• Several Cochrane reviews have established the benefits of:
• PRT for improving physical function (Liu, 2009)
• Multi-component exercise program reduces rate of falls (Gillespie, 2009)
• Modest evidence some exercise programs improve balance (Howe, 2011)
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Sarcopenia and exercise
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Sarcopenia & Exercise• Exercise (usual RET or multi-faceted interventions
including strength and balance) +/- nutritional interventions:
• Improves muscle strength
• Improves physical performance
• Mixed results with respect to muscle mass
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Frailty and Exercise
• LIFE-P study• 424 community dwelling
older people
• Successful ageing educational programme vs physical activity intervention
Cesari et al., J Geront. Med Sci Series A 2015
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Summary• Frailty (and sarcopenia) are clinical syndromes which are
important to identify in patient populations
• Current interventions which are most evidence based focus on reducing sedentariness and increasing physical activity
• Small differences in activity can make big differences to patients
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AcknowledgementsI would like to thank the sponsors listed below.
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MVPA and Physical Performance
• Amongst those least active (Q1), even 1 minute more MVPA per day was associated with approximately 1cm/s faster UWS (a difference equivalent to 1 year of chronological age).
Keevil et al, under review MSSE
Men Women
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48-54 55-59 60-64 65-69 70-74 75-79 80-84 85-9220
40
60
80
100
120
140
160
180Women
9590755025
Age Group
Us
ua
l Wa
lkin
g S
pe
ed
, cm
/s
Range of Usual Walking Speed in the EPIC-Norfolk Study
48-54 55-59 60-64 65-69 70-74 75-79 80-84 85-92
Men
Age Group
Assumed minimum walking speed at pedestrian road crossings