FRAILTY, SARCOPENIA & PHYSICAL FUNCTION

Dr Victoria Keevil

Consultant in Geriatric Medicine

Addenbrooke’s Hospital

Aims

• Background

• Concepts of frailty and sarcopenia

• Inactivity, exercise and ageing

BACKGROUND

Population Ageing

Office for National Statistics, UK

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

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…………

FRAILTY & SARCOPENIA

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)

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

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

Frailty, Disability & Co-morbidity

Co-morbidity

Disability

Frailty

Fried et al., J Gerontol A Biol Sci Med Sci, 2001

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

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

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

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

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

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

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

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

Physical Capability Measures

Grip strength, Smedley dynamometer

4m usual walking speed

Chair rises time, x5

Ability to hold a tandem stand for 10seconds

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

Physical Capability Measures and Mortality

Cooper R, Kuh D, Hardy R. BMJ 2010

Short Physical Performance Battery Predicts Future Disability

Guralnik et al., NEJM 1995

What is the relevance of sarcopenia & frailty?

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)

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

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

INACTIVITY & EXERCISE

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’

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)

Sedentariness- TV Viewing time

Wijndaele et al., 2011 IJE; Keevil et al., 2015 MSSE

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)

Is a kilo of lean mass a lot to lose?

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

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

• blunted protein synthesis • Increased proteolysis

• These effects were reversed with rehabilitation, especially in the older subjects.

Results

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)

Sarcopenia and exercise

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

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

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

AcknowledgementsI would like to thank the sponsors listed below.

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

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