“Sarcopenie”Dr. Carel Meskers, revalidatiearts

Kehoe et al. Emerg Med J 2015;32:911-915

%

Medical revolution

Life expectancy at 65 years

GENETIC (“BRAND”)

Bad luck

Lifestyle (use, maintenance)

The medical challenge…

640 muscles

contraction = movement

glucose metabolisme

protein storage

Modifyable!

Vesalius

Muscle

640 muscles

contraction = movement

glucose metabolisme

protein storage

Modifyable!

Vesalius

Muscle

Morgan Int J Biochem Cell Bio, 2003

sarx flesh penia deminished

•

•

low skeletal muscle mass

Sarcopenia

21 jr 63 jr

21 jr 63 jr

Sarcopenie is een ziekte

FP7, MYOAGE

Grip strength

Quadriceps strength

Muscle strength

45-90% lean mass

10-40% fat mass

Ling et al., J Nutr 2011; Ling et al., Age 2011

Muscle mass

Te mager?

Sarcopeen?

Te dik- verlies van spiermassa?

Sarcopeen? Sarcopeen?

Beenakker et al., Ageing Res Rev, 2010

Cruz Jentoft et al. 2018

meta-regression lines with 95% confidence

band (adjusted to 50% female)

General population

20 40 60 80 1000

10

20

30

40

50

60

Age (years)

Gri

p s

tren

gth

(k

g)

89 years

HR 3.7, CI 2.5-5.7

HR 2.6, CI 1.6-4.4

Muscle strength and survival

Ling et al., CMAJ 2009

Harimoto., Brit J Surg 2013

196 pt hepatocellular carcinoma undergoing hepatectomy, CT L3, 40% sarcopenic

Hepatocellular carcinoma - survival

15

17

19

21

23

25

27

Mean

han

dg

rip

str

en

gth

[kg

]

Lowest tertile Middle tertile Highest tertile

MMSE 85 years MMSE 89 years

both p for trend < 0.001

Taekema et al. 2011

Muscle strength and cognition

SPIERMASSA (DEXA) GLUCOSE METABOLISME

Bijlsma et al. AGE 2013

4.0

4.5

5.0

**

Ln

In

su

lin

AU

C

Low Moderate High4.0

4.5

5.0

**

Low Moderate High13

14

15

16

17 **

ALM percentage in tertiles(Relative muscle measure)

Glu

co

se A

UC

Low Moderate High13

14

15

16

17

ALM/Height2 in tertiles

(Absolute muscle measure)

NS

A. B.

C. D.

1

(1A) Study design

(1B) Study population

Yeung et al. 2018

Consistent associationsarcopenia and falls

Sarcopenia predicts

detrimental outcome.

Reijnierse et al. 2015, Gerontology; Bijlsma et al. 2012, Age

Used definitions

Reijnierse et al. 2015, Gerontology; Bijlsma et al. 2012, Age

Used definitions

‘Concordance’ sarcopenia

Older adults

Prevalence 2% to 34%

Reijnierse et al. 2015, Gerontology

Prevalence of sarcopenia is highly dependent on the applied set of diagnostic

criteria.

Cruz-Jentoft et al., Age Ageing 2010

European consensus EWGSOP I

Cruz Jentoft et al. 2018

EWGSOP II

Sarcopenia predicts

detrimental outcome.

‘Consensus like situation’.

Review Cruz-Jentoft 2014

• > 50 years, community dwelling

• 7 studies (2000-2013)

• Median quality

• Resistance training may improving musclestrength and physical performance

• Time of intervention of at least 3 monthsand probably longer

Cruz Jentoft et al. 2014

Progressive resistance training-recommendations

Per week 150 min. moderate or 60 min. high intensity

Intensity: experienced load 5-6/10 of 7-8/10 Borg

3 or more times a week.

8-10 whole body excercises.

Most important muscle groups of legs, hips, chest, back, belly, shoulders and arms.

8-12 repetitions per muscle group.

2 minutes of rest between excercises.

Montero-Fernandez 2013. Eur. J. Phys Rehab Med.; 49 -1

Progressive resistancetrainingmuscle volume (CSA) and satellite cells

Table 2. The association between malnutrition and standardized measures of physical performance in geriatric outpatients

referred to mobility clinics (n= 286)

Z HGS Z LN CST Z Gait speed Z LN TUG Z SPPB Score Side by side Semi-tandem Tandem

Crude

β (95% CI) -0.27 (-0.58,

0.04)

0.52 (0.18, 0.86) -0.56 (-0.86, -

0.25)

0.37 (0.03,

0.72)

-0.42 (-0.74, -

0.11)

0.66 (0.25,

1.76)

0.67 (0.33,

1.34)

0.97 (0.51,

1.80)

p-value 0.083* 0.003 0.000 0.034 0.008 0.406 0.251 0.913

β x SD -2.42 -5.05 -0.16 5.63 -1.37 -- -- --

Model adjusted for age, sex, and multimorbidity

β (95% CI) -0.24 (-0.54,

0.07)

0.53 (0.19, 0.87) -0.49 (-0.78,

0.20)

0.37 (0.03,

0.70)

-0.40 (-0.70, -

0.10)

0.69 (0.23,

2.02)

0.67

(0.31,1.43)

1.02 (0.51,

2.04)

p-value 0.131 0.003 0.001 0.032 0.009 0.497 0.294 0.957

β x SD -2.15 -5.15 -0.14 5.63 -1.30 -- -- --

*Statistically significant results are presented in bold. SPPB = short physical performance battery; CST = chair stand test; TUG = timed up and go; HGS = handgrip

strength; β = beta; CI = confidence interval.

**All measures of physical performance were standardized and presented as gender specific z-scores.

***Interpretation: The β represents the average difference between participants with the presence of malnutrition on physical performance standard deviations (SD),

compared to outpatients without malnutrition. β coefficients were transformed from units of SD to the physical performance measures’ original units by using the

equation β x SD.

N=286 geriatric outpatients

Ramsey et al. In preparation

Nutritional state & physical performance are associated

Table 2. The association between malnutrition and standardized measures of physical performance in geriatric outpatients

referred to mobility clinics (n= 286)

Z HGS Z LN CST Z Gait speed Z LN TUG Z SPPB Score Side by side Semi-tandem Tandem

Crude

β (95% CI) -0.27 (-0.58,

0.04)

0.52 (0.18, 0.86) -0.56 (-0.86, -

0.25)

0.37 (0.03,

0.72)

-0.42 (-0.74, -

0.11)

0.66 (0.25,

1.76)

0.67 (0.33,

1.34)

0.97 (0.51,

1.80)

p-value 0.083* 0.003 0.000 0.034 0.008 0.406 0.251 0.913

β x SD -2.42 -5.05 -0.16 5.63 -1.37 -- -- --

Model adjusted for age, sex, and multimorbidity

β (95% CI) -0.24 (-0.54,

0.07)

0.53 (0.19, 0.87) -0.49 (-0.78,

0.20)

0.37 (0.03,

0.70)

-0.40 (-0.70, -

0.10)

0.69 (0.23,

2.02)

0.67

(0.31,1.43)

1.02 (0.51,

2.04)

p-value 0.131 0.003 0.001 0.032 0.009 0.497 0.294 0.957

β x SD -2.15 -5.15 -0.14 5.63 -1.30 -- -- --

*Statistically significant results are presented in bold. SPPB = short physical performance battery; CST = chair stand test; TUG = timed up and go; HGS = handgrip

strength; β = beta; CI = confidence interval.

**All measures of physical performance were standardized and presented as gender specific z-scores.

***Interpretation: The β represents the average difference between participants with the presence of malnutrition on physical performance standard deviations (SD),

compared to outpatients without malnutrition. β coefficients were transformed from units of SD to the physical performance measures’ original units by using the

equation β x SD.

N=286 geriatric outpatients

Ramsey et al. In preparation

Nutritional state & physical performance are associatedSNAQ score

Protein intake and loss of musclemass

Houston D K et al. Am J Clin Nutr 2008;87:150-155. Ouderen 70-79 jaar.

0,7 0,7 0,8 0,9 1,1 g/kg/day

40% less

loss of

muscle

Afn

am

e in

spie

rma

ssa (kg

)

44

Paddon-Jones, Curr Opin Clin Nutr Metab Care. 2009, Jan;12(1):86-

90. Review.

Optimal protein synthesis at 25-30 grams protein per meal

Extra protein (during breakfast and lunch) + resistance training

Tieland et al., JAMDA 2012

Fa

t fr

ee

ma

ss

Increase in muscle mass

Resistance training and protein supplementation-effect on fat free mass

Cermak et al. AJCN 2012

Sarcopenia predicts

detrimental outcome.

‘Consensus like situation’.

Targeted intervention,

including the old!

Multidisciplinary diagnosis&

treatment

70 years, hazard ratio for the development of disability after

hospitalisation : 61.8

Gill et al JAMA. 2004 Nov 3;292(17):2115-24.

The Empower study

Inception cohort study

• Elderly aged >70

• Admitted to VU Medial Center

• From April to December 2015

• Minimal inclusion criteria.

Predictive value of muscle mass and handgrip strength at

admission and discharge in hospitalized older adults.

N-3

85

ADMISSION DISCHARGE 3 MONTHS

Muscle mass

Strength

ADL

SPBB

SNAQ

#Falls

6-CIT

Muscle mass

Strength

ADL

SPBB

SNAQ

ADL

# Falls

Mortality

Study design (n=385)

• Muscle strength: handgrip strenght

• Muscle mass: Bio Impedance Analyzer

Ancum et al., 2017, Pierik et al 2017

In elderly hospitalized patients

At admission:

•HGS /muscle mass with physical disability (ADL).

•HGS /muscle mass with # falls

•HGS/ muscle mass with cognition

•HGS/ muscle mass with geriatric risk factors

Ancum et al. Gerontology 2017

Ancum et al. Exp Gerontology 2017

Rehab: literature review

Scheerman et al. submitted

Stimulation of physical performance and

physical activity in older patients during

hospitalization: a systematic review.

Inclusion critera

•Hospitalized older patients with a mean age of 65 years

and older,

•Physical interventions with physical performance or

physical activity as outcome measures

Literature review

Scheerman et al. submitted

Stimulation of physical performance and

physical activity in older patients during

hospitalization: a systematic review.

• Twelve RCT’s

• Large heterogenity in applied interventions, dose and

outcome measures.

• Insufficient report on dose

Literature review

Scheerman et al. submitted

Stimulation of physical performance and

physical activity in older patients during

hospitalization: a systematic review.

• Evidence of positive effect of patient- tailored

interventions on muscle measures and physical

performance

• No evidence of effect of non- patient tailored

intervention

Patient tailored= Physical interventions

adapted to the capabilities of the patient

Verlaan et al. J Frailty Aging 2017

Follow- up (3 months)

Disability thresholdSY

ST

EM

DE

CLIN

E

Age

Hospital admission

?

• LoS

• Phenotype

• Acute/ non acute

• Surgical/ non surgical

• Premorbid state

ADDITIONAL

TRAINING

NORMAL ACTIVE

SEDENTARY

(BED REST) BENEFITS?

BENEFITS?

Schrack e.a. 2014

Act

ivit

eit

`leeftijd

Relationship between dose of moderate-to-vigorous-intensity physical activity (MVPA) and

mortality reduction.

David Hupin et al. Br J Sports Med 2015;49:1262-1267

Copyright © BMJ Publishing Group Ltd & British Association of Sport and Exercise Medicine. All rights reserved.

22% minder sterfte

Act

ivit

eit

12u ‘s nachts 8 uur ‘s ochtends 4 uur ‘s middags 12u ‘s avonds

74 jaar en ouder

60 jaar en jonger

Schrack et al 2014

• Vermoeidheid?

• “Het hoort erbij”

• Gebrek aan activiteiten buiten de deur

• Gewoonte/angst.

• Omgeving?

SPIER BEWEGING/ACTIVITEIT

WIJZELF BEWEGING/ACTIVITEIT OMGEVING

PERSOON OMGEVING

Rantakokko et al. 2013

Aantal barrieresSterfte

• Maak het leuk

• Niet te snel te simpel

• Inpassen

• Aanpassen

Lichamelijk actief?

MACH Submission to the MRFF – January 2017 2

randomized clinical trials with short and long term outcomes (WP2);

3) Understanding: of basic biological mechanisms in humans leading to novel interventions being tested within the trial network (WP3);

4) Implementation: of diagnostic strategies and interventions as usual care in geriatric rehabilitation settings (WP4);

5) Dissemination: encouraging screening, diagnostics and intervention on regional, national and international level to expand access to sarcopenia treatments in collaboration with national and international stakeholders (WP5).

6. Project description

The opportunity In geriatric rehabilitation care there is a lack of evidence regarding the epidemiology and treatment of sarcopenia, particularly the benefits of exercise and nutritional interventions. Furthermore, the lack of understanding of biological mechanisms driving sarcopenia in conjunction with other age-related diseases has hindered the development of novel interventions. Highlighting this gap between science and practice, very few healthcare professionals use diagnostic measures or apply appropriate interventions for sarcopenia in clinical practice. EMPOWER-GR will address these issues.

The solution This proposal contains an observational longitudinal multicentre cohort (WP1) of geriatric rehabilitation patients to characterise the epidemiology of sarcopenia stratified by main admission diagnoses (trauma, stroke, infectious disease and cardiopulmonary). Patients will be recruited over six months and followed-up for six months. In 2015-16, 2300 patients were admitted to the participating health care organizations. With an anticipated inclusion rate of 70%, 805 patients are expected to be enrolled. Sarcopenia will be diagnosed based on the EWGSOP criteria5 and health domains (physical, cognitive, and social) will be tested using standardised protocols.

As physical inactivity and protein malnutrition are implicated to be key modifiable causes of sarcopenia, a multicentre, single blinded, cluster randomized clinical trial (WP2) will be conducted (Figure 1). The trial will enrol 180 orthogeriatric patientsi (including both elective and acute orthopaedics (trauma)) admitted to geriatric rehabilitation6-8. The primary endpoint at three months will be lean mass (kg/m2). Secondary endpoints include living independently, muscle strength, physical performance/activity and quality of life. EMPOWER-GR will also assess cost effectiveness of the intervention based on health care utilisation. Mechanistic endpoints include change in myostatin levels, senescent cell load and markers for muscle quality9-11. The physical exercise training will consist of progressive resistance training12-14 three times a week (60% to 80% of 1RM within three weeks). The institutional program will be continued by a strength enhancing exercise program

i Sample size is based on 1.14 kg (SD 1.4 kg) lean mass difference between intervention and control in a community dwelling population.

Taking a larger heterogeneity of our population, the correction for clusters and a loss of follow up of 25% into account, a sample size of 90 patients per group (one to one ratio) is considered.

Figure 1: Study design of

the EMPOWER-GR RCT

Life trajectories

Life trajectories

Life trajectories

• Care_4_muscles:

o Motor – physical function

o Internal organ- health

• Strength training & nutritional state/proteins

• Risks of life events

• Balanced physical activity & Environmental

challenges