“Sarcopenie” Dr. Carel Meskers, revalidatiearts
“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