Studiedag Geriatrie, Leuven Bewegen als geneesmiddel. Sarcopenie

Transcription

1 Studiedag Geriatrie, Leuven Bewegen als geneesmiddel Sarcopenie Evelien Gielen MD PhD Dienst Geriatrie & Centrum voor Metabole Botziekten, UZ Leuven

2 Overview Introduction Muscle ageing Evolving concept of sarcopenia Screening & diagnosis of sarcopenia Etiology of sarcopenia Management of sarcopenia Conclusion

3 Evolution of life expectancy at birth

4 Mean life expectancy at birth (years) Life expectancy at birth year 0 22 years

5 Women Men Mean life expectancy at birth (years) Life expectancy at birth y 39.0 y

6 Women Men Mean life expectancy at birth (years) Life expectancy at birth y 77.6 y

7 Women Men Mean healthy life expectancy (years) Mean life expectancy at birth (years) Healthy life expectancy People get older, but have more years with ailments Healthy life expectancy y 77.6 y 65.6 y 65.6 y Het Laatste Nieuws

8 Performance (%) Age-related decline of organ systems Cardiac index Vital capacity GFR Age (years) Adapted from: Shock et al. Canad Med Ass J 1967; 96:

9 Overview Introduction Muscle ageing Evolving concept of sarcopenia Screening & diagnosis of sarcopenia Etiology of sarcopenia Management of sarcopenia Conclusion

10 Age-related loss of muscle mass Peak muscle mass : years Peak muscle mass : years 35-40% loss between age 20 and 80 years Kim et al. J Bone Metab 2013; 20: 1-10; Proctor et al. J Nutr 1998; 128: 351S-355S

11 Age-related loss of muscle mass man, 25 years man, 75 years Rosenberg et al. J Nutr 1997; Baumgartner et al. Am J Epidemiol 1998

12 Age-related loss of muscle mass Calf muscle cross-sectional area Upper vs. lower body muscle mass Lauretani et al. J Appl Physiol 2003; 95: ; Janssen et al. J Appl Physiol 2000; 89: 81-88

13 Age-related loss of muscle mass No decline with age is more dramatic or potentially more significant than the decline in lean body mass. In fact, there may be no single feature of agerelated decline more functionally significant than the decline in lean body mass. Why have we not given it more attention? I suggested that if this phenomenon were to be taken seriously, we had to give it a name. I proposed that the name for this phenomenon should be derived from the Greek. σάρξ (flesh) - πενία (poverty, lack) Rosenberg. Am J Clin Nutr 1989; 50:

14 Overview Introduction Muscle ageing Evolving concept of sarcopenia Screening & diagnosis of sarcopenia Etiology of sarcopenia Management of sarcopenia Conclusion

15 Age-related change of muscle strength Peak muscle strength during 2nd decade 50% Annual loss of muscle strength: % 1.5% 3% Lauretani et al. J Appl Physiol 2003; 95:

16 Age-related change of muscle strength 20% and 10% 65 yr Kneel down Lift a 4,5 kg weight McLeod et al. Biogerontology 2016; 17:

17 Yearly loss (%/year) Loss of muscle mass and strength 0-0,5 men women -1-1,5-2 Muscle mass Muscle strength 1% /y 3% /y -2,5-3 -3,5-4 age-related loss of muscle strength > age-related loss of muscle mass Goodpaster et al. J of Gerontol 2006; 61:

18 A life course model of muscle loss Sayer et al. J Nutr Health Aging 2008; 12:

19 Sarcopenia is Consequences associatedof with frailtypoor outcomes Disabilities in ADL and IADL Poor quality of life Hospitalization Institutionalization Death Falls Cruz-Jentoft et al. Age Ageing 2010; 39: ; Janssen et al. JAGS 2004; 52: 80-5

20 Sarcopenia is Consequences associatedof with frailtypoor outcomes Disabilities in ADL and IADL Poor quality of life Hospitalization Healthcare costs of sarcopenia Direct healthcare cost attributable to sarcopenia 10.8 billion $ 1.5% of total healthcare expenditure in US (2000) 7.7 billion $ Indirect healthcare cost (loss of productivity and autonomy, QoL)? Associated healthcare cost (osteoporosis, obesity, DM type II) Institutionalization Death Falls Cruz-Jentoft et al. Age Ageing 2010; 39: ; Janssen et al. JAGS 2004; 52: 80-5

21 A life course model of muscle loss Range of muscle mass & strength in individuals Sayer et al. J Nutr Health Aging 2008; 12:

22 Overview Introduction Muscle ageing Evolving concept of sarcopenia Screening & diagnosis of sarcopenia Etiology of sarcopenia Management of sarcopenia Conclusion

23 Sarcopenia screening Red flag method Beaudart et al. BMC Geriatrics 2016; 16: 170

24 Sarcopenia screening SARQ-F questionnaire Beaudart et al. BMC Geriatrics 2016; 16: 170

25 Diagnosis of sarcopenia EWGSOP definition Muscle mass Muscle strength Muscle function Physical performance No sarcopenia normal normal normal Pre-sarcopenia normal normal Sarcopenia or Severe sarcopenia and Cruz-Jentoft. Age Ageing 2010

26 a. measurement of muscle mass RASM= Appendicular skeletal muscle mass (alm) by DXA (kg) height ² (m²) > 2 SD below the mean value of a young reference group New Mexico Elder Health Survey (Baumgartner et al) men: RASM 7.26 kg/m² women: RASM 5.45 kg/m² alm= appendicular muscle mass (muscle mass of both arms and legs) RASM= relative appendicular skeletal muscle mass Baumgartner et al. Am J Epidemiol 1998; 147:

27 b. measurement of muscle strength Hand grip strength o hand dynamometer low grip strength Men BMI BMI BMI BMI > BMI Women 3 measurements in dominant hand highest value BMI BMI BMI > Fried et al. J Gerontol A Biol Sci Med Sci 2011

28 c. measurement of physical performance Gait speed o 4 meter course low gait speed < 0.8 m/s usual pace Fried et al. J Gerontol A Biol Sci Med Sci 2011; Cruz-Jentoft et al. Age Ageing 2010

29 Diagnosis of sarcopenia EWGSOP definition Muscle mass Muscle strength Muscle function Physical performance No sarcopenia normal normal normal Pre-sarcopenia normal normal Sarcopenia or Severe sarcopenia and Cruz-Jentoft. Age Ageing 2010

30 Diagnosis of sarcopenia or and Cruz-Jentoft. Age Ageing 2010

31 Prevalence (%) Prevalence of sarcopenia 7,6 7,4 7,2 7,4 7,1 Boston STOP-IT Trial 445 community-dwelling and, aged 65 years 7 6,8 6,6 6,4 6,2 6,6 EWGSOP (1) Acute care Long-term residence 10-20% 14-33% Men Women Both genders Cruz-Jentoft et al. Age Ageing 2010; Cruz-Jentoft et al. Age Ageing 2014; Bischoff-Ferrari et al. Osteoporos Int 2015; 26:

32 Gielen et al. J Cachexia Sarcopenia Muscle 2015; 3; ; ; Bischoff-Ferrari et al. Osteoporos Int 2015; 26: ; Dodds et al. J Cachexia Sarcopenia Muscle 2017; 8: Incidence of sarcopenia increases with age EWGSOP definition Leuven EMAS cohorte (N=433), yr, mean 60 yr mean follow-up: 4.3 yr Sarcopenia (at baseline) Incident sarcopenia (at follow-up) 1.5% 1.6% Boston STOP-It trial (N=445) and, mean age 71 yr 7.1% Newcastle 85+ Study, UK (N=719) and, mean age 85.5 yr mean follow-up: 3 yr 21% 10.9%

33 No consensus definition of sarcopenia Definition Muscle mass Muscle function Low physical performance Low muscle strength EUROPERAN WORKING GROUP ON SARCOPENIA IN OLDER PEOPLE (EWGSOP) (1) low RASM (by DXA or BIA): eg. 2 SD below mean in a young (18-40y) sex-specific reference population (eg. Rosetta): 7.26 kg/m² in men; 5.45 kg/m² in women gait speed < 0.8 m/s (4m walk) (6) or low score SPPPB - grip strength < 30 kg in men < 20 kg in women or - knee extension or INTERNATIONAL WORKING GROUP ON SARCOPENIA (IWGS) (2) low RASM: eg. lowest 20% in healthy elderly (eg. HealthABC) with DXA (7): 7.23 kg/m² in men; 5.67 kg/m² in women gait speed < 1 m/s EUROPEAN SOCIETY FOR CLINICAL NUTRITION AND METABOLISM SPECIAL INTEREST GROUPS (ESPEN-SIG) (3) SOCIETY OF SARCOPENIA, CACHEXIA AND WASTING DISORDERS (SCWD) (4) low total body lean mass: eg. >2 SD below the mean in young adults (18-39y) of same sex in NHANES III (8): SMI 37% in men; 28% in women low RASM: RASM 2 SD below the mean of healthy persons aged 20-30y of the same ethnic group (eg. NHANES IV) 6.81 kg/m² in men; 5.18 kg/m² in women gait speed < 0.8 m/s (4m walk) (6) or reduced performance in any functional test used for CGA gait speed < 1 m/s or 6-minute walk of < 400 m FOUNDATION FOR THE NATIONAL INSTITUTES OF HEALTH SARCOPENIA PROJECT (FNIH) (5) low alm: <19,75 kg (men); < kg (women) low alm BMI : < (men); < (women) grip strength: < 26 kg ; < 16 kg grip strength BMI : <1,00 ; < 0.56 (1) Cruz-Jentoft. Age Ageing 2010; (2) Fielding. J Am Dir Assoc 2011; (3) Muscaritoli. Clin Nutr 2010; (4) Morley. J Am Med Dir Assoc 2011; (5) Studentski. J Gerontol A Biol Sci Med Sci 2014; (6) Guralnik et al. J Gerontol A Biol Sci Med Sci 2005; (7) Newman et al. J Am Geriatr Soc 2003; (8) Janssen et al. Am J Epidemiol 2004

34 Overview Introduction Muscle ageing Evolving concept of sarcopenia Screening & diagnosis of sarcopenia Etiology of sarcopenia Management of sarcopenia Conclusion

35 Muscle protein turnover Muscle protein balance Deutz et al. Clin Nutr 2013; 32: ; Burd et al. Exerc Sport Sci Rev 2013; 41:

36 Etiology of sarcopenia Cruz-Jentoft et al. Curr Opin Clin Nutr Met Care 2010; 13: 1-7

37 Immobility Effect of 10 days of bed rest in older adults Kortebein et al. JAMA 2007;297(16):1772-4

38 Overview Introduction Muscle ageing Evolving concept of sarcopenia Screening & diagnosis of sarcopenia Etiology of sarcopenia Management of sarcopenia Conclusion

39 Management of sarcopenia Muscle protein balance Main anabolic stimuli Physical activity Protein/AA intake Burd et al. Exerc Sport Sci Rev 2013; 41:

40 Anabolic resistance in the elderly Blunted muscle protein synthesis rate in the elderly Muscle protein synthesis (MPS) rate Wall et al. PlosOne 2015; 10 (11): e

41 Anabolic resistance in the elderly Thus, the age-related loss of skeletal muscle mass and strength is essentially due to an imbalance between protein synthesis and degradation rates. Potential strategies to reduce loss of muscle mass/strength (exercise, insulin, leucine) act through an effect on these pathways. Ageing is associated with an impaired ability to activate muscle protein synthesis in respons to insulin, insufficient amounts of proteins/amino-acids or exercise. This is the anabolic resistance of the elderly. However, a sufficient amount of protein or amino acid supplementation and/or a highintensity exercise program is capable of restoring muscle protein synthesis.

42 1. Nutritional intervention Postprandial muscle protein synthesis (MPS) rate is blunted in the elderly Interventions to overcome anabolic resistance with ageing in order to maximize muscle protein synthesis rate a. Protein quantity b. Protein distribution across meals c. Protein quality Muscle protein synthesis rate d. Exercise and timing of ingestion Wall et al. PlosOne 2015; 10 (11): e

43 2. Physical exercise Principles of progressive resistance training in the eldery - Intensity: 60-80% of 1 RM - Individual progression

44 2. Physical exercise Progressive resistance training 8 wks progressive resistance training in 10 elderly > 90y 1 3 times a week 3 series of 8 repetitions 80% of 1 RM o o o 9% quadriceps size 150% muscle strength 50% gait speed 1 Fiatarone et al. JAMA 1990; 263:

45 3. Physical exercise + nutritional intervention 2012 meta-analysis of 22 RCTs Fat-free mass Progressive resistance training + proteins or placebo Leg press strength Cermak et al. Am J Clin Nutr 2012; 96:

46 3. Physical exercise + nutritional intervention Additional intake of proteins/aa in close temporal proximity to exercise + proteins + proteins Physical activity may restore the sensitivity of older muscles to protein or AA intake. In turn, the ingestion of sufficient proteins or AA in close temporal proximity to exercise produces an anabolic stimulus that increases the post-exercise MPS Postprandial MPS rates at rest and after exercise Pennings et al. Am J Clin Nutr 2010; 93:

47 Recommendation of the PTOT-AGE Study Group Recommended dietary protein intake (g/kg body weight/d) g protein per meal, containing about g leucine Protein or amino acid supplementation is recommended in close temporal proximity of exercise g/kg/d Healthy elderly g/kg/d Elderly with an acute or chronic disease 2.0 g/kg/d Elderly with severe illness/injury or marked malnutrition 0.8 g/kg/d Severe kidney disease (< 30 ml/min/1.73m²) In combination with increased protein intake, exercise is recommended at individualized levels that are safe and tolerated Bauer et al. JAMDA 2013; 14:

48 BVGG sarcopenia recommendation Sarcopenia - Prevention & treatment Guideline development project The aim is to translate the actual scientific body of knowledge regarding Sarcopenia into a practice guideline which fits the Belgian context 1. Assessment of muscle mass 2. Assessment of muscle strength 3. Assessment of physical performance 4. Intervention exercise and physical activity 5. Intervention nutrition 6. Intervention pharmacology

49 BVGG sarcopenia recommendation Sarcopenia - Prevention & treatment Guideline development project Intervention exercise and physical activity English systematic reviews reporting on exercise treatment aimed at prevention/ treatment of sarcopenia or sarcopenia outcomes (muscle mass, muscle strength or physical performance) in elderly( 65y) 14 systematic reviews of which 7 performed a meta-analysis

50 BVGG sarcopenia recommendation Sarcopenia - Prevention & treatment Guideline development project Intervention exercise and physical activity A clear and significant effect of resistance training on muscle mass, muscle strength, and physical performance is seen in the evidence. For maximal strength gains a high resistance training (70-80% 1RM) is recommended, but lower intensity (50%) may suffice to induce strength gains. In general we do recommend resistance training to improve muscle strength, muscle mass and physical performance for healthy, pre-sarcopenic or sarcopenic older people in the prevention or treatment of sarcopenia (very high quality of evidence). Data shows clear evidence in favour of multimodal exercise therapy on all three sarcopenic parameters. Multimodal training can encompass a combination of resistance training, walking, aerobic training, balance training and other types. To conclude, we do recommend multimodal exercise therapy for healthy, pre-sarcopenic or sarcopenic older people in the prevention or treatment of sarcopenia (high quality of evidence).

51 BVGG sarcopenia recommendation Sarcopenia - Prevention & treatment Guideline development project Intervention exercise and physical activity Data shows a significant effect of protein supplementation in combination with resistance training on muscle mass and muscle strength (especially leg strength) but no effect on physical performance. Renal function is not negatively affected after supplementation of 20 g protein. In conclusion we do recommend protein supplementation in combination with resistance training for healthy, presarcopenic or sarcopenic older people in the prevention or treatment of sarcopenia (very high quality of evidence). The added effect of nutritional supplementation for resistance training on muscle function appears limited. However, we do recommend VIT D supplementation for resistance training since there is sufficient evidence that vit D may increase the effect of resistance training on muscle strength.

52 Overview Introduction Muscle ageing Evolving concept of sarcopenia Screening & diagnosis of sarcopenia Etiology of sarcopenia Management of sarcopenia Conclusion

53 Conclusion Sarcopenia is the age-related loss of muscle mass and function Sarcopenia leads to adverse outcomes, including disability and death Maintenance of muscle mass and function throughout life, and especially with ageing, is essential to prevent adverse outcomes Etiology of sarcopenia is multifactorial, but essentially results in an imbalance between protein synthesis and degradation Treatment of sarcopenia consists of high-quality interventions that can overcome the anabolic resistance in the elderly

54

55 Studiedag Geriatrie, Leuven Bewegen als geneesmiddel Sarcopenie Evelien Gielen MD PhD Dienst Geriatrie & Centrum voor Metabole Botziekten, UZ Leuven