The Challenge of Understanding Sarcopenia, Muscle Strength and Disability

1. The Challenge of Understanding Sarcopenia, Muscle Strength and Disability Jack M. Guralnik, M.D., Ph.D. Department of Epidemiology and Public Health University of Maryland School of Medicine

2. Domains of Functioning • Physical • Cognitive • Psychological • Sensory • Social

3. Disability • Expression of a physical or mental limitation in a social context • The gap between a person’s capabilities and the demands of the environment IOM, 1991

4. Disability Domains • Self-care: ADLs • Independence living in the community: IADLs • Mobility (ambulation) at home and in the community: Mobility disability

5. Activities of Daily Living: ADLs Basic Self-Care Tasks • Eating • Dressing • Bathing • Transferring from bed to chair • Using the toilet

6. Instrumental Activities of Daily Living: IADLS • Preparing meals • Shopping • Housekeeping • Managing money • Taking medications • Using the telephone

7. Prevalence of Difficulty Walking ¼ Mile, NHIS, 1998 Mobility 80.1 80 Ability to move through one’s environment without assistance Efficient and reliable locomotion is a fundamental feature of human functioning, and indeed functioning across virtually all animal species 70.2 57.0 60 45.0 Percent 37.5 40 29.4 20 0 65-74 75-84 85+ 65-74 75-84 85+ Women Men

11. Proportion of Persons with Catastrophic and Progressive Disability Among Those Who Developed Severe Disability 100 80 Catastrophic disability 60 Progressive disability Proportion of the severely disabled 40 20 0 M W M W W M W M 75-79 80-84 85+ 69-74 Age (years) Source: Ferrucci et al. J Gerontol Med Sci 1996;51A:M123-M130.

12. Demographics Disease Disability Behavioral risk factors

13. Restrictions in basic physical and mental actions (ambulate, reach, grasp, climb stairs, speak, see standard print) Demographics Functional Limitations Disease Impairments Disability Behavioral risk factors Dysfunction and structural abnormalities in specific body systems (musculoskeletal, cardiovascular, etc.) Theoretical Model of the Pathway from Disease to Disability: Nagi

14. Mean Grip Strength in Nonsurvivors and Survivors at Baseline and Survivors at Follow-up 27 Years Later Honolulu Heart Program and Honolulu Asia Aging Study Source: Rantanen et al. J Appl Physiol 1998;85:2047

15. Mortality Rates in Groups Based on BMI and Hand Grip Strength Honolulu-Asia Aging Study Source: Rantanen et al. J Gerontol Med Sci 2000;55:M168-73.

16. Proportion of Subjects with Functional Limitations in 1991-93 According to Grip Strength Tertiles 25 Years Earlier (3,218 Initially Healthy 45- to 68-year-old Men, HAAS) Functional Limitations Walking Speed 0.4 m/s Grip Strength Tertiles Highest Middle Unable to Rise from a Chair Lowest 0 5 10 15 20 25 30 Percent Source: Rantanen et al. JAMA 1999;281:558-560.

17. Walking 1/2 mile Walking Up 10 Step Dressing Toileting Proportion of Subjects with Disability in 1991-93 According to Grip Strength Tertiles 25 Years Earlier (3,218 Initially Healthy 45- to 68-year-old Men, Honolulu) Self-reported Difficulty Doing Heavy Household Work Grip Strength Tertiles Highest Middle Lowest 0 5 10 15 20 25 30 Percent Source: Rantanen et al., JAMA 1999;281:558-560.

18. Sarcopenia • The age-related loss in skeletal muscle • Sarx = flesh, penia = poverty • IR Rosenberg. Am J ClinNutr1989;50(suppl):1231-3 • WJ Evans & WW Campbell. J Nutr1993;123:465-8

19. The Sarcopenia Hypothesis • Muscle mass is lost progressively after mid-adulthood • Muscle mass correlates with strength • Low strength is a hallmark of disability • Many disabling conditions are associated with accelerated loss of lean mass

20. Age 79 Age 63 Age-related changes in body composition John Turner – Weight Lifter

21. Mid-Femur CT Images from the BLSA (all women with BMI 30-32) Age=80 Years Age=33 Years Age=55 Years

22. Dual Energy X-ray Absorptiometry (DEXA)

23. Skeletal muscle mass and distribution in 468 men and women aged 18–88 yr IAN JANSSEN, STEVEN B. HEYMSFIELD, ZIMIAN WANG, and ROBERT ROSS Men Women J Appl Physiol 89:81-88, 2000

24. The Effect of Bed Rest on Muscle After 10 days of bed rest, healthy older adults lost… • Over 2 pounds of muscle in the legs (6.3% decline) • More than 15% of lower extremity strength Kortebein et al. JAMA 2007;297:1772-4.

25. Longitudinal Percent Change in Muscle Strength by Decade 25-98 yrs. The Baltimore Longitudinal Study of Aging

26. Annualized declines in leg lean mass (hatched bar) and muscle strength (black bar) in the Health ABC Study. Goodpaster BH et al. The Loss of Skeletal Muscle Strength, Mass, and Quality in Older Adults: The Health, Aging and Body Composition Study.J Gerontol A Biol Sci Med Sci. 2006;61:M1059-M1064.

27. Hazard Ratios for Incident Mobility Limitations by Quartiles of Three Muscle Parameters: Health ABC - WOMEN Adjusted for: age, race, site, height, total fat mass, education, alcohol, smoking status physical activity, prevalent disease, self-rated health, depression, cognition and other parameters. Visser et al, J Gerontol A Biol Sci Med Sci. 2005 Mar;60(3):324-33

28. Muscle Mass and Muscle Strength are Not Equivalent • Interventions that increase lean mass don’t necessarily increase strength (e.g. GH). • Strength increases seen with resistance training precede and are far in excess of measurable changes in muscle mass. • Voluntary weight loss leads to losses in skeletal mass but not changes in strength. • Therefore, muscle mass alone is not adequate for characterizing or diagnosing sarcopenia.

29. New Composite Definitions European Working Group on Sarcopenia in Older People1 Low Muscle Mass and Low Muscle Strength or Low Physical Performance ESPEN’s Cachexia-Anorexia & Nutrition in Geriatrics SIGs2 % muscle mass ≥ 2 sd below young adults matched on sex and ethnicity, and Low gait speed (e.g. < 0.8 m/s over 4 meters) • Cruz-Jentoft AJ et al. Age and Ageing 2010;39:412-423 • Muscaritoli M et al Clinical Nutrition 2010;29:154-159

30. “See, the problem with doing things to prolong your life is that all the extra years come at the end, when you’re old.”