Susan Murphy ScD, OTR 1,2,4 Neil Alexander MD 1,3,4

1. Self-reported Fatigue: Relationships with Physical Function and Oxygen Uptake in Leg Osteoarthritis and Type 2 Diabetes Susan Murphy ScD, OTR1,2,4 Neil Alexander MD1,3,4 Mobility Research Center (MRC)1; Department of Physical Medicine and Rehabilitation, University of Michigan2 ; Geriatrics Center and Division of Geriatric Medicine3 University of Michigan Hospitals; VA Ann Arbor Health Care System Geriatric Research Education and Clinical Center (GRECC)4 Acknowledgments: National Institute on Aging; National Center for Medical Rehabilitation Research; American College of Rheumatology Research and Education Foundation; VA Office of Research and Development (Rehab R&D and Medical Research Services)

2. Presentation Part I: Older women with leg osteoarthritis • Daily pain and fatigue, in relation to physical activity • Behavioral intervention to reduce barriers to PA and increase symptom control Part II: Task-specific oxygen uptake and self-reported fatigue in older adults A. As predictors of mobility performance B. In Type 2 diabetes mellitus

3. Symptoms and Physical Activity in Women with OA • 60 women (40 with knee or hip OA, 20 controls) • Mean age 64 + 8 years • 5 day home assessment • Actiwatch-S measured physical activity; recorded symptoms 6 times/day • Pain/fatigue measured on scale of (0- none to 4-extremely severe) • Fatigue defined as “tiredness or weariness”

4. Part I A: Clinical Research Questions • How do pain and fatigue symptoms manifest in daily routines? • How do pain and fatigue symptoms impact physical activity?

5. Pain in Women with OA and Controls (data depicted as means + SE)

6. Fatigue in Women with OA and Controls (data depicted as means + SE)

7. Momentary Within-Day Symptoms by WOMAC Physical Disability

8. Dependent Variable: Physical Activity

9. Summary and Conclusions • For women with mildly painful OA, momentary fatigue may increase more disproportionately through the day than pain, particularly in those with higher disability (more pain) • Increased momentary fatigue is associated with decreased physical activity • Increased pain is associated with increased physical activity • Interventions to increase physical activity and manage symptoms in leg osteoarthritis may need a better emphasis on fatigue Murphy SL et al. Arthritis Rheum 2008

10. Part 1 B: Behavioral Intervention • Current exercise programs for OA limited in their link to activity or environmental context, nor are they designed to reduce individual barriers to PA and improve symptom control • Hypothesis: Compared to those randomized to group exercise and health education, can group exercise plus activity strategy training (AST, an OT approach) more effectively improve pain, fatigue, and physical activity? • Design: • 1 month intervention with 2 and 4 month boosters • 6 month follow-up

11. Baseline Characteristics (Murphy SL et al, Arthritis Rheum, in press)

12. pain fatigue EX+AST EX+ED Pain (time) p<0.005 Fatigue (time x group) p<0.05 Fatigue - Brief Fatigue Inventory, severity subscale; Pain – WOMAC pain subscale Trend for fatigue to decrease in AST and increase in ED

13. (time x group) p<0.05 Activity counts – collected via wrist-worn accelerometry (Actiwatch, MiniMitter-Respironics) Trend for peak activity to increase in AST and decrease in ED

14. Summary and Conclusions • Compared to controls. participants in a group exercise plus activity strategy training designed to reduce individual barriers to PA and improve symptom control had: • Reductions in pain • Reductions in fatigue • Improvements in peak physical activity

15. Part II: Task-specific oxygen uptake and self-reported fatigue in older adults • Global question: How does aerobic function relate to: • mobility performance? • symptoms of exertion and fatigue? • A: Analysis of peak V02 versus submaximal oxygen kinetics in predicting mobility performance. • B: In Type 2 diabetics, analysis of VO2 during peak GXT, submax, and six minute walk (6MW) in predicting perceived exertion (RPE) and fatigue

16. Background and Significance • Age- and disease-associated declines in aerobic capacity (VO2 Max) contribute to functional disability in older adults. • Standard VO2 measures may be limited • Max VO2 (e.g. max treadmill) is difficult to achieve in older adults • Peak VO2 is frequently reported

17. Background and Significance (2) • The aerobic demands of many ADL’s are submaximal • Measures of submaximal (vs maximal or peak) aerobic fitness might: • Be easier and safer to perform, especially for frail older adults • Better predict functional ability

18. Kinetics Of Oxygen Uptake

19. 1000 800 600 Oxygen Uptake (mL/min) 400 200 0 Oxygen Kinetics in Healthy Older Woman Healthy Woman O2 Deficit (63.7 mL) O2 Debt (944.1 mL) Walking Rest Recovery (1.0 mph) 0 180 360 540 720 900 Time (seconds)

20. 1000 800 600 Oxygen Uptake (mL/min) 400 200 0 Oxygen Kinetics in Healthy and Mobility Impaired Older Women Mobility Impaired Woman Healthy Woman O2 Deficit O2 Deficit (873.0 mL) (63.7 mL) 1000 O2 Debt 800 O2 Debt (1734.4 mL) (944.1 mL) 600 Oxygen Uptake (mL/min) 400 200 Walking Walking Rest Recovery (1.0 mph) Rest Recovery (1.0 mph) 0 0 180 360 540 720 900 0 180 360 540 720 900 Time (seconds) Time (seconds)

21. Mean (SEM) Comparisons: Aerobic Unimpaired (n=21) vs Impaired (n=20) *p<0.05 Tcdeficit => Initial oxygen deficit Tcepoc => Excess post-exercise oxygen consumption (Alexander, J Gerontol, 2003)

22. Peak VO2 and Oxygen Kinetics versus Functional Performance: Unimpaired Old ** p<0.01; * p<0.05 (Alexander, J Gerontol, 2003)

23. Peak VO2 and Oxygen Kinetics versus Functional Performance: Impaired Old ** p<0.01; * p<0.05 (Alexander, J Gerontol, 2003)

24. Summary and Conclusions • Older adults with aerobic impairment have: • Slowed submaximal oxygen kinetics • Poor functional mobility performance • Measures of submaximal oxygen kinetics correlate as highly with functional mobility performance as Peak VO2 measures, particularly for impaired old during post-exercise recovery. • Submaximal VO2 kinetics may be more useful than Peak VO2 in estimating the contribution of aerobic function to mobility impairment.

25. Type 2 Diabetics[Enrolled in RCT ex program, age >60, n=56 [27 female]

26. Oxygen Uptake (VO2) Measurements Three tasks: Graduated treadmill (traditional peak) Submaximal treadmill (1 MPH) Six minute walk

27. Self Report Measurements During exercise task: • Rated Perceived Exertion (RPE): How hard you worked • Range 6-20; 11=fairly light; 13=somewhat hard; 15=hard; 17=very hard • Fatigue: How much fatigue you had • 0=No fatigue; 10=Fatigue as bad as could be

30. Self-reported task-specific fatigue is not related to general fatigue

31. Non-peak task-related fatigue may better relate to usual mobility function

32. Task specific self-reported fatigue relates more to VO2 kinetics than peak VO2

33. Summary and Conclusions In this group of relatively functional older adult Type 2 diabetics: • Peak VO2 and post-task fatigue increase with task demand • Self-reported task-specific fatigue is not related to general fatigue • Non-peak task-related fatigue may better relate to usual mobility function • Task specific self-reported fatigue relates more to VO2 kinetics than peak VO2

34. Discussion • Measures acquired during submaximal exercise tests, including 6MW, as opposed to peak GXT, are better indicators of physical function, and likely fatigue. • Future studies should consider: • Whether these relationships hold true for other models of disability and fatigue (such as in non-cardiac disease, high baseline fatigue) • What the underlying physiological link is between subjective fatigue and objective measures of oxygen utilization

35. MRC faculty/collaborators, staff and students/fellows

36. Calculation Of Oxygen Uptake Kinetics k=VO2(SS)/O2 deficit or k= 0.693/t1/2 Area B = VO2(SS)/k VO2 (mL/min) Area A Onset of Work Time (min) Whipp, JAP 30:261-263, 1971

37. Mono-exponential Model of Oxygen Uptake Kinetics VO2=VO2(steady-state)(1-e-(kt)) • VO2 is VO2 above baseline at time t • VO2 is steady state increase in VO2 • k is the rate constant of the reaction with the dimension of t-1