The LIFE Study. Marco Pahor, MD University of Florida Institute on Aging.

Transcription

1 The LIFE Study Marco Pahor, MD University of Florida Institute on Aging

2 Marco Pahor, MD - Funding disclosure NIH Claude Pepper Older Americans Independence Center P30AG The LIFE Study U01AG The Testosterone Trial (TTrial) U01AG Institute on Aging Clinical Translational Research Building C06RR Clinical Translational Science Award U54RR European Community grant: FRAILOMIC - No:

3 Mobility across species Dickinson et al. Science 2000; 288:5463

4 Aging drosophila and performance Miller et al. Biophys J 2008;95:2391

5 Physical performance declines with age in older rats Carter et al. J Gerontol;2002;57:B193

6 Physical performance and survival in older rats Carter et al. J Gerontol 2002; 57:B193

7 HABC 400 m walk performance and mobility limitation Newman et al. JAMA; 2006;295:2018

8 HABC 400 m walk performance and mortality Newman et al. JAMA; 2006;295:2018

9 Medicare Current Beneficiary Survey Ability to walk ¼ mile, health care cost and hospitalization rates Hardy et al. J Gen Intern Med Online; 2010:Oct 23

10 Predicted life expectancy by age and walking speed in men Studenski et al. JAMA; 2011;305:50

11 Predicted life expectancy by age and walking speed in women Studenski et al. JAMA; 2011;305:50

12 Interventions to maintain mobility ACE inhibitors Albuterol ARBs Aspirin Carnitine CoQ10 Creatine Cytokine inhibitors DHEA Diet high protein Diet low calorie Erythropoietin Estrogens Growth hormone GH secretagogue Myostatin inhibitors NSAIDs Pentoxiphylline Physical activity Resveratrol SARMs Statins Testosterone Thalidomide Vitamin D Vitamin E

13 Major Phase 3 randomized controlled trials with disability outcomes in older persons The Life Study The TTrial ASPREE

14 LIFE Field Centers CA IL PA MA CT LA NC FL N = 1,600 - average FU = 2.7 yrs Range years

15 Outcomes Primary outcome: major mobility Disability defined as incapacity to walk 400 m Secondary outcomes: ADL disability Cognitive function Injurious falls Major mobility disability or death Persistent major mobility disability Cost-effectiveness Tertiary outcomes: cardiopulmonary events, dementia, MCI

16 Cognitive function outcomes Secondary outcome: Digit Symbol Substitution Test (DSST) and the Hopkins Verbal Learning Test (HVLT) Modified Mini-Mental Status Exam (3MS) Modified Rey-Osterrieth Complex Figure Eriksen flanker task N-Back Test measures working memory. Task Switching MCI Dementia

17 70-89 years LIFE Inclusion criteria Sedentary lifestyle (<20 min per week in structured PA, <150 min per week in moderate PA) Able to walk 400 m SPPB score <9 (45% <7) Gives informed consent, lives in the study area and does not plan to move

18 Successful aging intervention Organized health workshops relevant to older adults (e.g., healthful nutrition, how to effectively negotiate the health care system, how to travel safely, etc.) Short instructor-led program (5-10 min) of upper extremity stretching exercises

19 Physical activity intervention Center-based in a group setting Aerobic (walking) Strength (lower extremities) Balance Flexibility stretching Behavioral counseling (group and telephone)

20 Frequency and duration Walking 3 to 6 days per week. (minimum walking bout 10 minutes with goal of 30 minutes per bout) Strength training 3 times per week (10 minutes per session)

21 Intensity: moderate Walking to be performed at 12 to 14 (somewhat hard) on Borg scale Strength training goal will be 15 to 16 (hard) on Borg scale

22 Aerobic University of Florida Wake Forest University

23 Aerobic Stanford University BP check Outdoor walking Taking a break during the walk

24 Resistance

25 Score LIFE-Pilot - SPPB score Physical activity Successful aging mo P<0.001 mo Means estimated from repeated measures ANCOVA adjusted for gender, field center and baseline values Pahor et al J Gerontol 2006;61:1157

26 LIFE-Pilot 400 m walk speed 1 m/sec Physical activity Successful aging 0 6 mo 12 P<0.001 mo Means estimated from repeated measures ANCOVA adjusted for gender, field center and baseline values J Gerontol Biol Sci Med Sci 2006;61:1157

27 LIFE-Pilot - Cumulative hazard mobility disability Number at risk SA 211 PA Cumulative endpoints SA 0 PA Pahor et al. J Gerontol Biol Sci Med Sci 2006;61:

28 LIFE-P Minutes of moderate physical activity Min/week Interventions After end of Interventions Successful aging Physical Activity 0 Baseline 6 mo 12 mo 36 mo Rejeski et al. J Gerontol 2009

29 LIFE-Pilot Physical activity and IL-6 Nicklas et al. JAGS; 2008;56:2045

30 LIFE-Pilot Muscle study Fat accumulation within skeletal muscle is associated with muscle weakness and the loss of function in older adults The effects of physical activity on fat within muscle in older adults are not clear CT scan of the thigh Subcutaneous adipose Goodpaster et al. J Appl Physiol 2008; 105:1498

31 SubQ Area change (cm 2 ) Muscle Area change (cm 2 ) Muscle size N=20 N=22 Successful Aging Physical Activity Subcutaneous adipose tissue Successful Aging Physical Activity LIFE-Pilot Muscle study N=20 N=22 IMAT Area change (cm 2 ) Muscle Specific Torque change (N m/cm 2 ) Intermuscular adipose tissue N=20 P<0.05 N=22 Successful Aging Physical Activity 0 Muscle quality N=20 N=22 P<0.05 Successful Aging Physical Activity

32 Sample Collection/Processing 1635 Participants recruited at 8 sites across the country. Timepoints for blood samples (serum, EDTAplasma, Citrated-plasma, Heparin-plasma) Baseline 6 months [4 of the 8 sites or 800 participants] 12 months 24 months Timepoints for urine samples Baseline 12-month 24-month Timepoints for DNA samples 12-month only

33 Timeline Feb 2010 Nov 2011 Dec 2011 Summer 2012 Dec 2013 Summer 2014 Start randomization n=1600 goal reached n=1635 randomization complete Release of baseline data Follow-up complete Release of follow-up data

34 Next steps for The LIFE Study LIFE Extension Study: Planning the extension of LIFE follow-up and interventions for an additional 5 years to assess the long-term efficacy of physical activity on MCI/Dementia, cardiovascular events, injurious falls and other relevant health outcomes