OAIC Overview July 19,2013 PIs: Andrew Goldberg, MD Jay Magaziner, PhD, MS Hyg

1. University of Maryland Older Americans Independence Center OAIC Overview July 19,2013 PIs: Andrew Goldberg, MD Jay Magaziner, PhD, MS Hyg

2. University of Maryland Claude D. Pepper Older Americans Independence Center Mission: Cardiovascular and neuromotor deconditioning are fundamental to the functional impairments and disabilities observed in older people with chronic disease. The goals of the UM-OAIC are to determine the mechanisms and efficacy of motor learning-based exercise rehabilitation programs designed to restore and maintain function and the prevent the functional declines that put older adults with chronic disease at risk for disability.

3. Partnerships Division of Gerontology & Geriatric Medicine VA Geriatric Research, Education, & Clinical Center (GRECC) Kernan Orthopedics and Rehabilitation Hospital VA Geriatrics Service Division of Endocrinology,Diabetes & Nutrition VA Rehabilitation & Development Center of Excellence in Exercise & Robotics for Neurological Disorders (MERCE) Department of Neurology Multiple Sclerosis Center of Excellence Geriatrics & Gerontology, Education & Research Program BaltimoreVA MedicalCenter University of Maryland, Baltimore Mental Health Service MIRECC Center for Research on Aging Loch Raven Community Living Center Nutrition Obesity Research Center University of Maryland Claude D. Pepper Older American Independence Center Regional Medical Education Center (RMEC) Department of Physical Therapy and Rehabilitation Science Chesapeake Health Education Program (CHEP) Department of Epidemiology & Public Health

4. UNIVERSITY OF MARYLAND CLAUDE D. PEPPER OLDER AMERICANS INDEPENDENCE CENTER Principal Investigator: Andrew P. Goldberg, MD External Advisory Board Leadership/Administration Core A. Goldberg, MD, Leader / J. Magaziner, PhD, MS Hyg, Co-Leader Data Safety Monitoring Boards · Full Committee · Subcommittee Administration and Program Management K. Longo, MS A. Sullens, MA Publications Committee Research Cores RC-1: Biostatistics, Informaticsand Translational Research Core Leaders: J. Sorkin, MD, PhD J. Magaziner, PhD, MSHyg RC-2: Applied Physiology and Tissue Mechanisms Core Leaders: A. Ryan, PhD L. Katzel, MD, PhD Pilot/Exploratory Studies Core Core Leaders: M. Rodgers, PhD, PT A. Goldberg, MD Research Career Development Core Core Leaders: A. Goldberg, MD J. Magaziner, PhD, MSHyg RC-3: Mobility Function and Neuromotor Plasticity Core Leaders: R. Macko, MD M. Rogers, PhD, PT

5. Conceptual Model of the UM-OAIC Preventive and Restorative Research in Chronic Diseases of Aging Interdisciplinary Conceptual Model Functional Recovery Aging Clinical Phenotypes Exercise & Neuromotor Learning Rehabilitation Functional Outcomes and Translation into the Community Chronic Disease Improved Quality of Life Pathophysiology& Mechanisms of Functional Impairments Acute Event “Free-Living” Independence Research Working Groups(RC-1) • Community Trials • “Real World” Outcomes • Medical Practice Preventive& Restorative Lifestyle Habits Clinical Evaluation(RC-2) Mechanisms (RC-2,3) Interventions(RC-2,3)

6. RC1: Biostatistics, Informatics & Translational Research Specific Aims: • To provide biostatistical and informatics support to investigators, • Foster the design of motor learning-based exercise rehabilitation interventions • Facilitate the translation of interventions from the laboratory to the clinic and the community • Organize Research Working Groups (RWGs) that will assist OAIC investigators in the design and conduct of research studies

7. RC-1 Research RO1: Community Ambulation Following Hip Fracture (3 clinical sites) • Primary Aim: To determine if a “specific” 16-week multi-modal intervention based on aerobic conditioning, specificity of training, and muscle overload initiated 2-3 months post fracture is more successful in producing community ambulators than a “non-specific” multi-modal control intervention of transcutaneous electrical nerve stimulation, flexibility activities, and active range of motion exercises.

8. R37: Effects of Multi-Modal Exercise Intervention Post Hip Fracture • This is an ancillary study to the Phase III RO1 randomized clinical trial, with specific aims to evaluate mechanisms underlying community ambulation: body composition, bone turnover, hormone regulation, aerobic capacity, balance, gait, inflammation, affect, and cognition.

9. RC 2: Applied Physiology and Tissue Mechanisms Specific Aims: • Facilitate the conduct of musculoskeletal and tissue mechanistic exercise rehabilitation and preventive medical research in aging and disability across the UM-OAIC projects • Perform medical assessments and cardiovascular screening of research volunteers to ensure patient safety and eligibility for research protocols. • Develop and test of novel exercise-based interventions in older volunteers in UM-OAIC research. • Conduct clinical applied training in translational research and the assessment of cardiovascular and physiological outcomes of exercise rehabilitation in aging and laboratory training of standardized core methodologies to facilitate translational research. • Provide study support, mentor and train UM-OAIC researchers in the performance of applied exercise physiology and tissue mechanisms research relevant to exercise–based rehabilitation in older people with chronic disabling diseases

10. Stroke. 2013: In Press • Subjects • Men and women (n=10) • 50-76 years • Lower Body RT • 3x/week • 12 weeks • 1RM Strength • 22% ↑ Leg press • 45% ↑ Leg extension • Insulin Sensitivity • No change in M • M/I ↑31%

11. Stroke. 2011: 42(2):416-420 RT Reduces Muscle Myostatin mRNA Muscle Hypertrophy after RT 16% 40% 14% 49% 27%

12. RC 3: Mobility and Neuromotor Plasticity Specific Aims • Provide expertise and investigator resources to assess the multi-system neuromotor, biomechanical, motor learning and behavioral factors affecting mobility performance.  • Design and conduct of novel motor learning based exercise interventions: • Determine the quantitative measures of whole-body multi-segmental neuromotor control • Understanding the mechanisms of exercise-mediated neuroplasticity of balance, locomotion, and upper limb activities in older people with chronic diseases. • Mentor junior faculty and train UM-OAIC investigators in the mechanistic study of neuromotor control, exercise-mediated neuroplasticity and motor learning.

13. RO1: Intervention to Enhance Lateral Balance Function& Prevent Falls in Aging • Specific Aims • To determine the effects of (a) step training, (b) hip abductor-adductor(AB-AD) muscle strengthening, and (c) a combined step training & muscle strengthening program compared to (d) a standard flexibility & relaxation program (control) on the stepping response characteristics to an external balance perturbation. • To determine the effect of step training, with and without the strengthening intervention, compared to the control group on maximum hip AB-AD joint torque and power. • Secondary aim is to determine the prospective fall frequency of the different intervention groups during monthly follow-up for 1-year post-training.

14. Robotics Training after Stroke Mission and Long-term Objectives: Develop and deploy state-of-the-art modular lower extremity robotic technology to improve walking and balance function and promote durable benefits toward mobility independence in older individuals with stroke and other neurologic diseases.

15. Deficit-adjusted Robotics Training after Stroke • Deficit-adjusted robotic assistance • Terminal stance: push-off for propulsion • Swing: drop foot and safe landing • Level of robotic assistance • Biomechanical models specific to deficit • Capacity to predict optimal robotic support Can a deficit-adjusted approach reduce drop foot and/or increase push off propulsion in chronic hemiparetic stroke?

16. Robotics Training Eliminates Foot Drop in Chronic Stroke community ambulator FREE WALKING TRIALS RETN: 8 deg PRE: 2.5 deg 6 weeks Patient reported discarding use of her assistive ankle brace at home-community at 6-week follow-up and beyond

17. Improvement in Standing Balance: Better Dynamic Inter-limb Weight Transfer -> Reduced Fall Risk DORSAL VIEW OF POSTURAL SWAY 95% confidence ellipse PRE POST Raw time series Anterior-Posterior Center of Pressure (m) Δ Variability of Sway = -50% Medial-Lateral Center of Pressure (m) Medial-Lateral Center of Pressure (m)

18. Selected On-going Trials

19. Recently Funded Trials

20. UM-OAIC Research Career Development Core • Goals: • Provide an enriched, mentor-based research training and educational environment to: • Promote the career development of junior faculty toward independence as investigators in aging-related researchrelated to the UM-OAIC themes. • Train future leaders in academic gerontology and geriatric medicine. • Support the training of trainees and junior faculty pursuing research careers in aging by emphasizing multidisciplinary training to learn novel approaches to improving function and independence in older people.

21. Current RCDC Jr. Scholars • Douglas Savin, PhD, PT (mentors - Drs. Rogers, Wittenberg and Whitall)3rd year RCDC Jr. Scholar “Comparison of Reactive Step Training and Voluntary Task-Oriented Training to Induce Neuromotor Changes for Improving Balance and Preventing Falls”Pilot Funding 07/2012 • Avellino Verceles MD (mentors - Drs. Goldberg, Terrin, and Hasday)3rd year RCDC Jr. Scholar “Development of a Multimodality Strengthening and Mobility Program for Ventilator Dependent Older Patients” Pilot Funding 07/2012 • Michael Dimyan, M.D. (mentors - Drs. Wittenberg, Macko)2nd year RCDC Jr. Scholar “Investigating Brain Network Interactions in Stroke and Aging Using Concurrent Transcranial Magnetic Stimulation and Functional Magnetic Resonance Imaging (TMS-fMRI). Goal is to investigate key brain motor network determinants of movement using concurrent TMS-fMRI”

22. RCDC Jr. Scholars in the Pipeline • Junior faculty at UMB and JHU interested in RCDC Scholar positions: • Laura Buchanan, MD • (Trauma Surgery UM – Acute rehabilitation postabdominal surgery) • Sandra Quezada, MD, MS(Gastroenterologist UM- inflammatory bowel disease) • GautamRamani, MD(Cardiologist UM-rehabilitation in heart failure patients) • Monica Serra, PhD, RD (Exercise physiologist UM- exercise-rehabilitation, metabolism and nutrition in obesity, breast cancer and stroke survivors)

23. Pilot/Exploratory Studies Core (PESC) Goal of the PESC: To provide start-up support for high quality pilot and exploratory research to acquire information needed to select or design future crucial studies of the mechanisms underlying disability, recovery and prevention in older persons and the functional and clinical responses to rehabilitation.

24. 2012 Pilots • Robert Creath, PhD (mentor – Dr. Rogers)“Using Self-triggered, Sensory-enhanced Gaze Shift to Improve Axial Turning Deficits in Persons with Parkinson’s disease.” • Avelino Verceles, MD & Chris Wells, PhD, PT, CCS, ATC(mentor – Dr. Goldberg)“Development of a Rehabilitation Strengthening and Mobility Program for Ventilator Dependent Older Patients.” • Douglas Savin, PhD, PT (mentor – Dr. Rogers)“Comparison of Reactive Step Training & Voluntary Task-Oriented Training to Induce Neuromotor Changes for Improving Balance & Preventing Falls.” • Kelly Westlake, PhD, PT (mentor – Dr. Rogers)“Probing the Neural Basis & Influence of Cognitive Changes on Impaired Balance in Older Adults.”

25. 2013 Pilots • L. Buchanan, MD (mentor – Dr. Magaziner)“Using Rehabilitation and Exercise to Improve Outcome of Older Amercians in the Setting of Emergency Surgical Disease.” • S. Kesmodel, MD & M. Serra PhD (mentor – Dr. Goldberg)“Effects of a Structured Exercise Program on Functional and Metabolic Declines in Postmenopausal Breast Cancer Patients Taking Aromatase Inhibitors.” • D. Loane, PhD (mentor – Dr. Faden)“The Effect of Voluntary Exercise on Microglial Activation Phenotypes and Repair Processes in the Aged Injured Brain.” • N. Steinle, MDH. & Resnick, PhD , MPH (mentor – Dr. Goldberg) “YMCA-Veterans Wellness Program: Pilot Study of a Novel Approach to Weight Loss and Disability Prevention in Older, Overweight Veterans.”

26. Selected Community-Based Programs/Dissemination • Exercise rehabilitation programs for stroke survivors are now based at the Baltimore VA, three senior centers in Howard County, the Loch Raven VA and Kernan Hospital. A collaboration is developing with the Baltimore City Department of Aging senior centers.(Richard Macko, MD) • MyerbergSenior Center is the site of a growing, multi-faceted collaboration with the Center for Research on Aging and a falls prevention research project. (Mark W. Rogers, Ph.D., P.T.) • Weinberg Place is the site of an exercise research and nutrition study, a collaboration between Weinberg Senior Living and School of Nursing investigators. (Barbara Resnick, Ph.D., Kathleen Michael, Ph.D., RN). • The Program in Aging, Trauma, and Emergency Care (PATEC) is collaborating with clinical researchers in the OAIC to develop programs for early rehabilitation of older trauma patients and investigate neural mechanisms underlying brain injury to improve outcomes in older trauma patients. (Jay Magaziner, PhD, MS Hyg)