OAIC OverviewJuly 19,2013

PIs: Andrew Goldberg, MDJay Magaziner, PhD, MS Hyg

University of Maryland Older Americans Independence Center

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.

Partnerships

BaltimoreVA Medical

Center

VA Geriatric Research, Education, & Clinical

Center (GRECC)

VA Geriatrics Service

VA Rehabilitation & Development Center of Excellence in Exercise &

Robotics for Neurological Disorders (MERCE)

Loch Raven Community Living Center

Chesapeake Health Education Program (CHEP)

Center for Research on Aging

Geriatrics & Gerontology,Education & Research Program

Division of Endocrinology,Diabetes & Nutrition

Department of Epidemiology & Public Health

Department of Physical Therapy and Rehabilitation Science

Nutrition Obesity Research Center

Department of Neurology

University of Maryland, Baltimore

Kernan Orthopedics and Rehabilitation Hospital

Division of Gerontology & Geriatric Medicine

Regional Medical Education Center (RMEC)

University of Maryland Claude D. Pepper Older American

Independence Center

Mental Health Service MIRECC

Multiple Sclerosis Center of Excellence

External Advisory Board

UNIVERSITY OF MARYLAND CLAUDE D. PEPPER OLDER AMERICANS INDEPENDENCE CENTER

Principal Investigator: Andrew P. Goldberg, MD

Leadership/Administration CoreA. Goldberg, MD, Leader / J. Magaziner, PhD, MS Hyg, Co-Leader

Research Cores

Research Career Development Core

Core Leaders:A. Goldberg, MDJ. Magaziner, PhD, MSHyg

Pilot/Exploratory Studies Core

Core Leaders:M. Rodgers, PhD, PTA. Goldberg, MD

RC-2: Applied Physiology and Tissue

MechanismsCore Leaders:

A. Ryan, PhDL. Katzel, MD, PhD

RC-1: Biostatistics, Informaticsand Translational Research

Core Leaders:J. Sorkin, MD, PhDJ. Magaziner, PhD, MSHyg

RC-3: Mobility Function and Neuromotor Plasticity

Core Leaders:R. Macko, MDM. Rogers, PhD, PT

Administration and Program ManagementK. Longo, MS A. Sullens, MA

Data Safety Monitoring Boards· Full Committee · Subcommittee

Publications Committee

Conceptual Model of the UM-OAIC

Aging

Acute Event

Chronic Disease

Clinical Phenotypes

Exercise & Neuromotor

Learning Rehabilitation

Functional Outcomes and Translation into the Community

Functional Recovery

Preventive and Restorative Research in Chronic Diseases of Aging Interdisciplinary Conceptual Model

•Community Trials•“Real World” Outcomes•Medical Practice

Research Working Groups

(RC-1)Mechanisms

(RC-2,3)

Preventive& Restorative

Lifestyle Habits

Clinical Evaluation(RC-2)

Improved Quality of Life

Interventions(RC-2,3)

Pathophysiology& Mechanisms of

Functional Impairments

“Free-Living”Independence

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

• 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.

RC-1 ResearchRO1: Community Ambulation Following Hip Fracture

(3 clinical sites)

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.

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

Stroke. 2013: In Press

1RM Strength• 22% ↑ Leg press• 45% ↑ Leg extension

Insulin Sensitivity• No change in M• M/I ↑31%

Subjects• Men and women

(n=10)• 50-76 years

Lower Body RT• 3x/week• 12 weeks

Stroke. 2011: 42(2):416-420

Muscle Volume

500

700

900

1100

1300

1500

1700

1900

2100

Paretic Non-Paretic

Vo

lum

e (c

m3 )

Pre

Post

*

†

Muscle Hypertrophy after RT

Myostatin

0

50

100

150

200

250

Paretic Non-Paretic

Arb

itra

ry U

nit

s (

au

)

Pre

Post

*

*

RT Reduces Muscle Myostatin mRNA

14%

16%40%

49%27%

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.

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.

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.

Deficit-adjusted Robotics Training after Stroke

Can a deficit-adjusted approach reduce drop foot and/or increase push off propulsion in chronic hemiparetic 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

Robotics Training Eliminates Foot Drop in Chronic Stroke

FREE WALKING TRIALS

RETN: 8 deg

PRE: 2.5 deg

Patient reported discarding use of her assistive ankle brace at home-community at 6-week follow-up and beyond

PRE POST RETN0

20

40

60

80

100

47

7682

Gai

t Sp

eed

(cm

/s)

COMMUNITY

AMBULATOR

0 2 4 6 8 10 12 14 16 18 200

3

5

8

10

13

Training visit

Pea

k Sw

ing

Ang

le

(deg

)

6 weeks

Improvement in Standing Balance: Better Dynamic Inter-limb Weight Transfer -> Reduced Fall Risk

Ante

rior-

Post

erio

r Cen

ter o

f Pre

ssur

e (m

)

Medial-Lateral Center of Pressure (m)

Raw time series95% confidence ellipse

PRE

Medial-Lateral Center of Pressure (m)

POST

DORSAL VIEW OF POSTURAL SWAY

Δ Variability of Sway = -50%

Selected On-going Trials

PI Trial Population

J. Magaziner, PhD, MS Hyg/ R. Craik, PhD, PT Community Ambulation Following Hip Fracture (RC 1, 2, 3)

 Hip Fracture

M. Stuart, PhD/ R. Macko, MD Adaptive Physical Activity for Chronic Stroke (RC 1)

 Chronic Stroke Survivors

A. Ryan, PhD/ C. Hafer- Macko, MD Aging, Inflammation and Exercise in Chronic Stroke (RC 1, 2, 3,)

 Chronic Stroke Survivors

M. Rogers, PhD, PT, FAPTA Intervention to Enhance Lateral Balance Function and Prevent Falls in Aging (RC 2,3)

Older Adults with and without a Recent Fall

L. Forrester, PhD Ankle Robotic Training after Stroke: Effects on Gait and Balance (RC 2, 3)

 Chronic Stroke Survivors

S. Prior, PhD Aerobic Exercise (AEX) to Improve Regulation of Endothelial Progenitor Cells (EPCs) and Vascular Function in Older Adults with T2DM (RC 1, 2)

Type 2 Diabetes Mellitus

R. Macko, MD; T. Forrester, MD Early Exercise to Improve Muscle and Cardiometabolic Health After Stroke (RC 3)

 Acute Stroke Survivors

S. Seliger, MD, MS; D. Weiner, MD, MS, co-PI Randomized Trial of Exercise Training on Cognitive and Physical Function in CKD (RC 1, 2, 3)

 Chronic Kidney Disease

Recently Funded Trials

Investigator Grant Title

S. Prior Paul B. Beeson Patient-Oriented Research CDA in Aging (K23): Effects of Aerobic Exercise on EPCs and Vascular Dysfunction in Aging and T2DM

K. Oursler/A. Ryan    

VA Merit: Effect of Exercise Training on Inflammation and Function in HIV infected Veterans

M. Serra CDA: Treadmill Rehabilitation, Energy Utilization, and Oxidative Stress in Stroke

J. Russell VA RR&D Merit: Improving Autonomic Function and Balance in Diabetic Neuropathy

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 research related 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.

UM-OAIC Research Career Development Core

• 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”

Current RCDC Jr. Scholars

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)

• Gautam Ramani, 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)

RCDC Jr. Scholars in the Pipeline

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.

Pilot/Exploratory Studies Core (PESC)

• 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.”

2012 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.”

2013 Pilots

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)

• Myerberg Senior 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)