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Physical Resilience to Health Stressors: Can we Predict and
Promote Recovery?
Heather Whitson, MD, MHSAssociate Professor of Medicine
Deputy Director, Duke Aging Center
All Rights Reserved, Duke Medicine 2007
Objectives
• Define emerging concept of “physical resilience” and its relevance to clinical medicine
• Describe how the “Pillars of Aging” may be related to biological mechanisms that support physical resilience
• List clinical test paradigms that may predict resilience
• Describe intervention strategies to promote resilience
Disclosures: None
PATIENT PRESENTATION
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Mrs Thomas
76 year old woman with obesity, hypertension, arthritis, and history of depression.
She is primary caregiver for her husband who has advanced Parkinson’s Disease.
In February 2016, she was diagnosed with Colon Cancer.
She underwent open colectomy and was foundto have Stage I disease.
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Mr Lee75 year old man with hypertension and history of heart disease status post CABG three years ago. Completed cardiac rehab.
He is a retired attorney. He is married with two adult daughters in the area. He golfs and plays tennis several times a week, though admits his “game isn’t what it used to be.”
In February 2016, he was diagnosed with Colon Cancer.
He underwent lap colectomy (converted to open) and was diagnosed with Stage III disease, necessitating chemotherapy.
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After the Stressor: Mrs. Thomas
0102030405060708090
100
Pre-Stress Discharge 1 mo 2 mo 3 mo
% A
ge
Co
rrec
ted
No
rms
ADL Function 6 min walk LE Functional Scale
Su
rger
y
2
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After the Stressor: Mr. Lee
0102030405060708090
100
% A
ge
Mat
ched
No
rms
ADL Gait Speed TUG
Su
rger
y
Do
se r
edu
ced
20%
Sta
rts
Ch
emo
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Resilience: A Key Ingredient of Health, Across the Lifespan
DEFINITIONS AND CONCEPTS OF PHYSICAL RESILIENCE
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Working Definitions
Physical Resilience = ability to avoid or recover from functional decline following acute or chronic health stressors
Resiliencies = resilience within an organ system to a particular stressor
Reserve = potential capacity of a cell, tissue, or organ system to function beyond its basal level in response to demands (stressors)
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Phenotyping Resilience after the stressor
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What determines recovery trajectories after health stressors?
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Geroscience Initiative – The Pillars of Aging
From Kennedy et al. Cell 159; 2014
7 intertwined and potentially modifiable pathways affected by age
Hypothesis:Favorable biology in these pathways maycut across organ systems to support resilience at the whole-person level.
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Working Conceptual Model
Physical Resilience
Outcomes/Resiliency Phenotypes
Res
erve
Psy
chol
ogy
So
cial
Env
ironm
ent
Pillars of Aging
Stressor
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Resilience is related to the concept of Frailty
Robust
Frail
4
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Resilience is About What Happens After the Stressor
The spectrum from robust to frail may reflect an individual’s degree of physical reserve (potential capacity)
Resilience reflects the actualization of that potential.
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Contrasting Resilience and Frailty:What if potential for recovery is mediated by different mechanisms than the mechanisms that contribute to frailty?
The Metaphor of the Castle Under Siege
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Geroscience – The Pillars of Aging
From Kennedy et al. Cell 159; 2014
Clinical Tests that may indicate level of resilience to some future stressor
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Biomarkers that indicate….?
• Efficient energy management
• Adaptive response to Stress:• Heat shock
proteins• Autophagy
• Well-regulated immune response
• Repair mechanisms
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Predicting Resilience – Provocative Tests
• Stimulus-Response
• Examples in use:– Response to vaccine
– Glucose tolerance test
– Gait lab challenge
– Dual tasking tests
5
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Predicting Resilience – Dynamic physiologic output
Lipsitz et al. JAMA 1992All Rights Reserved, Duke Medicine 2007
Postural Sway Complexity and Falls
Force Platform
Multiple, interconnected inputs = complex output
Zhou et al. Sci Reports 2017
Resilience Promoting Interventions
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Example of Resilience Intervention: STRIDE
Supervised Walking Program for Hospitalized Veterans
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Example of Resilience Intervention: STRIDE
0
1
2
3
4
5
6
Length of stay, median (days)
STRIDE, n=92
Usual Care, n=35
↓ Length of Stay (average of 1 day)↑ Discharge to Home (92% vs. 73%, p =0.007)Annual cost-savings to VA based on bed
days of care: $958,348
Hastings SN et al. J Am Geriatr Soc. 2014 Nov;62(11):2180-4.
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Ultimate Resilience-Promoting Interventions:Healthy Diet and Exercise
Kitzman DW et al. JAMA. 2016;315(1):36-46
RCT of Obese Seniors with HFpEF
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Promoting Resilience : The Platform Metaphor Conclusions
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Ursus WehrliAll Rights Reserved, Duke Medicine 2007
Clinical Take Homes
• Recognize the heterogeneity in resilience to stressors in older adults
• Consider using gait speed and provocative tests to predict resilience
– Biomarkers, complexity tests in the future?
• Consider prehabilitation, encourage healthy diet and exercise for seniors in anticipation of stressors
– Pharmacologic resilience –enhancers in the future?
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Thank you to many collaborators