Measuring Physical Resilience in Older Adults Cathleen Colón-Emeric, MD, MHS cathleen.colonemeric@duke.edu We are representing the Duke Pepper Center to talk about our new theme of Understanding Physical Resilience and Reserve in Older Adults.

Objectives Objective 1: Define physical resilience and describe its potential for improving healthspan in older adults.   Objective 2: Describe 3 types of measurement approaches and give examples of how each can be used in geriatric research

Working Definitions Resilience = an individual’s ability to withstand 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) Several of us completed a systematic review on this topic published last fall. We found that A large majority of the literature in this field relates to “psychological resilience” – a personality trait that describes how much control a person feels they have or their will to recover from a trauma. Multiple validated scales of psychological resilience show an association with physical recovery, so while this is not what we are talking about today it is likely an important factor that we need to consider There are currently no accepted definitions of physical resilience – but we identified key features of the current constructs to develop a working definition to move the field forward. Resilience = an individual’s ability to withstand or recover from functional decline following acute or chronic health stressors Because studying resilience at a whole person level becomes very complex, the NIA has started referring to Resliencies - by which they mean recovery of a particular organ system following a specific stressor. Examples – recovery of bone marrow after chemo, recovery of musculoskeletal function after hip fracture Physiologic Reserve = potential capacity of a cell, tissue, or organ system to function beyond its basal level in response to demands (stressors). For example, think of your maximal quadriceps strength vs. the strength required in normal gait. We believe that physiologic reserve constrains resilience at the whole person level

Resilience Simple visual representation of 3 different levels of resilience. The 2 key features are that there must be: A defined physical stress – not just aging itself, and Measurement of some kind of function over time

Related concept of Frailty Resilience is related to, but distinct from the frailty phenotype – a geriatric syndrome characterized by muscle weakness, weight loss, exhaustion, slow gait speed and inactivity. Just as you would rather lean against the bottom wall rather than the top one, you would predict that the man below would recover more quickly from a MI or a surgery than the top patient. However – -the frail and the robust likely represent the tails of the distribution of resilience – all people have some underlying level of resilience -as clinicians we are frequently surprised by how well a frail person, or how poorly a robust person recovers from a stressor – therefore there may be mechanisms underlying resilience that are distinct from those that are deranged in the frailty phenotype.

Geroscience – The Pillars of Aging Why would we hypothesize that resilience might cut across organ systems and be a characteristic at the whole person level? The relatively new field of “geroscience” is based on the observation that aging itself is the predominant risk factor for most diseases. Moreover, interventions that extend lifespan (like caloric restriction or exercise) also delay or prevent many chronic diseases. Geroscience tries to understand how aging enables chronic disease at the cellular/molecular level, so that therapeutic approaches that prevent multiple conditions at once can be developed. Geroscience has described 7 intertwined pathways that are critically involved in the aging process, called the pillars of aging. These pathways occur across cell types and are potentially modifiable. Therefore, if we can identify favorable changes in one or more of the pillars of aging that are associated with better resilience, we have the potential to modify recovery across organ systems and stressor types. From Kennedy et al. Cell 159; 2014

Working Conceptual Model Physical Resilience Outcomes Stressor Pillars of Aging Our working conceptual model is that outcomes after a stressor are determined by ones level of physical resilience. We hypothesize that favorable biology in the pillars of aging result in greater levels of resilience. We also hypothesize that resilience is constrained or moderated by organ reserve, psychosocial factors, and the environment. Certainly the characteristics of the stressor itself are also critical. For example, Rev. and Mrs. B clearly had very different types and duration of physical stress to recover from. Reserve Psychology Social Environment

Measuring Resilience There is not a currently accepted means to measure physical resilience – but all agree that some sort of a recovery trajectory with multiple measures over time is required. One approach is to identify common recovery patterns using simple quartiles or a statistical technique called LCTA. We could follow a cohort of patients undergoing the same stressor over time and identify the 3-6 most common types of recovery patterns, then see which pattern our patient most closely resembles. This example shows different patters of LE function recovery after hip fracture Zimmerman S et al. Arch Phys Med Rehabil 2006;87: 430-6

Measuring Resilience Alternatively, we can use the mathematical features in an individual’s trajectory to quantify level of resilience - the lag time before change, the rate of the change, the amplitude of the change, the time interval between response and stabilization, and the difference in the final state from baseline. Figuring out the optimal ways to measure physical resilience is an area the Pepper Center is actively working on. Adapted from Kirkland JL et al. Resilience in Aging Mice: Proceedings of a workshop at the National Institutemon Aging, In Press (Kirkland, 2016)

Measurement Challenges Define resiliency phenotypes using functional trajectories Individual patient level (Dr. Manning) Population level using (Dr. Prvu-Bettger) Validate cross-sectional measures that predict recovery Clinical tests (Dr. Studenski) Biomarkers (Dr. Belsky)

Discussion and Questions We’re excited about the potential for this model of resiliency to yield new insights that might help older adults recover faster or resist decline after a stressor, and value your ideas on how to move the field forward. We’d like to especially thank all of our colleagues in the Duke Pepper Center. And certainly we thank Rev. and Mrs. B who generously shared their stories with us today. We welcome questions for us or for them.