Advancing the visibility of frailty research: Upcoming spotlight on novel and exciting research questions 

The term “frail” has evolved from a catch-all phrase to describe older persons with a wide range of health conditions to a more refined set of theories and definitions that aim to characterize systemic vulnerability to poor health outcomes. Research on frailty has flourished in recent years, and this growing energy to study and utilize our understanding to best improve the health of older adults sits at a tipping point that we believe can benefit from a targeted focus on existing gaps in our frailty-related knowledge.
To this end, BMC Geriatrics has announced a call for a collection of papers focused on frailty research: https://bmcgeriatr.biomedcentral.com/frailty. Categories include: Epidemiology and Measurement; Frailty Biology; Frailty and Clinical Care; and Interdisciplinary Topics. As noted in a recent editorial, there are four topics  highlighted in hopes of advancing the field toward tackling novel and exciting research questions:
1)    Causes of frailty, distinguishing by primary, biologically-driven causes or secondary disease-driven processes that lead to frailty.
2)    Innovative interventions, including targeting frailty itself as well as approaches for care delivery for frail persons
3)    Biological studies of novel biological mechanisms responsible for the generalized physiological dysregulation associated with frailty, specifically omics-based studies
4)    Integrated solutions beyond clinical medicine for identifying and managing frailty
The call for papers for the Frailty collection is open now; please consider submitting your research!
The full editorial by the collection’s Guest Editors, Prof. Ivan Aprahamian and Dr. Qian-Li Xue, is available here: “Shaping the next steps of research on frailty: challenges and opportunities.”

The Geriatric Surgery Program at Johns Hopkins

Johns Hopkins Bayview Medical Center (JHBMC) annually performs surgical procedures on more than 600 patients over the age of 65, with nearly one-third of these patients identified as frail and at high-risk for adverse outcomes.  It is currently the goal of JHBMC to be the national leader in discovering how to bring our older patients through surgery safely, preserve quality of life, and return them to their loved ones as soon as possible.

The first step in mitigating the impact of frailty on surgical outcomes is being able to recognize who is vulnerable. JHBMC has been a leader in the affirmation and implementation of best practice guidelines put forth by the American College of Surgeons and the American Geriatric Society for the care of the older surgical patient. JHBMC participated in a national survey to examine what resources were most needed for the care of the older frail surgical patient. In addition, JHBMC along with seven other institutions was asked to examine best methods for implementation of a Geriatric Surgery Care Pathway that incorporates the best practices outlined by these societies. This project included setting both national standards and individual pathways for the perioperative care of the vulnerable older adult patient and ultimately, designating hospitals that participate in these pathways as “Centers of Excellence.”

Effective care pathways are not new to the care of surgical patients at JHBMC. In 2015, JHBMC implemented an Enhanced Recovery Pathway (ERP) for patients undergoing major abdominal surgery.  Surgical outcomes for major abdominal procedures following the implementation of our ERP have resulted in a significant reduction in length of stay (2 days), a 50% reduction in hospital-acquired complication, and a 9% increase in patient satisfaction following major abdominal procedures (Sateri et al., 2017).  In 2018, JHBMC implemented a multidisciplinary, hospital-wide, Geriatric Surgery Pathway, and Figure 1 below is a schematic of our pathway.  We recently examined our outcomes from the past 3 years following implementation.  We have seen a significant (over 70%) reduction in discharge to skilled nursing facilities following surgery and a 30% reduction in postoperative complications (Mostales et al., 2021; see page S205).

The following short video provides an overview of the surgical care experience at JHBMC.

Dr Sally Gearhart in Bayview Geriatric Med Vid

(Click on the image to view the video.)

To learn more about surgery in frail older patients, please see the Clinical Topics section on Surgery and Frailty.

Understanding the etiology underlying frailty: Making frail older adults less frail 

Why do older adults grow frail? 

Because they grow old–but not only this. We all know, or we recognize as researchers, that some octogenarians thrive, while others ten years younger are highly vulnerable. 

Our field of gerontology often asks a different question: How should an older adult’s frailty influence the care we provide them? That’s important. So also, though, is to treat the frailty itself: truly treat, and not just ameliorate symptoms. This is what any one of us would wish if we were frail—to not be as frail anymore. 

Our group here at Frailty Science has been pursuing the goal of forestalling and turning back frailty for more than two decades. Which brings us back to the question where we began—why do older adults grow frail? If we knew the answer, maybe we could reverse the process: at least, take it a few steps back. The evidence base we have accrued points to a potential answer: People become physically frail because their physiology reaches a pattern and threshold of dysregulation making it impossible to sustain, even qualitatively, its intended functioning. 

You can imagine how thrilled and privileged we felt recently, then, when Nature Aging published a compendium of our work in its inaugural issue. In brief, we hypothesize that frailty results from critical dysregulation in multiple physiological systems—not any systems, but a few specific systems that are central to stress response, musculoskeletal integrity, and energy metabolism. Dynamical systems theory may then provide a useful lens to recognize impending critical transitioning out of qualitatively “normal” physiological functioning, and emergence into a radically different, frail state of functioning. The component systems—stress response and etc.—would be “modules” in the overarching dynamical system, and then their integrity, protocols for interacting with each other, preservation of redundancies against failures, and the like are parameters governing the overarching functioning. Elegant mathematics are available to characterize these parameters: We believe the parameters’ estimation in the context of stressor perturbation hold promise both as biomarkers of frailty and levers to identify intervention points that could indeed turn back frailty—at least, frailty below a severity threshold where intervention remains possible.  

If you’re interested, we hope you’ll check out this work further: 

Nature Aging Article  

Johns Hopkins Press Release

Frailty and Cognitive Impairment: Time to Acknowledge and Embrace Heterogeneity

Frailty and cognitive impairment, two common geriatric conditions, are known to be associated with late-life vulnerability in older adults (Todd et al., 2013Cesari et al., 2016Fried et al. 2001). An estimated 15% of non-nursing home older adults in the United States aged 65 and over are frail (Bandeen-Roche et al., 2015), and about 22% and 9% have mild cognitive impairment and dementia (Katz et al. 2012Langa et al., 2017). Physical frailty and cognitive impairment often co-exist in older adults. However, there are sizeable subgroups who have one but not the other. According to a recent US population-based study published in the Journal of the American Geriatrics Society by Ge and colleagues (Ge et al., 2020), 67% of frail older adults had cognitive impairment, and 29% of older adults with cognitive impairment were frail. That physical frailty and cognitive impairment may not manifest together is reinforced by clinical encounters with older adults who are physically robust but cognitively frail and vice versa. 

The study by Ge et al. also found that individuals with frailty only (meaning without cognitive impairment) had the highest prevalence of obesity, current smoking, multimorbidity, lung disease, and history of surgery. The group with both cognitive impairment and frailty were the oldest on average and had the highest prevalence of dementia, depression, cardiovascular diseases, and disability. It is also worth noting that the prevalence of dementia in the group with both frailty and cognitive impairment was more than doubled compared to the group with cognitive impairment alone. This latter finding makes it plausible that the comorbid status could result from frailty being a sequela of cognitive impairment beyond a certain severity. Alternatively, the joint versus separate occurrence of frailty and cognitive impairment may signal different etiologies and pathways. Preliminary support of the latter came from a recent longitudinal study showing that people on a trajectory to develop dementia were three times more likely to experience concurrent onset of frailty and cognitive impairment than to develop cognitive impairment first (Chu et al., 2019). Taken together, these findings suggest that the co-occurrence of cognitive impairment and frailty may be driven primarily by neurologic pathologies rather than “normal” cognitive aging or physical impairments. By contrast, the group with cognitive impairment only may represent mostly normal cognitive aging with less disease burden, as shown in the study by Ge et al.

The findings above support the value of assessing frailty and cognitive impairment in tandem in clinical settings in order to achieve greater measurement specificity as well as inform the selection and prioritization of treatment targets. For example, the group with frailty only may benefit from tailoring interventions based on specific disease profiles. In contrast, the group with cognitive impairment only may largely reflect non-pathological cognitive aging given their lower dementia prevalence and multimorbidity burden (cardiovascular diseases in particular), and therefore may benefit from lifestyle interventions. The group with comorbid frailty and cognitive impairment on the other hand may benefit from interventions that target both dementia-related pathologies and vascular risk factors to slow down the progression of dementia and the accompanying diseases. Now is the time to embrace a paradigm shift from pursuing research on frailty and cognitive impairment in silos to an integrative and holistic approach by which precision medicine can succeed in caring for older adults.

Double Jeopardy for Older Adults of Color: An Urgent Call to Address Frailty Disparities in the United States

Karen Bandeen Roche, PhD
Karen Bandeen Roche, PhD

Frank Hurley and Catharine Dorrier Chair of Biostatistics
Johns Hopkins Bloomberg School of Public Health
Co-Director, Johns Hopkins Older Americans Independence Center

Sarah Szanton, PhD, MSN, RN
Sarah Szanton, PhD, MSN, RN

FAAN, ANP
Professor
Endowed Professor for Health Equity and Social Justice
Director, Center for Innovative Care in Aging

Roland Thorpe, Jr., PhD
Roland Thorpe, Jr., PhD

Co-Director DrPH Concentration in Health, Equity, and Social Justice
Professor

Racial inequality that has been embedded in US structures and institutions has been exposed by twin catastrophes of 2020. In the height of the early novel coronavirus pandemic, Black, Latinx, and Native Americans were roughly 5 times as likely to be hospitalized for COVID-19 than their white peers, and Black Americans were twice as likely to die as whites (CDC COVID-19 Hospitalization by Race/Ethnicity, accessed 11/18/20). The killing of George Floyd, Ahmaud Arbery, Breonna Taylor, and others highlight the fact that people of color in the US continue to disproportionately experience police and vigilante violence along with other forms of inequality, including substandard housing, under-resourced schools, and restricted access to living-wage employment.

As one observes that highly publicized disparities in health and safety disproportionately affect young and middle-aged individuals, it can be tempting to predict that inequities lessen or even out in old age. Some have argued this (Meich, 2009). Motivated by studies we have performed as well as others’, we fear that such an approach—whether arising from complacency or misunderstanding—will leave older people of color in America with considerably diminished quality of life and heightened risk of other adverse outcomes. Frailty is a case in point. In a study to evaluate national racial/ethnic prevalence disparities, we found that the odds of frailty among non-Hispanic Black and Hispanic older adults were inflated approximately 1.5 times compared to non-Hispanic White older adults, after adjusting for age, sex, income, BMI, and comorbidity (Usher et al., 2020). Relative to a non-Hispanic white sociodemographic group with 15% prevalence—likely a quite typical group, given an estimated overall national prevalence of 15.3% (Bandeen-Roche et al., 2015)–this translates into prevalence of roughly 21% for non-Hispanic Blacks and Hispanics.  We further found that, for Black older adults, relative Black versus white disparities were comparable across income quartiles (and the estimated percentage inflation in frailty odds actually was greatest in the highest income quartile). This means that intersectionality looms large; added risks appear to aggregate when under-represented race/ethnicity and economic disadvantage are taken together.

Disparities in frailty experience may provide a particularly telling case because of implications for other risks as well as for mechanisms leading to the disparity in older age.  The studies described above employed physical frailty phenotype (PFP) ascertainment of frailty. Under the PFP paradigm, frailty is hypothesized as a clinically recognizable syndrome arising from critical dysregulation in physiological systems governing energy production and use as well as stress response, resulting in vulnerability to adverse outcomes following stressors (Fried et al., 2001; Bandeen-Roche et al., 2020). With heightened frailty prevalence, older Americans of color or minority ethnicity may disproportionately frequently experience amplified physiological vulnerability together potentially with impaired access to resources by which to compensate, leading to a vulnerability “double-hit” putting them at particularly amplified risk for adverse outcomes. Considering frailty as an outcome of unraveling stress response regulation, moreover, may provide insight into mechanisms leading to such a large race disparity in frailty in late life; stress response stands to be impaired with chronically elevated stress over the life course, and this is exactly what one might hypothesize to follow from the persistent experience of socioeconomic inequities, social injustice, and structural racism. It is the inextricably intertwined historical context and life experiences that many older Black Americans have endured that position their bodies for poor outcomes, such as frailty. 

It follows that the need for research to discover the etiology of late life frailty, and then to intervene on or buffer it, is particularly urgent for reducing racial/ethnic disparities in the health and well-being of older Americans. Meanwhile, efforts to buffer the implications of frailty for older Americans need not wait. Interventions with proven effectiveness for reducing stressors in the home environment already exist;  CAPABLE, an evidence-based program which provides tailored occupational therapy, nursing, and handy worker services to enhance function of older adults aging at home and prevent costly institutional care, is a strong example of these. Programs and policies to reduce disparities in opportunity to maintain good health also could have high impact. These are needed to address health facilitators that are unavailable to many older adults of color, including ready transportation by which to access health care, high-quality nutrition, and neighborhood environments in which to safely engage in physical activity—all essential to staving off frailty and reducing its impact. If feasibility mandates, these interventions could be targeted—for example, using methods to assess pre-frailty pioneered by our Older Americans Independence Center as well as other groups. Screening to identify pre-frail and frail older Americans of color could not be more timely in the face of the COVID-19 pandemic. We suspect that the etiology underlying frailty intersects considerably with the etiology of susceptibility to the novel coronavirus, and conversely infection may contribute to future frailty. Finally, whether to bolster robustness and resilience in the short term or for protection against future health threats, addressing frailty among older Americans of color is a matter of the highest import for researchers, clinicians, and policymakers alike.