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.