Conceptual Models

Frailty and failure to thrive

Citation:  Fried LP, Walston J. Frailty and failure to thrive. In: Hazzard WR, Blass JP,  Ettinger WH Jr, Halter JB, Ouslander J, eds. Principles of Geriatric Medicine and Gerontology, 4th Ed. New York: McGraw-Hill; 1998:1387–1402. 

Rationale for a preliminary operational definition of physical frailty and sarcopenia in the SPRINTT trial

In the present article, the rationale that guided the operationalization of the theoretical concept of physical frailty and sarcopenia (PF&S), the condition of interest for the “Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies” (SPRINTT) trial, is presented. In particular, the decisions lead to the choice of the adopted instruments, and the reasons for setting the relevant thresholds are explained. In SPRINTT, the concept of physical frailty is translated with a Short Physical Performance Battery score of ≥3 and ≤9. Concurrently, sarcopenia is defined according to the recent definitions of low muscle mass proposed by the Foundation for the National Institutes of Health-Sarcopenia Project. Given the preventive purpose of SPRINTT, older persons with mobility disability (operationalized as incapacity to complete a 400-m walk test within 15 min; primary outcome of the trial) at the baseline are not included within the diagnostic spectrum of PF&S.

Stimulus-response paradigm for characterizing the loss of resilience in homeostatic regulation associated with frailty

Frailty is a state of health signified by an increased vulnerability to adverse health outcomes in the face of stressors (e.g. infection). There is emerging consensus that research on both the theory and measurement of frailty must focus on the dynamic interactions within and across systems underlying the frailty syndrome. In this paper, we propose a dynamical systems modeling approach, based on the stimulus-response experimental paradigm, to propel future advances in the study of frailty. Our proposal is novel in that it provides a quantitative framework to operationalize and test the core notion underlying frailty that it signifies a loss of resilience in homeostatic regulation. The proposed framework offers many important benefits, including (a) insights into whether and how homeostatic regulation differs between frail and non-frail older adults, (b) identification of critical regulatory systems, if they exist, that could function as sentinel systems for screening and early detection of frailty, (c) establishment of the value of provocative tests that can provide maximal information on the integrity of systems identified in (b), and (d) evaluation and unification of diverse empirical descriptions of frailty by providing a mathematical framework anchored in quantifying the loss of resilience, an essential property of frailty.

Frailty in Older Persons

Citation:  Ferrucci L, Windham BG, Fried LP. Frailty in Older Persons. Genus, 2005; 61(1): 39–53

Dynamics of stability: the physiologic basis of functional health and frailty

Under basal resting conditions most healthy physiologic systems demonstrate highly irregular, complex dynamics that represent interacting regulatory processes operating over multiple time scales. These processes prime the organism for an adaptive response, making it ready and able to react to sudden physiologic stresses. When the organism is perturbed or deviates from a given set of boundary conditions, most physiologic systems evoke closed-loop responses that operate over relatively short periods of time to restore the organism to equilibrium. This transiently alters the dynamics to a less complex, dominant response mode, which is denoted “reactive tuning.” Aging and disease are associated with a loss of complexity in resting dynamics and maladaptive responses to perturbations. These alterations in the dynamics of physiologic systems lead to functional decline and frailty. Nonlinear mathematical techniques that quantify physiologic dynamics may predict the onset of frailty, and interventions aimed toward restoring healthy dynamics may prevent functional decline.

Accumulation of deficits as a proxy measure of aging

This paper develops a method for appraising health status in elderly people. A frailty index was defined as the proportion of accumulated deficits (symptoms, signs, functional impairments, and laboratory abnormalities). It serves as an individual state variable, reflecting severity of illness and proximity to death. In a representative database of elderly Canadians we found that deficits accumulated at 3% per year, and show a gamma distribution, typical for systems with redundant components that can be used in case of failure of a given subsystem. Of note, the slope of the index is insensitive to the individual nature of the deficits, and serves as an important prognostic factor for life expectancy. The formula for estimating an individual’s life span given the frailty index value is presented. For different patterns of cognitive impairments the average within-group index value increases with the severity of the cognitive impairment, and the relative variability of the index is significantly reduced. Finally, the statistical distribution of the frailty index sharply differs between well groups (gamma distribution) and morbid groups (normal distribution). This pattern reflects an increase in uncompensated deficits in impaired organisms, which would lead to illness of various etiologies, and ultimately to increased mortality. The accumulation of deficits is as an example of a macroscopic variable, i.e., one that reflects general properties of aging at the level of the whole organism rather than any given functional deficiency. In consequence, we propose that it may be used as a proxy measure of aging.

The physics of frailty

The contribution of frailty to human morbidity and mortality is immense. Yet it lacks a conceptual framework. By borrowing from the hypotheses provided by the thermophysicists, frailty can be understood in a way that both interrelates the relationship between form and function and provides medical science with an operational insight that yields clinical benefit.

Frailty results where the organism is uncoupled from its environment yielding a break in the forward feedback cycle of stimulus to reaction to growth to increased functional competence to improved response to stimulus. Recognition of the centrality of this interrelatedness to health becomes a key theme for illness prevention and therapy.

Preventing frail health

Frailty is a state of reduced physiologic reserve associated with increased susceptibility to disability. Reduced physiologic capacity in neurologic control, mechanical performance, and energy metabolism are the major components of frailty. Although disease is an important cause of frailty, there is sufficient epidemiologic and experimental evidence to conclude that frailty is also due to the additive effects of low-grade physiologic loss resulting from a sedentary lifestyle and more rapid loss due to acute insults (illness, injuries, major life events) that result in periods of limited activity and bedrest. The pathogenesis of frailty involves a complicated interaction of factors that block recovery from rapid physiologic loss. To some extent, frailty is preventable. Approaches to prevention include (1) the periodic monitoring of key physiologic indicators of frailty, (2) the prevention of physiologic loss and acute and subacute episodes of physiologic loss, (3) the prediction of episodes of physiologic loss and the reduction of frailty prior to the loss, and (4) the removal of obstacles to recovery once physiologic loss has occurred.