Frailty in Older Adults

Frailty is a clinically identifiable state of diminished physiologic reserve and increased vulnerability to a broad range of adverse health outcomes.^1–5 Frailty becomes more common as populations age. In a report covering 62 countries world-wide, the prevalence of frailty in community-dwelling persons ranged from 11% in those aged 50–59 years to 51% in those aged 90 years or older.⁶ Older people in acute care hospitals and nursing homes, those in low- and middle-income countries, and those with a socially vulnerable status are all at increased risk for frailty.⁷

Here, we first provide a brief overview of frailty, including its biological mechanisms, measurement, and clinical management. This is followed by a discussion on approaches to individualize clinical management based on patients’ frailty levels and interventions to improve frailty and associated health outcomes. Lastly, we suggest current evidence gaps and future directions for managing frailty at scale in our aging society.

DEFINITIONS OF FRAILTY

Despite the existence of various definitions, two concepts of frailty predominate: frailty as a syndrome, and frailty as a state. Each becomes more common with age and predicts adverse health outcomes.^1,2 Notably, they identify different population subsets as frail. The Fried physical frailty phenotype^2,8 sees a clinical syndrome resulting from altered metabolism, coupled with abnormal stress responses. Characteristic features are: exhaustion (first manifestation), weakness, slowness, physical inactivity, and weight loss (last manifestation).⁹ The degree of frailty is determined by the number of features present: “robust” if none, “pre-frail” if 1–2 features, and “frail” if 3–5 features. Having all five features indicates a critical transition. Mortality rises sharply, and the chance of reversal diminshes.¹⁰ The Fried physical frailty phenotype is distinct from multimorbidity and disability.¹¹

Frailty as deficit accumulation defines a state of poor health from accumulating age-related health deficits.^1,12 Deficit selection depends on the context and available information (e.g., survey, comprehensive geriatric assessment, electronic medical records, administrative data, or biomarkers) and can include diagnoses, cognitive and physical function, disability, nutritional status, or laboratory tests. The degree is quantified by a frailty index, which is the proportion of deficits present out of the number of deficits assessed. It should include at least 30 deficits.¹ In most studies, less than 1% of people have a frailty index greater than 0.70, suggesting a deficit burden that threatens survival.¹ Despite calls for a “once-and-for-all” consensus,¹³ both the Fried physical frailty phenotype and deficit accumulation frailty approaches remain in use.

BIOLOGY OF FRAILTY

The current understanding of the biological mechanisms of frailty is evolving and incomplete.^1,2,14 It is thought that a process of accelerated aging at subcellular and cellular levels, including chronic inflammation, cellular senescence, mitochondrial dysfunction, and deregulated nutrient-sensing,^15,16 give rise to dysfunction in multiple physiological systems and then to clinical manifestations of frailty. Whether targeting these biological processes can prevent or reverse frailty is an active area of investigation. As most studies to date are preclinical, it remains uncertain how these findings may translate to humans.

Chronic inflammation, which may occur in response to non-infectious triggers such as cellular senescence and mitochondrial dysfunction, inhibits growth factor expression and increases catabolism, thereby contributing to sarcopenia and frailty.¹⁷ Genetically altered mice that cannot produce the anti-inflammatory cytokine interleukin-10 exhibited higher serum interleukin-6 levels, reduced oxygen consumption, and muscle weakness.¹⁸ Triggered by DNA damage, cancerous mutations, and oxidative stress, some cells enter a state of permanent cell cycle arrest (cellular senescence), during which they remain viable and secrete proinflammatory molecules (the senescence-associated secretory phenotype).¹⁹ Senolytic agents, such as dasatinib and quercetin, remove senescent cells, leading to reduced inflammation and metabolic dysfunction in obese mice, improved lung compliance and reduced frailty in mice with idiopathic pulmonary fibrosis, and restoration of age-related bone loss in mice.¹⁹ Chronic inflammation may also attenuate immune responses,²⁰ increasing susceptibility to infections and impairing antibody response after vaccines.

Another key mechanism implicated in the development of frailty is mitochondrial dysfunction, caused by mutations in mitochondrial DNA, destabilization of respiratory chain complexes, and disruptions in mitochondrial homeostasis. The consequences are decreased cellular energy production, increased production of reactive oxygen species, and inflammation.¹⁴ Superoxide dismutase-1 knock-out mice, which suffer from high levels of oxidative stress, showed weight loss, muscle weakness, physical inactivity, and exhaustion, which was attenuated by dietary restriction.²¹ In humans, mitochondrial dysfunction in skeletal muscle was associated with muscle weakness, exercise intolerance, and fatigue.²² Lower numbers of mitochondrial DNA copies, a marker of mitochondrial depletion, were correlated with the Fried physical frailty phenotype²³ and deficit accumulation frailty.²⁴

Deregulated nutrient sensing is also implicated in how frailty arises. Nutrient-sensing pathways involve mammalian target of rapamycin complex-1 (nutrient sensor) as well as adenosine monophosphate-activated protein kinase and sirtuin-1/3 (nutrient scarcity sensor).¹⁶ By turning on adenosine monophosphate-activated protein kinase and sirtuin pathways and inhibiting the mammalian target of rapamycin pathway, caloric restriction offers health and longevity benefits.²⁵ In rhesus monkeys, long-term caloric restriction prevented the Fried physical frailty phenotype and improved muscle weakness, slowness, physical inactivity, and exhaustion compared with ad libitum intake.²⁶ Inhibiting the mammalian target of rapamycin pathway with rapamycin, activating adenosine monophosphate-activated protein kinase with metformin, or activating surtuin-1/3 with a nicotinamide adenine dinucleotide precursor improved muscle mass and function in animal models.¹⁴

Aging is associated with hormonal changes, such as a decline in anabolic hormones (e.g., dehydroepiandrosterone sulfate, testosterone, and growth hormone/insulin-like growth factor-1) and an increase in catabolic hormones (e.g., cortisol).¹⁴ These hormonal changes inhibit skeletal muscle growth and promote breakdown and may contribute to loss of resilience (ability to recover from a stressor) and frailty.

MEASUREMENT OF FRAILTY

Many instruments are available for measuring frailty. Most frailty tools predict adverse health outcomes, and brief screening tools abound for use in outpatient, inpatient, emergency department, and preoperative clinics. These may employ self-report (e.g., Fatigue, Resistance, Ambulation, Illnesses, and Loss of Weight questionnaire²⁷), clinical judgment (e.g., Clinical Frailty Scale²⁸) or electronic medical records.²⁹ Gait speed (<0.8 meters/second) has 99% sensitivity for detecting the Fried physical frailty phenotype.³⁰ However, simple tools rarely provide information sufficient to mitigate risk through individualized care plans or tailored interventions. Multidomain tools based on comprehensive geriatric assessment (e.g., deficit accumulation frailty index,¹ Edmonton Frail Scale³¹) can reveal reversible conditions or target domains for interventions. Comprehensive geriatric assessment is a multidimensional evaluation performed by a multidisciplinary team or an expert clinician that aims at determining an older person’s medical, functional, physical, psychological, and socioenvironmental status to develop a coordinated and integrated plan for treatment and follow-up (see details on comprehensive geriatric assessment in Online Supplement). For decision-making about stressful treatments (e.g., chemotherapy or surgery), tools tested in those specific treatment populations might better predict treatment outcomes than do more general tools. A guide for choosing a frailty assessment tool and electronic calculators for commonly used tools are available at eFrailty.org

Performance measures (e.g., gait speed, handgrip strength) can be affected by acute conditions or may be impractical in hospital settings. If so, tools that do not involve performance testing can be useful. To avoid attributing symptoms of acute illness to frailty, evaluation should inquire about health status in the recent past (e.g., two weeks before), not at the time of assessment. Knowledge of prior frailty status can reveal an older person’s health trajectory, and could form the basis of an annual review.³² Worsening trajectories of Fried phenotypic frailty and deficit accumulation frailty are associated with higher mortality risk^9,32 and decline in quality of life.³³ Caution should be used when comparing results from different frailty tools. Modifying the Fried physical frailty phenotype³⁴ or using different deficit compositions of a frailty index,³⁵ often done in measuring context-specific health states (e.g., surgical settings), can give inconsistent results. To avoid misinterpretation, the frailty tool used should be specified. Guidelines are available to allow comparison between commonly used frailty tools.³⁶

EVIDENCE FOR UTILITY OF FRAILTY SCREENING AND MANAGEMENT

The current evidence for frailty screening and interventions is limited. Most clinical trials evaluating frailty interventions have small sample sizes, heterogenous study populations, use variable frailty tools, and have differences in interventions and outcome measures, all of which contribute to lower quality evidence.^37–41 Despite these limitations, certain interventions have been demonstrated to improve frailty and associated outcomes (e.g., mobility, muscle strength, functional status, falls) (Table 1). Although frailty assessment was used to determine eligibility in these trials, uncertainty remains regarding the effectiveness of routine frailty screening in improving patient outcomes and reducing healthcare utilization and costs, as compared to usual care in primary care settings. The utility of frailty screening has been best demonstrated in oncology^42,43 and surgery.^44,45 The interventions that have proven efficacious in the controlled environment of clinical trials have not consistently shown similar effectiveness in more pragmatic, routine care settings.^46,47 Rather than concluding a lack of efficacy, more effort is needed to understand how to best implement these interventions and translate their benefits into routine care.

Table 1.

Summary of Evidence on Interventions to Prevent or Improve Frailty and Associated Clinical Outcomes^*

Intervention	Clinical Setting and Evidence	Comments
Exercise	Community-dwelling older persons at risk of frailty Exercise with nutrition intervention may improve Fried frailty phenotype (low certainty).37 Exercise likely improves mobility (moderate certainty) and may improve Fried frailty phenotype (low certainty), ADL (low certainty), and SOF scale (very low certainty). Its effect on falls is uncertain (very low certainty).38 Yoga likely improves mobility and muscle strength (moderate certainty) and may improve balance (low certainty).40	Most evidence exists for resistance training. Optimal exercise program is unknown; a typical exercise program involved aerobic exercise and muscle strengthening, with 30–60 minutes/session x 1–4 sessions/week.38 Exercise in hospitalized older patients was typically supervised by a physical therapist, focusing on resistance training, with 20–90 minutes/session x 2–5 sessions/week.63 Exercise in hospitalized older patients did not increase falls.64
	Community-dwelling older persons with frailty Exercise with nutrition intervention may improve Fried frailty phenotype (low certainty) and mobility (very low certainty). Its effect on ADL is uncertain (very low certainty).37 Exercise likely improves mobility and ADL (moderate certainty) and may improve Fried frailty phenotype (low certainty) and Edmonton Frail Scale (very low certainty).38 Tai Chi may improve muscle strength (low certainty) and balance (very low certainty) and may reduce falls (low certainty). Its effect on mobility is uncertain (very low certainty).41
	Hospitalized older patients Exercise with nutrition intervention may improve Fried frailty phenotype (low certainty), deficit accumulation frailty (very low certainty), mobility (very low certainty), and ADL (very low certainty). Its effect on falls is uncertain (very low certainty).63 Exercise may not improve ADL (low certainty). Its effect on mobility is uncertain (very low certainty).64
	Nursing home residents Exercise may improve mobility (very low certainty). Its effect on ADL and falls is uncertain (very low certainty).38 Yoga may improve balance (very low certainty). Its effect on mobility and muscle strength is uncertain (very low certainty).40
Nutrition	Community-dwelling older persons at risk of frailty Nutritional supplement (ONS or fortified foods) may improve Fried frailty phenotype (low certainty) and ADL (very low certainty). Its effect on mobility and mortality is uncertain (very low certainty).37,65 Vitamin D supplementation does not improve mobility (high certainty) and may not improve muscle strength (low certainty) or deficit accumulation frailty (very low certainty). Its effect on Fried frailty phenotype is uncertain (very low certainty).55–57 Omega-3 supplementation may not improve mobility (low certainty), muscle strength (very low certainty), or deficit accumulation frailty (very low certainty). Its effect on Fried frailty phenotype is uncertain (very low certainty).56,57,59	The recommended dietary allowance for protein intake 0.8 g/kg/day may be inadequate in older persons due to anabolic resistance. Experts recommend 1.0–1.2 g/kg/day for healthy older persons and 1.2–1.5 g/kg/day for those with acute or chronic illness and at risk for malnutrition, except for those with chronic kidney disease.72 Protein ingestion in temporal proximity to resistance exercise may induce greater muscle protein synthesis.73
	Community-dwelling older persons with frailty Nutritional supplement (ONS or fortified foods) alone may improve Fried frailty phenotype (low certainty) and mobility (very low certainty). Its effect on ADL is uncertain (very low certainty).37 The effect of vitamin D supplementation on muscle strength is uncertain (very low certainty).58
	Hospitalized older patients Nutritional supplement (ONS or fortified foods) alone may improve mobility (very low certainty). Its effect on muscle strength, ADL, mortality, and hospitalization is uncertain (very low certainty).65
	Nursing home residents The effect of nutritional supplement (ONS or fortified foods) alone on muscle strength, ADL, mortality, and hospitalization is uncertain (very low certainty).65 The effect of vitamin D supplementation on muscle strength is uncertain (very low certainty).58
CGA and multidisciplinary intervention	Community-dwelling older persons at risk of frailty CGA and multidisciplinary intervention lower the risk of Fried frailty phenotype (high certainty).39	CGA is a systematic and multidimensional evaluation focused on determining a frail older person’s medical, functional, physical, psychological, and socioenvironmental status to develop a coordinated and integrated plan for treatment and follow-up. CGA in the inpatient setting is delivered by a specialist team or in a dedicated care unit.
	Community-dwelling older persons with frailty CGA and multidisciplinary intervention improve Fried frailty phenotype (high certainty) and may reduce unplanned hospitalization (low certainty). They do not reduce nursing home admission (high certainty) and are unlikely to reduce mortality (moderate certainty). Their effect on emergency department visits is uncertain (very low certainty).39,47
	Hospitalized older patients CGA reduces nursing home admission (high certainty) and likely increases home discharge (moderate certainty).39 In patients admitted with acute medical condition or injury, CGA reduces hospital falls (high certainty).39 In patients with hip fracture trauma, CGA reduces delirium (high certainty), likely improves mobility (moderate certainty), may reduce mortality (low certainty), and may improve ADL (very low certainty).39 In non-orthopedic surgical patients, CGA likely reduces delirium (moderate certainty).39 In emergency surgical patients, CGA likely reduces mortality (moderate certainty).39
Medication optimization (comprehensive medication review and deprescribing)	Community-dwelling older persons at risk of frailty Medication optimization may reduce mortality (low certainty). It is unlikely to reduce hospitalization (moderate certainty) and may not reduce falls (low certainty).53	The American Geriatrics Society Beers criteria74 and the STOPP/START criteria75 can be helpful for medication optimization. Comprehensive medication review is often part of CGA.
	Community-dwelling older persons with frailty Medication optimization may reduce functional decline (very low certainty). Its effect on falls is uncertain (very low certainty).54
	Hospitalized older patients Medication optimization may reduce emergency department visits (very low certainty) but may not reduce hospitalization (low certainty). Its effect on ADL, falls, delirium, and mortality is uncertain (very low certainty).66
	Nursing home residents Medication optimization reduces falls (high certainty), mortality (high certainty), and hospitalization (high certainty). It may improve Edmonton Frail Scale (very low certainty).54,67
Hormone supplementation	Community-dwelling older persons at risk of frailty Testosterone supplementation may improve mortality (low certainty) but it may not improve mobility (low certainty). Its effect on Fried frailty phenotype or deficit accumulation frailty is uncertain (very low certainty).60 The effect of estrogen and progesterone replacement on mobility and muscle strength is uncertain in postmenopausal women (very low certainty).61 The effect of growth hormone supplementation on muscle strength is uncertain (very low certainty).62
	Community-dwelling older persons with frailty The effect of testosterone supplementation on mobility is uncertain (very low certainty).60

Abbreviations: ADL, activities of daily living; CGA, comprehensive geriatric assessment; ONS, oral nutritional supplement; SOF, study of osteoporotic fracture.

^*Overall, high-quality evidence for frailty interventions is limited. The quality of evidence was evaluated by the authors based on selected meta-analyses and randomized controlled trials according to the Grading of Recommendations, Assessment, Development, and Evaluations framework.

Approach to Frailty-Guided Clinical Management

The concept of frailty can be a useful tool in clinical practice, enabling clinicians to predict prognosis and risk for age-related health conditions; target the delivery of evidence-based interventions; and tailor clinical management, including decisions about stressful treatments (e.g., chemotherapy, major surgery). Considering an older person’s degree of frailty on a fit-to-severely-frail spectrum can usefully frame how to apply evidence and geriatric care principles (Figure 1). The goal is twofold: 1) increase physiologic reserve to build robustness (minimize damage from stressors) and resilience (repair damage) and 2) prevent or mitigate stressors. Management of individuals without frailty should focus on increasing physiologic reserve through healthy lifestyle, chronic disease management, and preventive care.

Figure 1. A Proposed Approach to Clinical Management of Older Patients Based on the Degree of Frailty.

Abbreviation: CGA, comprehensive geriatric assessment; FI, frailty index.

The proposed approach by the authors combines the evidence from randomized controlled trials and best practices of geriatric care, both of which are necessary to provide evidence-based, person-centered care to older adults across the fit-to-frail spectrum. It should be used as a guide as appropriate based on clinical evaluation. For fit or pre-frail individuals, clinical management should focus on increasing physiologic reserve and managing chronic conditions to prevent long-term negative health effect, including frailty and disability. For individuals with frailty, the management should focus on preserving physiologic reserve and preventing or mitigating stressors. Because these individuals have multimorbidity and polypharmacy, it is often necessary to align treatment to the patient’s personal goals and preferences. As an individual approaches end-stage frailty (i.e., having all 5 features of Fried frailty phenotype, a deficit accumulation frailty index near 0.7, or complete dependence in personal care), the management needs to focus on providing comfort and dignity. The frailty score cutpoints are reasonable estimates, not meant to be used as strict rules. When first applying these cutpoints in clinical practice or research, adjustment to the clinical context may be necessary. Management should be guided by patients’ goals and preferences, and frailty should not be used to prevent access to potentially effective treatments.

For individuals suspected to have frailty, a careful medical evaluation or comprehensive geriatric assessment is needed to identify precipitants and exacerbants and determine targets for interventions. Potentially high-yield clinical targets are depression, anemia, hypotension, hypothyroidism, vitamin B12 deficiency, unstable medical conditions, and adverse drug events.⁴⁸ Management aims to preserve physiologic reserve and prevent stressors to maximize function and quality of life, guided by the patient’s goals and degree of frailty. An important part of that should include making routine care less hazardous, a burden that, due to their greater vulnerability, often falls on older people who live with frailty. Frailty should not be used as a convenient way to withhold potentially effective treatments, rather as a tool to facilitate a patient-centered care. Aligning treatment to the patient’s health priorities may reduce treatment burden and unwanted care.⁴⁹ While the effort to minimize polypharmacy and potentially inappropriate medications is necessary, some treatments (e.g., exercise⁵⁰) may provide greater benefit to those with frailty. Incorporating frailty into a prognostic model improves life expectancy estimation and thereby help guide decisions about cancer screening.⁵¹ Personalized, adaptive coping strategies, such as keeping daily routines in familiar surroundings, maintaining social connections, and mobilizing resources, can help patients perform self-care and continue social roles, despite the limitations imposed by frailty.⁵²

Identifying individuals with frailty nearing the end of life (end-stage frailty) can be challenging due to unpredictable patterns of functional decline. These individuals often exhibit all features of the Fried physical frailty phenotype,¹⁰ a deficit accumulation frailty index approaching 0.70,¹ or complete dependence in personal care.²⁸ Management can focus on providing comfort and dignity including palliative care and hospice care.

As frailty progresses, social support is important to ensure adherence to care plans and to assist with health management and daily activities. Due to the heightened vulnerability, vaccination and home environment modification are crucial ways to prevent avoidable stressors.

Interventions for Frailty

We summarize the evidence from meta-analyses and systematic reviews of randomized controlled trials of interventions to prevent or improve frailty and associated outcomes by clinical settings (Table 1). Generally, interventions efficacious in improving frailty (e.g., exercise and comprehensive geriatric assessment) impact a range of physiological systems, whereas interventions (e.g., hormone therapy) that narrowly target a single physiological abnormality have not shown efficacy.

In community-dwelling older persons, exercise and oral nutritional supplementation, either alone or combined,^37,38 and comprehensive geriatric assessment³⁹ may have a positive effect on the Fried physical frailty phenotype. Exercise interventions, typically involving aerobic exercise and muscle strengthening at a frequency of 1–4 sessions per week for 30 to 60 minutes each,³⁸ as well as Yoga^38,40 and Tai Chi,^38,41 likely enhance mobility and muscle strength, improve activities of daily living, and reduce falls. Comprehensive geriatric assessment may prevent unplanned hospitalization without affecting the risk of nursing home admission or mortality in people with frailty.^39,47 Medication optimization, which includes comprehensive medication review and dose reduction or discontinuation of medications with harmful effects or unclear benefits, may reduce mortality⁵³ and functional decline.⁵⁴ Supplementation of vitamin D,^55–58 omega-3,^56,57,59 sex hormones,^60,61 and growth hormone⁶² had little effect on frailty, physical function, and activities of daily living.

In hospitalized older patients, exercise with oral nutritional supplementation may improve the Fried physical frailty phenotype, deficit accumulation frailty, mobility, and activities of daily living.⁶³ Exercise alone or oral nutrition supplementation alone has equivocal benefits on physical function and activities of daily living.^64,65 Comprehensive geriatric assessment reduces nursing home admission and hospital falls, prevents postoperative delirium and mortality, and improves mobility after hip fracture.³⁹ Medication optimization may reduce emergency department visits.⁶⁶

In nursing home residents, medication optimization reduces falls, mortality, and hospitalization.^54,67 Exercise and Yoga may improve mobility³⁸ and balance.⁴⁰ The benefit of oral nutrition supplementation and vitamin D supplementation is uncertain.^58,65

Frailty Screening in Primary Care and Acute Hospital Settings

Given the availability of validated frailty assessment tools and efficacious interventions proven in randomized controlled trials, a primary care-based integrative care model, encompassing routine frailty screening, comprehensive geriatric assessment for screen-positive patients, and tailored interventions holds potential in preventing and managing frailty. However, a meta-analysis of six randomized controlled trials and two controlled studies conducted in the Netherlands showed that such a model failed to improve functional status, quality of life, and clinical outcomes at one year compared with usual care.⁴⁶ A quality improvement collaborative to identify patients with frailty and perform comprehensive geriatric assessment within the first 72 hours of acute hospital admission in England did not find reductions in length of stay, in-hospital mortality, 30-day readmission, or institutionalization over the 11-month post-implementation period.⁶⁸ These findings contrast with the positive effect of exercise,³⁸ oral nutrition supplementation,^37,63 and comprehensive geriatric assessment^39,47 from clinical trials conducted in carefully selected patients. Possible explanations for the inconsistent findings include differences in candidate selection, standard of care in the comparison group, and fidelity of and adherence to the interventions. The effectiveness of an integrated care model in other health care environments warrants additional research.

Frailty Screening Before Stressful Treatment

The rationale of frailty screening before stressful treatment is to improve candidate selection, proactively optimize risk, and offer person-centered care to improve treatment outcomes. In a cluster randomized controlled trial of 40 oncology practices in the United States, providing oncologists with a summary of domain-specific impairments from comprehensive geriatric assessment and tailored recommendations reduced serious chemotherapy toxicity without compromising treatment efficacy in older patients with cancer.⁴² More patients in the comprehensive geriatric assessment group started less intensive chemotherapy, suggesting that treatment intensity was modified based on the comprehensive geriatric assessment findings. In an Australian multicenter randomized controlled trial, comprehensive geriatric assessment integrated into oncology care of older patients with cancer led to better quality of life and fewer unplanned hospitalizations.⁴³ In a large health care system in the United States, routine preoperative frailty screening, followed by discussion with surgeons about the patient’s frailty and prognosis, palliative care consultation to clarify patients’ goals and expectations, and modification of the treatment plan (e.g., surgical decision and procedural choice), was associated with a reduction in postoperative mortality.⁴⁴ Similar findings were observed when the National Health Service in England introduced a guideline that financially incentivized a geriatrician’s assessment for all older patients admitted with serious injury.⁴⁵ Prehabilitation programs, aimed at optimizing modifiable risk factors for poor surgical outcomes by typically involving exercise, patient education, nutritional supplement, and smoking cessation for 4 weeks, may facilitate functional recovery after orthopedic surgery⁶⁹ and colorectal cancer surgery.⁷⁰ Their effectiveness in patients with frailty or in those undergoing other types of surgery remains uncertain.

EVIDENCE GAPS AND FUTURE DIRECTIONS

Some interventions are beneficial for people who live with frailty, yet the benefit of routine frailty screening followed by tailored interventions has not been consistently demonstrated outside selected clinical settings (e.g., oncology and surgery). Such discrepancy calls for additional research on frailty identification strategies (routine versus targeted), choice of frailty tools, and intervention delivery in routine care. Evidence gaps exist on interventions to prevent or reverse frailty and their cost-effectiveness, standard sets of outcome measures for the evaluation of frailty interventions, and treatment effect heterogeneity by frailty (i.e., how the benefits and harms of a treatment vary by the degree of frailty).⁵ Although unmet needs exist across the care spectrum, given the high stakes and immediacy of consequences, making hospital care safer for older adults with frailty should be seen as a high priority. Geriatric cardiology, geriatric oncology, orthogeriatrics, and their kin may prove workable models for other fields, as long as such approaches are taken as a testable hypothesis and not a fait accompli. Geriatrics employs complex interventions resulting in individualized care plans for people with complex needs. Such approaches merit emulation. In some countries (e.g., France, Canada, and China), community-based screening and management have been initiated. The long-term effectiveness of such effort is yet to be determined. Better understanding of the biology of frailty will aid in the identification of modifiable risk factors⁴ and development of potential therapeutics (e.g., “gero-protectors”¹⁹) for prevention and treatment of frailty.

Given the pressing need, the variation in health care systems, and the costly and time-consuming nature of randomized controlled trials, such trials are often impractical. One innovative strategy to address this challenge is the hybrid effectiveness-implementation study.⁷¹ This study design not only evaluates the effectiveness of an intervention in real-world, local settings but also explores the best ways to implement it. For decision-makers, the advantage lies in the rapid uptake of these interventions, while considering local factors that affect implementation at specific sites. Absent compelling evidence favoring one frailty tool over another, such studies can guide decision-makers in selecting the most appropriate frailty measure. Another strategy is Knowledge Translation, a process where research evidence is assembled and implemented. This involves adapting, evaluating, and advancing the evidence in various clinical settings, as exemplified in how orthogeriatric care has been adopted across trauma centers in England.⁴⁵

CONCLUSIONS

Assessing frailty enables clinicians to understand the variability of health and medical complexity, provide care tailored to the individual’s goals and health needs, and make decisions about stressful treatments based on the person’s vulnerability. Frailty-guided clinical care has the potential to overcome the ineffectiveness of the current models of care by treating older persons holistically, rather than as a fragmented collection of illnesses. To fully realize the benefits of frailty-guided clinical care, additional research is needed to narrow the gaps in our knowledge in measurement, novel treatments, clinical management, and optimal training for clinicians across diverse settings.

KEY CLINICAL POINTS.

• Assessing frailty enables clinicians to predict prognosis and risk of adverse health outcomes; target the delivery of evidence-based interventions; and tailor clinical management, including decisions about stressful treatments.

• Frailty should not be used as a convenient way to withhold potentially effective treatments, rather as a tool to facilitate a patient-centered care.

• Management should aim to increase physiologic reserve to build robustness and resilience and prevent or mitigate stressors.

• The interventions that have proven efficacious in clinical trials (e.g., exercise, nutritional supplementation, comprehensive geriatric assessment) have not consistently shown similar effectiveness in routine care settings, indicating implementation challenges.

• The benefit of routine frailty screening has been demonstrated in high-risk clinical settings (e.g., oncology and surgery); its benefit in primary care settsings remains to be established.