Frailty

Frailty refers to a state of reduced physiological reserve that occurs with age and leads to increasing vulnerability to adverse health outcomes from even minor stressor events. Frailty is more common in women than in men, and frail individuals are at increased risk for long-term disability and death.

In this section, we review the following topics:

• Pathophysiology

• Assessment

• Prevention and Management

• Outcomes Associated with Frailty

Pathophysiology

Frailty is characterized by a diminished ability to respond to stressors. In the diagram below, both the frail individual (red line) and the nonfrail individual (green line) experience an acute loss of function in response to an acute illness, such as pneumonia. For the nonfrail individual, the loss of function is small, followed by rapid recovery and return to prior functional status. However, for the frail individual, the same acute illness causes prolonged recovery and a loss of function. In fact, the frail individual may never return to the same functional status he or she had before the illness.

The exact pathophysiology of frailty is not known but is believed to reflect an interplay among chronic inflammation, impaired immunity, and a diminution in physiological reserve across multiple organ systems (see figure below). These effects go beyond what is expected with aging. The changes with frailty can be subtle and, thus, are often dismissed as a normal part of aging.

Although the prevalence of frailty increases with age, it is not limited to older adults. For instance, multiple studies have shown a higher burden of frailty, regardless of age, in people living with HIV infection, people with hemophilia, and minority populations. Frailty among young adults with chronic inflammatory connective tissue diseases, such as systemic lupus erythematosus, is an emerging area of research.

Assessment

Various methods can be used to measure frailty.

Frailty phenotype is one of the most common frailty assessments. For a patient to be considered to have a frailty phenotype, they must have three of the five following characteristics:

• unintentional weight loss

• self-reported exhaustion

• low physical activity

• slow walking speed

• weakness

This frailty assessment method was based on prospective data from the Cardiovascular Health Study (CHS) of 5210 men and women aged 65 years or older. Compared with individuals who had fewer than three frailty characteristics, those with three or more characteristics had a greater incidence of adverse outcomes at 3- and 5-year follow-up.

Unlike CHS phenotype-based frailty assessment, the Rockwood Frailty Index is based on cumulative health deficits and considers as many as 40 deficits in an individual, including symptoms (e.g., shortness of breath), signs, disabilities (e.g., inability to walk without assistance), and laboratory and radiographic data. This index has been validated in several cohorts. Compared with the categorical phenotype model, the Rockwood Frailty Index quantifies the burden of frailty as a continuous measure.

Study of Osteoporotic Fractures (SOF) Index is a brief tool that allows rapid frailty assessment in clinic and for research purpose. Frailty is defined by the presence of two of the following three criteria:

• 5% weight loss in last year

• inability to rise from a chair five times without use of arms

• a “no” response to the question, "Do you feel full of energy?"

Prevention and Management

Managing frailty requires a multidisciplinary approach, including physicians, nurses, pharmacists, physiotherapists, occupational therapists, nutritionists, and social workers. Close contact with caregivers and review of medication are important in assessing the impact of illness and symptoms. Patient preferences (what “matters most” to them) is critical in caring for this vulnerable population.

No medications have been shown to reverse or prevent frailty. Several approaches to reducing the prevalence of frailty or complications associated with frailty have been investigated. These include:

• Inpatient acute care in hospital units for older adults and outpatient comprehensive geriatric assessment programs

• Exercise, which has important physiological effects on the brain, endocrine, immune, and musculoskeletal systems

  • The Lifestyle Interventions and Independence for Elders (LIFE) trial evaluated the effects of structured, moderate-intensity physical activity to reduce major mobility disability in adults aged 70-89 with physical limitations. After 2.6 years, older adults randomized to the physical activity arm had an improvement in walking speed.

• Diet: data on nutritional assessment in frailty are mixed but suggest a benefit of maintaining a balanced diet with protein, fiber, and appropriate fluid intake

• Recognition and treatment of depression and other psychiatric illness

Outcomes Associated with Frailty

Older adults often are not included in prevention, screening, and therapeutic intervention studies. For instance, multiple primary- and secondary-prevention trials have shown a benefit of statins in reducing cardiovascular events and mortality. Most of those trials either excluded, or included very few, individuals aged >80 years. A prospective cohort study of Physicians’ Health Study participants indicated that the benefit of statins may be diminished in frail older adults. Another study among U.S. veterans aged ≥75 years showed primary prevention of all-cause and cardiovascular mortality with statin use, even among very old participants (age >90 years) and those with dementia.

Similarly, symptomatic aortic stenosis is associated with high mortality. Often, affected patients are unable to undergo surgical aortic valve replacement, given the risks associated with surgery. Transcatheter aortic valve replacement (TAVR) has emerged as an alternative therapy in high-risk patients with aortic stenosis (PARTNER trial). However, in a post hoc analysis of 244 patients, individuals in the frail group were found to have increased mortality and worse outcomes than nonfrail participants. In a subsequent study, preoperative frailty level was associated with lower probability of functional improvement and greater probability of functional decline after TAVR or surgical aortic valve replacement (SAVR).

Numerous studies have shown that frailty is better than chronological age in predicting risk of postoperative complications, length of hospital stay, and discharge to a skilled nursing or assisted-living facility. The Edmonton Frail Scale and modified Hopkins Frailty Assessment score are tools used in assessing frailty perioperatively, with the aim of improving these outcomes.