Course Authors

John E. Morley, M.D.

During the last three years, Dr. Morley has received grant/research support from Vivus, Merck & Co., Pharmacia, B. Braun McGaw, Bayer Corp and Nestec, Ltd. He has also served on the Speakers' Bureau for LXN, Organon, Ross, Pharmacia, GlaxoSmithKline, Aventis, Searle, Roche, Bristol-Myers Squibb, Novartis, Pratt, B. Braun McGaw, Pfizer and Solvay.

Estimated course time: 1 hour(s).

Albert Einstein College of Medicine – Montefiore Medical Center designates this enduring material activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In support of improving patient care, this activity has been planned and implemented by Albert Einstein College of Medicine-Montefiore Medical Center and InterMDnet. Albert Einstein College of Medicine – Montefiore Medical Center is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

 

Learning Objectives

Upon completion of this Cyberounds^®, you should be able to:

• Define and describe frailty

• Discuss the common factors involved in the pathogenesis of frailty

• List the management strategies to treat frailty.

 

The concept of frailty is one that has proved difficult to define. Most clinicians, and for that matter many of the public, can recognize a frail elderly person when they see one. However, when asked to provide the characteristics that make a particular person frail, they are often at a loss.

Recently, Fried and her colleagues(1) have attempted to provide an occupational definition of frailty. They suggest that if a person has three or more of five factors, they should be considered frail. These factors are:

• Unintentional weight loss (10 pounds or more in a year)
• Self-reported exhaustion
• Weakness as measured by grip strength
• Slow walking speed
• Low physical activity.

Using this definition, they found that 6.9% of a community-dwelling population were frail.(1) The Fried frailty phenotype predicted falls, deteriorating mobility, disability, hospitalization and death. This form of frailty is associated with cardiovascular disease, low education and a low income.

The Pathophysiology of Frailty

With the Fried framework, we are now able to determine the pathophysiology of frailty and recognize those physiological factors whose deterioration due to environmental stressors or to preprogrammed aging factors play a central role in the development of frailty. It is important to note that the Fried definition places frailty in an intermediate position -- between being functional and the development of functional impairment and/or comorbidity directly associated with a disease process. This is troublesome to some geriatricians, as has been elucidated by Muriel Gillick of Harvard,(2) who believes that numerous factors play a role in the development of frailty.(3) These include:

It is now well recognized that older persons develop a physiological anorexia with aging. When they are further afflicted with disease processes, this results in the onset of chronic undernutrition and, eventually, fatigue, weakness, cachexia and micronutrient deficiencies.(4) At a basic biochemical level, testosterone deficiency, excess leptin production and cytokine excess can aggravate this anorexia.

Sarcopenia is defined as an excessive loss of muscle associated with aging. While genetically preprogrammed to some extent, a variety of factors appears to be key to this accelerated loss of muscle mass. They include decreased physical activity, testosterone and growth hormone deficiency, and decreased neuronal endplate input into muscles. Mild cytokine excess appears to also play a role in sarcopenia, whereas severe cytokine excess leads to cachexia.(5)

Immobility can be caused by illnesses such as arthritis, which decreases the ability to move a joint, or by pain limiting mobility. Illness can also result in fatigue. The use of physical restraints has long been an inappropriate method to produce immobility iatrogenically. Osteoporosis can set the stage for hip fracture which initiates a cycle of immobility whose endpoint is frailty.

Atherosclerosis can ultimately produce frailty by reducing cardiac function with a resultant decline in VO₂ max and can also lead to cognitive impairment secondary to small strokes. In the lower limbs, peripheral vascular disease from atherosclerosis can result in sarcopenia secondary to nutrient deprivation of the muscles and slowed walking speed from intermittent claudication.

Balance deteriorates over the lifespan. Decreased balance results in falls, creating a fear of falling and decreased mobility with a worsening of frailty. Animal studies have shown a decline in beta-adrenergic input into the cerebellum. The good news is that animal studies have shown that exercise can lead to a re-growth of dendrites and synaptic processes in the cerebellum. Simple exercises such as those associated with Tai Chi, the ancient Chinese exercise form, can result in a restoration of balance and a decline in falls.(6)

Depression leads to a reduction in mobility and a pervasive feeling of fatigue. Depression also produces a slowing of thought processes. Depressed persons are more likely to develop major illnesses, such as myocardial infarction, and to have poorer outcomes following a major event. Depression is a major cause of anorexia and weight loss in older persons.

Cognitive impairment can lead to a decline in processing time and reaction speed resulting in an increase in falls. Diminished physical activity often occurs in the cognitively impaired as does decreased food intake.

Can We Intervene Medically?

Clearly, there are a number of factors, amenable to intervention, which suggests that frailty is a preventable and reversible condition. As such, frailty becomes an important condition on the road to disability and comorbidity associated with disease. Physicians need to recognize frailty at an early stage and institute appropriate therapies. This will greatly enhance the quality of life of many older persons. In addition, frailty has numerous social consequences. For some frail elders, family and physicians need to modify their expectations of aggressive medical therapies for diseases. Certainly, in frail older persons, a discussion regarding their wishes about an advance directive for health is essential.

While not all frail persons will die within five years, many of those who have a physical illness or an emotional dislocation will. Recognition of what therapies make sense for a frail elderly person and those therapies which are heroic and unlikely to improve quality of life or the dying process are essential. Thanks to the work of Linda Fried and her colleagues, frailty is now a more clearly definable syndrome. Therefore, it is time for clinicians to educate their patients concerning the preventive strategies to slow down the onset of frailty (Table 1).

The pathogenesis of frailty remains a complex of intertwined precipitating factors that lead to a vicious cycle of frailty eventually resulting in functional disability, comorbidity and death (Figure 1).

Management of Frailty

The management of frailty follows from its pathogenesis. Obviously, optimal treatment of any diseases that are causing frailty needs to be undertaken. A Geriatric Depression Scale should be done on all persons with frailty and if they are depressed this should be treated.

Resistance exercise is the cornerstone of the management of frailty. Unless there is a major cardiovascular reason inhibiting exercise, all frail persons should undergo resistance exercise training at least three times per week. They should have their rating of perceived exertion (RPE) used to measure their effort and help design the program (Table 2).(7) If they have either muscle tears or arthritis, they should take either Tylenol^® or a non-steroidal anti-inflammatory agent prior to exercising, as this improves long-term strength gain.

Table 2. Rating of Perceived Exertion (RPE).

All males should have a bioavailable testosterone measured and if it is low, testosterone should be replaced. The use of testosterone in women is controversial. Growth hormone replacement has not been demonstrated to increase strength but does increase muscle mass and produce nitrogen retention.

Persons who are eating poorly should be encouraged to increase their food intake. Caloric supplements between meals may be helpful. Orexigenic agents such as dranabinol (marinol; tetrahydrocannabinol) may increase appetite.

Persons with hyperhomocystinemia should be checked for hypothyroidism. Some of these persons may benefit from folate, vitamin B₁₂ and vitamin B₆ ingestion in pharmacological doses. Peripheral vascular disease should be treated with phosphodiesterase inhibitors and aerobic and resistance exercises.

Early cognitive impairment may respond to cholinesterase inhibitors. Balance exercises need to be included in the therapeutic regimen. These can be done simply by standing on one leg with eyes closed. Usually, an older person needs to hold on to something to maintain balance and prevent falling. Tai Chi, an ancient Chinese exercise form, is also an excellent set of exercises to improve balance and reduce falls.

While there are no intervention studies, persons with cytokine excess may benefit from cytokine reduction. Cytokine excess can be assumed when there is an elevated C-Reactive Protein (CRP). Megestrol acetate (Megace^®) reduces cytokines.(8) It has been shown to produce weight gain in older persons who have excess cytokine production. Megestrol decreases testosterone levels resulting in greater fat than lean body mass. Therefore, it needs to be given with testosterone in men. Other side effects of megestrol are deep vein thrombosis and adrenal insufficiency. Thalidomide also decreases cytokines. It has been used for this purpose in patients with AIDS but not in older persons.