Fraility

by John E. Morley, MB, BCh

(Reprinted with permission)

     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 them. However, when asked to provide the characteristics that make a particular person frail, they are often at a loss. Recently, fried and her colleagues 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:
         1. Unintentional weight loss (10 pounds or more in a year)
         2. Self-reported exhaustion
         3. Weakness as measured by grip strength
         4. Slow walking speed
         5. Low physical activity

     Using this definition, they found that 6.9% of a community-dwelling population was frail. 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 Fried framework allows us to determine the pathophysiology of frailty. It places frailty in an intermediate position between being functional and developing functional impairment and/or comorbidity directly associated with a disease process. We must recognize those physiological factors whose deterioration may be due to environmental stressors or to preprogrammed aging factors. These factors play a central role in the development of frailty. This is troublesome to some geriatricians as has been elucidated by Muriel Gillick of Harvard. Numerous factors play a role in the development of frailty. These include:

          1. Anorexia
          2. Sarcopenia
          3. Immobility (decreased physical activity)
          4. Atherosclerosis
          5. Balance impairment
          6. Depression
          7. Cognitive impairment
      It is now well recognized that older persons develop a physiological anorexia of aging. When they develop dis-ease processes, this results in the onset of chronic under nutrition resulting eventually in fatigue, weakness, cachexia, and micronutrient deficiencies. 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 appear to be key to this accelerated muscle loss. 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. 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 lead to hip fracture, starting a cycle of immobility leading to frailty. Atherosclerosis can lead to frailty by reducing cardiac function resulting in a decline in VO 2 Max. It can also lead to cognitive impairment secondary to small strokes. Atherosclerosis in the lower limbs (i.e., peripheral vascular disease) can result in sarcopenia secondary to nutrient deprivation of the muscles and slowed walking speed due to intermittent claudication. Balance deteriorates over the lifespan. Decreased balance results in falls, leading to 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. Depression leads to a reduction in mobility and a pervasive feeling of fatigue. It also leads to a slowing of thought process. 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. Physical activity often declines in the cognitively impaired, as does food intake. Clearly, there are a number of factors that are amenable to intervention, suggesting 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 which therapies make sense for a frail elderly person and which therapies 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. As such, 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 as illustrated in the poster at the center of this issue of Aging Successfully.