Definitions of frailty

Frailty can be intuitively defined as the characteristics of an individual who is thin and weak. Vulnerability, fragility, and lack of resilience are also generally considered characteristics of frail individuals. A broad definition of frailty, developed by Buchner and coworkers in the Seattle arm of the Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) study, states that frailty is any loss of physiologic reserves that predicts or increases the susceptibility to disability. These reserves include relative strength, bone density, and aerobic capacity, and might also include cognitive abilities, motor skills, linguistic ability, various types of memory, visual acuity, and hearing acuity. When young people become temporarily incapacitated from illness or injury, they lose some muscle mass, strength, and aerobic capacity. However, they have enough in reserve that they can recover from the illness or injury using what strength remains to return to preillness levels. If older individuals have lived sedentary lives, they will have gradually lost so much strength that they have little or no reserves; illness or injury will weaken them and they will not have the ability to recover completely. Many families report that grandparents are never the same after the flu or a fall; their reserves, which were once abundant, are gone.

Because frailty can exist before it is obvious, and because it is such a central problem with aging, considerable effort has been expended to clearly define the concept. Using factor analysis, Speechley and Tinetti identified nine variables that loaded heavily on a construct called frailty. Those variables were divided into three subgroups: (1) predictors of future loss of physiologic reserve (eg, age >80 years, depression, sedative use, sedentary lifestyle), (2) indicators of current loss (eg, decreased muscle strength in shoulder or knee, visual loss), and (3) clinical measures of disability (eg, measurements of gait, balance, and lower extremity disability). The frailty syndrome has also been elucidated by Fried, Bandeen-Roche, and coworkers , who characterize frailty as a medical syndrome caused by aggregate declines in multiple molecular, cellular, and physiologic systems, and is indicated by weight loss, exhaustion, low energy expenditure, weakness, and slowness. In proportional hazards models, frail women had a higher risk for losing the ability to perform activities of daily living (ADLs) or instrumental ADLs (IADLs), and a greater risk for institutionalization and death, independent of multiple potentially confounding factors.

Sarcopenia

Sarcopenia , the loss of muscle mass and strength that occurs with aging, is a term coined by Rosenberg in 1988 to describe one of the most noticeable changes that occurs in older women. It has generally been considered a normal part of aging and does not seem to require the presence of disease . However, because most data are cross-sectional, and the speed and degree of loss varies greatly among individuals, defining the limits of “normal” is an ongoing process. Consequently, discussion is ongoing about how much loss of muscle mass is an inevitable part of aging, and how much is caused by disuse . Numerous studies of older athletes have found that for those who have maintained an active lifestyle, the loss of muscle mass is much less than would be predicted by age .

Muscle mass is also lost after illness or surgery. Each day of bed rest results in an estimated 1% loss of muscle strength , and an estimated 75% of hip fracture patients will lose so much muscle mass that they will never regain previous levels of function .

Clearly a link exists between muscle loss and disability. Janssen and colleagues , developed a scale of muscle loss with certain cut points below which odds for disability significantly increased. Encouragingly, even very frail nursing home residents in their 70s, 80s, and 90s can improve muscle strength by as much as 100% through resistance training, resulting in improvement in gait velocity and stair-climbing ability .

Because production of hormones, such as growth hormone, testosterone, and estrogen, are known to be related to strength and diminish with age, treatment of muscle loss with hormones has been investigated. Studies suggest that although some improvements can be attributed to growth hormone, the unwanted side effects are numerous and the improvements minimal . Testosterone replacement therapy is considered a possible treatment of frailty for older men. Although some experts suggest that this treatment might have beneficial effects on muscle mass and strength, determining whether adverse side effects counterbalance any possible benefits is impossible. Despite the fact that testosterone levels in women are also linked to muscle mass and strength and that testosterone production diminishes with age in women, few studies have examined testosterone replacement for older women as a treatment of loss of muscle mass, and none has shown unequivocal improvement in health-related outcomes . Although hormone replacement therapies have been used to try to reverse sarcopenia, strength training is the preferred treatment of age-related muscle wasting .

Sarcopenia

Sarcopenia , the loss of muscle mass and strength that occurs with aging, is a term coined by Rosenberg in 1988 to describe one of the most noticeable changes that occurs in older women. It has generally been considered a normal part of aging and does not seem to require the presence of disease . However, because most data are cross-sectional, and the speed and degree of loss varies greatly among individuals, defining the limits of “normal” is an ongoing process. Consequently, discussion is ongoing about how much loss of muscle mass is an inevitable part of aging, and how much is caused by disuse . Numerous studies of older athletes have found that for those who have maintained an active lifestyle, the loss of muscle mass is much less than would be predicted by age .

Muscle mass is also lost after illness or surgery. Each day of bed rest results in an estimated 1% loss of muscle strength , and an estimated 75% of hip fracture patients will lose so much muscle mass that they will never regain previous levels of function .

Clearly a link exists between muscle loss and disability. Janssen and colleagues , developed a scale of muscle loss with certain cut points below which odds for disability significantly increased. Encouragingly, even very frail nursing home residents in their 70s, 80s, and 90s can improve muscle strength by as much as 100% through resistance training, resulting in improvement in gait velocity and stair-climbing ability .

Because production of hormones, such as growth hormone, testosterone, and estrogen, are known to be related to strength and diminish with age, treatment of muscle loss with hormones has been investigated. Studies suggest that although some improvements can be attributed to growth hormone, the unwanted side effects are numerous and the improvements minimal . Testosterone replacement therapy is considered a possible treatment of frailty for older men. Although some experts suggest that this treatment might have beneficial effects on muscle mass and strength, determining whether adverse side effects counterbalance any possible benefits is impossible. Despite the fact that testosterone levels in women are also linked to muscle mass and strength and that testosterone production diminishes with age in women, few studies have examined testosterone replacement for older women as a treatment of loss of muscle mass, and none has shown unequivocal improvement in health-related outcomes . Although hormone replacement therapies have been used to try to reverse sarcopenia, strength training is the preferred treatment of age-related muscle wasting .

Nutrition

Aging is associated with altered sensations of thirst, hunger, sense of smell, and satiety . When older people have no obvious reason to eat, the frequent result is diets lacking in the variety necessary to provide adequate nutrition. Older women may be at higher risk for micronutrient malnutrition because of difficulty with shopping and meal preparation and simple disinclination to prepare complex meals when the meal will be eaten alone (among women aged ≥75 years, 51% live alone ). Not unreasonably, older persons tend to adapt their diets to individual functional difficulties, such as chewing, self-feeding, shopping for basic necessities, carrying a shopping bag, cooking a warm meal, or using fingers to grasp or handle. These problems can lead to monotonous food consumption and, as a consequence, inadequate nutrient intake. Reporting difficulties in three or more nutrition-related activities has been shown to significantly increase the risk for inadequate intake of energy . Bartali and colleagues found evidence that low intakes of energy and selected nutrients are independently associated with frailty. Semba and colleagues found that low serum micronutrient (various vitamins and minerals) concentrations are an independent risk factor for frailty among disabled older women, and that the risk for frailty increases with the number of micronutrient deficiencies.

Individuals do not need to be thin to be malnourished. In a study examining the nutritional status of rural, homebound elderly, virtually all were deficient in recommended nutrients, but only 5% of those interviewed were underweight (body mass index [BMI] <18.5). In fact, 22% were overweight (BMI 25.0–29.9) and 33% were obese (BMI >30.0) . Overweight and obese older women, particularly those living alone, may be at greater nutritional risk than men who have a high BMI .

Experts have suggested that, although older people’s caloric needs may diminish with age, their need for protein may not, and the current recommended dietary allowance of 0.8 g per kilogram of weight per day is probably insufficient to meet the needs of most older people .

Inadequate diet, and especially inadequate protein, results in low energy, which leads to reduced activity and therefore loss of muscle mass and aerobic capacity, which then diminishes appetite. This vicious circle is further exacerbated by the fact that poor diet, inadequate activity, and (often) inadequate intake of water contribute to constipation, which also diminishes appetite and discourages physical activity ( Fig. 1 ).

The Vicious Circle of Frailty links poor diet and hydration, reduced energy and physical activity, and sarcopenia.

Some suggest that aerobic activity can improve the absorption of nutrients in malnourished older individuals, and resistance training seems to effectively lower dietary protein needs by improving the efficiency of protein absorption . Some studies have suggested that supplementation with essential amino acids can help offset the muscle wasting produced by prolonged bed rest , but no evidence exists that it is a useful way to maintain muscle mass in community-living elders. A study investigating nutritional supplementation and strength training in frail nursing home residents found that nutritional supplementation alone had no effect on muscle mass, and that the supplementation was related to diminished caloric intake in those who did not participate in resistance training. The resistance training had a significant positive effect on strength, gait speed, and overall physical activity . Evans stated that resistance training seems to have the greatest potential for stopping or reversing sarcopenia in malnourished older individuals. This article’s authors would add that it should be combined with proper diet and aerobic exercise.

Clearly, educating older women, and the general population, about the importance of eating adequate amounts of fruits, vegetables, and protein is essential. Proper diet must be combined with enough exercise to stimulate appetite and elimination and maintain enough muscle mass to enable individuals to continue performing (at least) ADLs.

Obesity

An obese individual rarely comes to mind when thinking of a frail person, but in fact the two are not mutually exclusive, and are actually closely linked. By the time an obese woman reaches 80 years of age, she will almost certainly evince the symptoms listed by Speechley, Tinetti, Fried, and Bandeen-Roche of sedentary lifestyle, weakness, exhaustion, low energy expenditure, slowness, difficulty with gait and balance, and lower extremity disability. Obesity as a factor is further elucidated in the following section on relative strength.

Relative strength

As Buchner and deLateur pointed out, an intuitive understanding exists that strength and ability to function are closely interrelated. They were the first to understand that, in terms of function, the key is not absolute strength, but strength relative to height and weight. A woman may be able to leg press 100 lb, but if she weighs 300 lb, she will not be able to stand up. This relationship has recently been corroborated in a longitudinal study that found that sarcopenic obesity , or low muscle mass in relation to fat mass, predicted onset of IADL disability in community-dwelling elders who had no disability . Those who did not develop subsequent disability had significantly higher activity levels than those who developed disabilities, whether obese or not.

Inflammatory markers

Indicators of frailty can be found among blood tests. Low Insulin-like growth factor-1 (IGF-1) levels have been shown to be associated with markers of frailty, especially inflammatory markers, such as interleukin 6 (IL-6) . This finding might partially explain the effectiveness of low-dose aspirin in the prevention of heart attacks. That is, not only does the acetylsalicylic acid decrease the tendency of platelets to aggregate, it also has an anti-inflammatory effect. High levels of cytokines, particularly IL-6, are often observed in elderly people and can apparently accelerate sarcopenia, because IL-6 inhibits the production of IGF-1, an important anabolic stimulus for muscle growth .

The apparent interaction between elevated inflammatory markers and reductions in growth factor signals may be a root cause of progressive muscle wasting . Cappola and colleagues found that older women who had the lowest levels of IGF-1 and high levels of IL-6 showed the greatest decrements in walking performance and functional ability, and increased mortality.

Therapies directed toward inflammatory factors have been available for many years, but their efficacy in treating muscle wasting is either questionable or has not been tested . Reducing the blood levels of IL-6 has not been shown to be as effective in preventing frailty as has, for example, lowering total and low-density lipoprotein cholesterol in preventing coronary artery disease. More likely, correcting frailty causes reduction in the levels of IL-6 and C-reactive protein.

Although a common assumption is that age is the underlying cause of increased inflammatory markers, evidence shows that it may be related to inactivity. McFarlin and colleagues investigated the relationship among age, physical activity, and biomarkers of inflammation. The findings of that study supported previous reports, which inferred that acute exercise or a physically active lifestyle may possess anti-inflammatory properties.