Frailty

Introduction

Elderly persons can become frail. It means weak or unhealthy, or easily damaged, broken or harmed. Frailty refers to a condition in which a person exhibits diminished ability to undertake essential social activities of daily living under minor environmental stressful situations. There is a diminished reserve in the physiological function of different organ-systems of the body to carry out important daily activities and to maintain adequate homeostasis.

In such a background, any minor illness or adverse drug effects lead to disproportionate loss of function, increased risk of disability, and increased risk of death from the effects of a stressor. It must be noted that a similar amount of stress does not cause any disturbance in a physically fit individual of the same age and sex. Thus, frailty is a progressive physiological decline in multiple organ systems marked by loss of function, loss of physiological reserve and increased vulnerability to disease and death.¹ An apparently minor stressor event is associated with adverse outcome.

Frail older patients, unlike robust, are visibly more vulnerable, withdrawn, unsteady and weak and they tend to have more complications as they age and a higher rate of hospitalization.² They exhibit different pathologic states and present clinical manifestations in an atypical manner. Frail elderly individuals are highly susceptible to adverse health outcomes. There is functional decline, decreased mobility, falls, and social withdrawal.³

Frailty is a clinical syndrome associated with increased risk of functional disability, and is a dynamic process. It is common in older adults and in those with multiple co-morbidities. The condition may be encountered independently, thus differing from ageing.⁴

Domains in frailty

Frailty is a complex disorder that occurs during the aging process. The frail person exhibits impaired function in different specific domains (Table 1). Each domain is assessed while making a comprehensive assessment of frailty. These examinations in different domains are necessary before applying the term ‘frail’ to an individual. It must be noted that not all old persons are frail.

The objective criteria for the diagnosis of frailty have been formulated by Linda Fried and her colleagues who proposed a clinical phenotype of frailty as a well defined syndrome with biological underpinnings. They hypothesized that the clinical features of frailty are related in a mutually exacerbating cycle of negative energy balance, sarcopaenia, diminished strength and tolerance for exertion.2 Frailty is defined as a condition having any three of the following five attributes (Table 2).

Frailty is both a physiologic and a biologic syndrome separate from normal aging process and from disability. Ageing is far riskier for people who are frail. The biology of frailty appears to be independent of age and specific disease states.

Frail people may develop functional decline and disability following exposure to a stressor such as an infection (influenza), fall, death of spouse or children, or addition of a new drug in the treatment regimen. These individuals do not possess the resources to respond and maintain adequate homeostasis. The same stresses cause little disturbances in a fit person of the same age. Frailty must be recognized early. The occurrences of acute illnesses and loss of reserve need to be evaluated. An early intervention may help in reversal of some of the aspects of frailty or may delay the onset of disability in elderly.³ As an example, a person with heart failure requires treatment of the basic condition, but also an exercise program to improve musculoskeletal function, balance, aerobic capacity, and nutritional support to restore the lost weight.

Aetiopathology

The development of frailty is influenced by genes, environment and lifestyle. The persons with frailty exhibit an excess loss of functional muscle. There is some deterioration in executive function. Different body systems become dys-regulated on an anatomic, molecular and physiologic level as people reach old age. Some of these systemic changes are more quickly noticeable in people who are frail. The studies have linked frailty to an increase in inflammation and blood clotting activity. There is a decline in humoral and cell-mediated immunity with advancing age. There is over expression of cytokines, decline in the level of hormones, loss of muscle mass and muscle strength or sarcopaenia.

Frail patients exhibit significantly higher serum interleukin (IL)-6 levels and significantly lower levels of haemoglobin and haematocrit values than non-frail patients. Serum IL-6 level is inversely related to haemoglobin and haematocrit in frail group, but not in non-frail group. The subclinical anaemia might be related to chronic inflammatory state as evident by raised levels of IL-6.⁴

Frail patients show increased levels of reactants linked to injury or inflammation such as C-reactive protein (CRP) and clotting factor VIII. Some patients even demonstrate increased levels of the clotting breakdown product-C dimmer.⁵

Frailty is a set of linked physiologic deteriorations with loss of cellular energy production, the key underlying biological process, leading to the altered physiology. The interaction of age-related physiologic deterioration and different disease processes such as anaemia, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), conditions that interfere with muscle function such as diabetes mellitus, peripheral vascular disease, polymyalgia rheumatica, and pain by limiting the capacity to undertake exercise result in the development of frailty.

Sarcopaenia

The persons with frailty exhibit loss of functional muscle. The word sarcopaenia has been derived from the Greek roots sarx- for flesh and penia-for loss. Sarcopaenia is age-related decline of both muscle mass and function that affects ambulation, mobility, nutrient intake and status and functional independence.⁶ Sarcopaenia is a syndrome characterized by progressive and generalized loss of skeletal mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life and death.⁶ The decline in muscle mass and function affects ambulation, mobility, nutrient intake and status and functional independence.⁷

Clinical features

The patient with frailty presents with a variety of vague complaints and narrates them very slowly. The clinical presentation is often atypical and appear quite late. Often there are multiple co-morbid associated conditions. Frail elderly patients exhibit symptoms such as weight loss, weakness, fatigue, slow walking speed, and low physical activity.8 These manifestations interact with each other and lead to a fall in physiologic reserves. Some of these features are related to the loss of muscle mass and muscle strength.

The patients often present with falls and unsteadiness. Many illnesses present with falls, confusion or incontinence rather than more specific signs and symptoms. These individuals often exhibit reduced perception of pain and are febrile.

Clinical assessment

A comprehensive assessment of the patient must be made with a detailed, slowly elicited history, and a thorough physical examination. Frailty may exhibit the following features: 1) weight loss of 4.5 kg or more during past implying poor nutritional status, catabolic metabolism and sarcopaenia, 2) poor endurance presenting with a feeling of exhaustion, 3) weakness as demonstrated by poor grip strength, 4) slow walking with short steps, and 5) decreased physical activity. The cognitive function, gait, balance, hearing capacity and nutrition and ability to perform daily normal tasks are to be assessed. The findings help in planning the regimen to deal with acute problem and to improve overall health and function, with an aim to reduce the likelihood of recurrence of subsequent illness and improve the quality of life. The presence of co-morbidities is to be recognized.

Treatment

No specific treatment for frailty is available. The treatment of elderly persons who are frail involves the treatment of the precipitating acute illness and the underlying loss of function. There is also need to prevent any further loss of functions by early intervention. After treating the precipitating event, a multi-pronged approach in the management is necessary to improve the musculoskeletal function, and balance. Nutritional support is necessary to restore lost weight. Thus, two factors such as physical activity and diet are readily modifiable. Pharmacological intervention can also be undertaken, though the benefits from such interventions are less evident.

Exercise

Exercises are necessary to improve flexibility, strength and balance. Inactivity forms an important factor contributing to the loss of muscle mass and strength. Immobilization induces anabolic resistance, skeletal muscle apoptosis, sarcopaenia and frailty at old age.^{9, 10} Physical exercise strengthens the muscles, reduces levels of inflammatory factors and increases IGF levels to a small degree. Exercise is one of the important factors in therapy that can help in stopping frailty.

Diet

Decreased food intake especially protein leads to weight loss and decreased muscle mass. It aggravates frailty. Often there is anorexia. Loss of muscle mass occurs from an imbalance between protein degradation and synthesis rates. The elderly individuals need an increased dietary protein and amino acid.¹¹ Leucine, an essential amino acid stimulates muscle protein anabolism in healthy elderly adults.¹² In the background of this, administration of proteins rich in leucine is likely to prevent sarcopaenia.13 Adequate food intake, protein supplementation and supplemental creatine, and vitamin D help in maintenance of muscle quality. Creatine supplementation may be beneficial in the management of sarcopaenia.¹⁴

Often the elderly patients exhibit proximal muscle weakness due to vitamin D deficiency. Vitamin D supplementation helps the treatment of sarcopaenia. Calcium and vitamin D are to be given as a prophylaxis for osteoporosis. Administration of 800 IU of vitamin D3 for a period of 2 to 12 months exhibits improvement in lower extremity strength and reduces the risk of all.¹⁵

The underlying diseases such as diabetes mellitus, congestive heart failure, Parkinsonism, osteoarthritis, and anaemia should be treated. The use of ACE inhibitors is associated with an increase in lower extremity lean body mass compared to those who are using other anti-hypertensives.¹³ Loss of strength, and gait disturbances need treatment with analgesics and physiotherapy. Hydration must be maintained. Postural hypotension should be corrected. Medication must be rationalized. Visual disturbances are to be corrected.

Nutrition and physical exercise have been considered as cornerstones in the management of sarcopaenia.¹⁴ A properly supervised exercise program if carried out for a long period of time has beneficial effect. Muscle strength and mass increases by undertaking resistance exercise training. It also improves protein accumulation in skeletal muscles. Aerobic exercise training may help ageing skeletal muscles and improve insulin sensitivity.

Nutritional deficiencies have to be corrected. Caloric intake must be increased to cope with the increased demands from exercise. The intake of protein should be increased. It should be more than 1.2 g per kilogram of body weight per day. Caution must be taken to curtail the intake of protein in presence of renal insufficiency. The protein balance in skeletal muscle will improve with addition of leucine, beta-hydroxy-beta-methybutyrate, creatine and some milk-based proteins. There is need to correct vitamin D deficiency to improve muscle function.

Medication

There is no specific medication for the treatment of sarcopaenia. Attempts are made to inhibit myostatin and manipulation of neuromuscular junction. Anabolic hormones have not shown any beneficial response.

Many disease states lead to frailty that includes diabetes mellitus, and anaemia. Diabetes mellitus is associated with decline in muscle strength. There is an increased rate of falls among frail persons. The level of angiotensin II is elevated in diabetes which stimulates caspase 3 to cleave actomyosin to actin and myosin. Insulin resistance facilitates fat infiltration within the muscle cells. Coexistent neuropathy causes a decrease in motor unit firing that is responsible for the maintenance of muscle quality. Atherosclerosis is responsible for a fall in blood flow to muscle which in turn prevents adequate muscle rejuvenation.¹³ Anaemia should be treated with iron supplementation or with erythropoietin or darbepoietin-alpha in chronic renal failure. Depression is often associated with frailty.

Prevention

There is no specific modality of treatment for frailty. Since multiple pathways are involved in the development of sarcopaenia that has a key role in the development of frailty, the trials have shown that the condition can be prevented by muscle strengthening exercises, healthy diet, adequate amount of sleep, administration of hormones and growth factors, and lifestyle interventions There is a need to reduce the number of drugs taken, to train balance and gait, to correct postural hypotension by rationalizing medication, for adequate hydration and use of non-steroidal anti-inflammatory drugs that cause salt and water retention thereby increasing the circulating volume, and to direct attention to those factors to reduce risk of falls.

Conflict of Interest

Nil