“Fatigue” or “exhaustion” is a common clinical complaint among older adults. Fatigue is often a symptom of underlying medical or psychiatric illness. Cancer, heart disease, chronic lung disease, hypothyroidism, multiple sclerosis and rheumatoid arthritis are just a few of the many diseases or conditions that may present with fatigue; however, for many older persons, no physiological or psychological explanation is identified, and fatigue becomes a diagnosis or a syndrome with which the elderly must attempt to cope across all activities of daily living. In addition to its direct effects on mood and function, persistent fatigue may also elevate risk for later adverse outcomes. In the absence of overt medical conditions that could explain fatigue, it is likely that multiple factors may play a role in its pathophysiology. Metabolic, muscular, inflammatory, neurological and psychological factors may all contribute to unexplained or idiopathic fatigue. Understanding these factors may lead to identification of subtypes of fatigue, for which specific interventions may be proposed. Furthermore, it is clear that describing fatigue with qualifiers, such as cognitive fatigue or muscular fatigue, can facilitate a better understanding of this broad concept.
Most studies of fatigue prevalence show a female preponderance, with females reporting fatigue 1.2 to 2.3 times more frequently than males. Age is a risk factor for chronic fatigue in some studies. Cognitive impairment, anxiety, inflammation- related chronic conditions (e.g., cancer, rheumatoid arthritis), debilitating symptoms (e.g. dyspnoea) and end of life scenarios can identify special populations of older adults at high risk of fatigue. Depression, disease burden and functional status are likely to interact in the perception and impact of fatigue in later life.
Fatigue can be a symptom of underlying medical disease. Commonly cited conditions include cancer, multiple sclerosis, rheumatoid arthritis, lupus, sleep disorders, HIV/AIDS, depression, heart failure, chronic pain conditions, and following stroke or traumatic brain injury.
Fatigue associated with cancer can present as a disease symptom, as an acute side effect of treatment, or as a persistent symptom after completion of treatment.
Possible causes of cancer- related fatigue include anaemia, physical inactivity/deconditioning, central nervous system toxicity of cancer treatment, altered immune function or cancer- related symptoms themselves.
Multiple sclerosis and other neurological disorders
Fatigue is a major symptom of many neurological disorders of both the central nervous system (e.g., multiple sclerosis, Parkinson’s disease) and peripheral nervous system (e.g., muscular dystrophy).
Depression and sleep disorders
Fatigue is a common complaint among patients with major depression. Fatigue is most strongly associated with deficits in social functioning and work productivity.
Fatigue, depression, and sleep disturbances are intimately connected. Depression may lead to deconditioning and sleep disturbance, which in turn can lead to fatigue. Alternatively, depression and fatigue may feed each other, with both arising from a common third factor.
Fatigue is common in stroke survivors and is separable from post- stroke depression. It is rated as one of the worst residual symptoms in up to half of adult stroke survivors and predicts dependency in activities of daily life (ADLS) and death.
Chronic pain conditions
Chronic pain affects half of community living older adults. Pain associated with osteoarthritis is the leading cause of disability among older adults.
Chronic Fatigue Syndrome (CFS)
Risk factors include female gender, less education, lower social class and income, ethnic minority group membership. Poor sleep can be associated with defined sleep disorders such as restless leg syndrome or sleep state misperception, as well as other entities, such as pain, environmental sensitivity (e.g., noise), mental health problems, and poly pharmacy. Psychiatric disorders are 3-5 times more prevalent in CFS.
It is important to consider the context in which fatigue occurs. For example, environmental, family, social, occupational, and personal factors and stressors may all contribute to an individual’s fatigue.
The population with CFS comprises a small portion of a much larger population of individuals affected by prolonged fatigue. CFS overlaps with several other disorders including fibromyalgia, irritable bowel syndrome, temporomandibular disorder, interstitial cystitis, multiple chemical sensitivity, tension headache, chronic low back pain, chronic pelvic pain and post- concussion syndrome. Each entity tends to fall under the purview of a particular medical specialty. All of these entities encompass varying degrees of fatigue, sleep disorder, pain and disability.
Frailty refers to a clinical syndrome whose hallmark is increased vulnerability to stressors secondary to decreased physiologic reserve. Frail older adults are at high risk for major outcomes, including disability, morbidity, and mortality.
Fatigue has been regarded as an integral part of the phenotype of frailty in older adults.
Self- reported tiredness in daily activities is predictive of onset of disability, walking limitations, use of health and social services, decline in physical activity, and mortality. This is true in both young- old and old- old populations.
Mechanisms and modifiers of fatigue
Multiple biological and psychological factors may contribute to or influence fatigue. Biological mechanisms include changes in skeletal muscle function, cardiovascular impairment, anaemia, dehydration and electrolyte disorders, inflammatory mediators, and nutritional deficiencies. Psychological mediators include depression, pain, positive and negative effect, and interpersonal processes. A few of these factors are considered for further exploration.
Skeletal muscle changes
Skeletal muscle is the single largest organ in the body, comprising 45% of body mass. Skeletal muscle is also a significant reserve of energy, comprised by amino acids stored as protein. Therefore, it is possible that a reduction in skeletal muscle mass could influence the availability of energy, the ability to perform work, and the feeling of fatigue with effort.
Sarcopenia is defined simply as age- associated loss in muscle mass. Sarcopenia begins around the 5th or 6th decade. Factors contributing to diminished muscle mass include malnutrition, anorexia and cachexia in diseased states, deconditioning, low testosterone, and growth hormone.
Loss in strength does not parallel loss in muscle mass – strength declines later than do skeletal muscle mass.
Aerobic capacity represents the rate of oxygen consumption during activity, and is determined predominantly by skeletal muscle function. With aging, the oxygen cost of activities becomes a greater percentage of an individual’s maximum aerobic capacity. Reduced aerobic capacity should translate to reduced spontaneous activity with age.
Mitochondria are the major source of energy production in the body. ATP generated by mitochondria is the biological currency of energy used ultimately to power all metabolic activities. Mitochondrial dysfunction can lead to reduced energy production, which could result in fatigue. In addition, decreased oxidative metabolism in mitochondria leads to increased anaerobic metabolism and lactic acid production. Acidosis in skeletal muscle can be perceived as muscular fatigue.
Exercise leads to increased mitochondrial size and number.
Neuromuscular fatigue has been associated with symptomatic fatigue in certain diseases where fatigue is prominent, such as cancer, multiple sclerosis, amyotrophic lateral sclerosis, and end- stage renal disease.
Dehydration and electrolyte disturbances
Mild Hyponatremia (<135 mmol/L) is the most common electrolyte abnormality in any patient group, whether hospitalized or chronically diseased ambulatory. Incidence increases markedly with age, and is associated with higher mortality.
A hypothetical model of fatigue in aging proposes that psychosocial factors (e.g., stress and depression) plus individual differences (e.g., personality and neuroticism) can lead to fatigue directly or indirectly through inflammation. Both fatigue and inflammation interact with, and potentially modify, disease. “Sickness behavior” is a syndrome of anhedonia, anorexia, fatigue, sleep changes, fever, and exaggerated responses to pain. As such, cumulative environmental and immunological burdens may lead to increased inflammatory mediators and decreased, IGF- 1, which may lead to increased diseases of aging, fatigue, and mortality.
Poor sleep quality, high levels of perceived stress, loneliness, and poorer social and emotional functioning are also common correlates of depression, and their apparent association with fatigue appears to be mediated by depressive symptoms also. This suggests that while multiple factors may mark increased fatigue, depression may function as a ” final common pathway ” through which dispositional stress- reactivity, situational stress, social isolation, and poor sleep operate to induce fatigue.
Fatigue may be best characterized as the absence of energy and the mind- body response to that absence. In order to obtain a comprehensive picture of fatigue, it is essential to explore the interaction of biological (e.g., illness), psychological (e.g., affect), and social factors (positive and negative interactions). Between- persons analysis identify “who” have more fatigue, while within- person analysis overtime show “when” people have more fatigue.
In a study of women with osteoarthritis, rheumatoid arthritis, or fibromyalgia, subjects kept daily diaries that included fatigue ratings throughout the day. Fibromyalgia patients reported the greatest levels and fluctuations of fatigue throughout the day. Physical functioning was predicted by fatigue and pain combined, but not by pain alone. In addition, fatigue was predicted by the presence of negative affect as well as the absence of positive effect, with the effect size of the latter double that of the former.
Compared to non- depressed patients, increased daily fatigue in depressed patients is associated with greater increases in daily pain, greater decline in daily enjoyment of interpersonal events, and greater daily negative effect. Stressful or positive interpersonal events predict daily fatigue, even after accounting for pain, depression, and sleep. Fatigue in rheumatoid arthritis patients with greater social engagement is unaffected by negative interpersonal events. In fibromyalgia or rheumatoid arthritis, positive interpersonal events lead to less fatigue on that day, but paradoxically higher fatigue on the following day.
Interpersonal stress can be imposed acutely in a laboratory setting. Discussing a recent negative interpersonal stressor is associated with increases in heart rate and systolic blood pressure. Greater perceived stressfulness is associated with increased fatigue, while ability to preserve positive affect (emotional well- being) was associated with less fatigue.
Resilience is the natural capacity to recover from stress. In patients with osteoarthritis or fibromyalgia, experimental stress followed by induced positive mood improved joviality in both patients groups; however, stress followed by neutral mood improved joviality in osteoarthritis, but not in fibromyalgia. Therefore, patients with osteoarthritis may have greater resilience.
Exercise: Multiple studies have found that slowly graded exercise therapy improves fatigue in chronic fatigue syndrome with no significant adverse effects.
Pharmacotherapy: Evidence for pharmacologic therapy for fatigue is of poor quality.
Fluoxetine improves mood in chronic fatigue syndrome, but not fatigue.
Dr. A.K.M. Aminul Hoque
Associate Prof. (Medicine)
Dhaka Medical College & Hospital,