While the pathophysiology of frailty is still being elucidated, its consequences have been well characterized in prospective studies. Four main consequences are important for clinical practice: (1) ineffective or incomplete homeostatic response to stress, (2) multiple coexisting diseases (multi- or comorbidity) and polypharmacy, (3) physical disability, and (4) the so-called geriatric syndromes. We will briefly address each one of these consequences.
Frailty can be considered a progressive loss of reserve in multiple physiologic functions. At an early stage and in the absence of stress, mildly frail older individuals may appear to be normal. However, they have reduced ability to cope with challenges, such as acute diseases, traumas, surgical procedures, or chemotherapy. Acute illness involving a hospital stay is associated with undernutrition and inactivity, which sometimes may be of such magnitude that the residual muscle mass fails to meet the minimal requirement for walking. Even when nutrition is reinstated, energy reserves may be insufficient to adequately rebuild muscle mass. Older persons have a reduced ability to tolerate infections, in part because they are less able than younger people to build a dynamic inflammatory response to vaccination or infectious exposure; thus, infections are more likely to become severe and systemic and to resolve more slowly. In the context of tolerance to stress, assessing aspects of frailty can help estimate the individual’s ability to withstand the rigors of aggressive treatments and to respond to interventions aimed at infection as well as the caregiver’s ability to anticipate and prevent complications of hospitalization and generally to estimate prognosis. Accordingly, treatment plans may be adjusted to improve tolerance and safety; bed rest and hospitalization should be used sparingly; and infections should be prevented, anticipated, and managed assertively.
Comorbidity and Polypharmacy
Older age is associated with high rates of many chronic diseases (Fig. 11-4). Thus, not unexpectedly, the percentage of individuals affected by multiple medical conditions (co- or multimorbidity) also increases with age. In frail older individuals, comorbidity occurs at higher rates than would be expected from the combined probability of the component conditions. It is likely that frailty and comorbidity affect each other, so that multiple diseases contribute to frailty and frailty increases susceptibility to diseases.
Clinically, patients with multiple conditions present unique diagnostic and treatment challenges. Standard diagnostic criteria may not be informative because there are additional confusing signs and symptoms. A classic example is the coexistence of deficiencies in iron and vitamin B12, creating an apparently normocytic anemia. The risk/benefit ratio for many medical and surgical treatment options may be reduced in the face of other diseases. Drug treatment planning is made more complex because comorbid diseases may affect the absorption, volume of distribution, protein binding, and, especially, elimination of many drugs, leading to fluctuation in therapeutic levels and increased risk of under- or overdosing. Drug excretion is affected by renal and hepatic changes with aging that may not be detectable with the usual clinical tests. Formulas for estimating glomerular filtration rate in older patients are available, whereas the estimation of changes in hepatic excretion remains a challenge.
Patients with many diseases are usually prescribed multiple drugs, especially when they are cared for by multiple specialists who do not communicate. The risk of adverse drug reactions, drug–drug interactions, and poor compliance increases geometrically with the number of drugs prescribed and with the severity of frailty. Some general rules to minimize the chances of adverse drug events are as follows: (1) Always ask patients to bring in all medications, including prescription drugs, over-the-counter products, vitamin supplements, and herbal preparations (the “brown bag test”). (2) Screen for unnecessary drugs; those without a clear indication should be discontinued. (3) Simplify the regimen in terms of number of agents and schedules, try to avoid frequent changes, and use single-daily-dose regimens whenever possible. (4) Avoid drugs that are expensive or not covered by insurance whenever possible. (5) Minimize the number of drugs to those that are absolutely essential, and always check for possible interactions. (6) Make sure that the patient or an available caregiver understands the administered regimen, and provide legible written instructions. (7) Schedule periodic medication reviews.
Disability and Impaired Recovery from Acute-Onset Disability
The prevalence of disability in self-care and home management increases steeply with aging and tends to be higher among women than among men (Fig. 11-5). Physical and cognitive function in older persons reflects overall health status and predicts health care utilization, institutionalization, and mortality more accurately than any other known biomedical measure. Thus, assessment of function and disability and prediction of the risk of disability are cornerstones of geriatric medicine. Frailty, regardless of the criteria used for its definition, is a robust and powerful risk factor for disability. Because of this strong relationship, measures of physical function and mobility have been proposed as standard criteria for frailty. However, disability occurs late in the frailty process, after reserve and compensation are exhausted. Early in the development of frailty, body composition changes, reductions in fitness, homeostatic deregulation, and neurodegeneration can begin without affecting daily function. As opposed to disability in younger persons, in which the rule is to look for a clear dominant cause, disability in frail older persons is almost always multifactorial. Multiple disrupted aging processes are usually involved, even when the precipitating cause seems unique. Excess fat mass, poor muscle strength, reduced lean body mass, poor fitness, reduced energy efficiency, poor nutritional intake, low circulating levels of antioxidant micronutrients, high levels of proinflammatory markers, objective signs of neurologic dysfunction, and cognitive impairment all contribute to disability. The multifactorial nature of disability in frail older persons reduces the capacity for compensation and interferes with functional recovery. For example, a small lacunar stroke that causes problems with balance in a young hypertensive individual can be overcome by standing and walking with the feet further apart, a strategy that requires brain adaptation, strong muscles, and a high energy capacity. The same small lacunar stroke may cause catastrophic disability in an older person already affected by neurodegeneration and weakness, who is less able to compensate. As a consequence, interventions aimed at preventing and reducing disability in older persons should have a dual focus on both the precipitating cause and the systems needed for compensation. In the case of the lacunar stroke, interventions to promote mobility function might include stroke prevention, balance rehabilitation, and strength training.
As a rule of thumb, the assessment of contributing causes and the design of intervention strategies for disability in older persons should always consider the four main aging processes that contribute to frailty. One of the most popular approaches to disability measurement is a modification of the International Classification of Impairments, Disabilities and Handicaps (World Health Organization, 1980) proposed by the Institute of Medicine (1992). This classification infers a causal pathway in four steps: pathology (diseases), impairment (the physical manifestation of diseases), functional limitation (global functions such as walking, grasping, climbing stairs), and disability (ability to fulfill social roles in the environment). In practice, the assessment of functional limitation and disability is performed either by (1) self-reported questionnaire concerning the degree of ability to perform basic self-care or more complex ADLs or by (2) performance-based measures of physical function that assess specific domains, such as balance, gait, manual dexterity, coordination, flexibility, and endurance. A concise list of standard tools that can be used to assess physical function in older persons is provided in Table 11-4. In 2001, the WHO officially endorsed a new classification system, the International Classification of Functioning, Disability and Health, known more commonly as the ICF. In the ICF, health measures are classified from bodily, individual, and societal perspectives by means of two lists: a list of body functions and structure and a list of domains of activity and participation. Since an individual’s functioning and disability occur in a context, the ICF also includes a list of environmental factors. A detailed list of codes that allow the classification of body functions, activities, and participation is being developed. The ICF system is widely implemented in Europe and is gaining popularity in the United States. Whatever classification system is used, the health care provider should try to identify factors that can be modified to minimize disability. Many of these factors are discussed in this chapter. Important issues related to aging that are not addressed in this chapter but are covered elsewhere include dementia (Chap. 35) and other cognitive disorders including aphasia, memory loss, and other focal cerebral disorders (Chap. 36).
TABLE 11-4Tools for Functional Assessment in Older Patients ||Download (.pdf) TABLE 11-4Tools for Functional Assessment in Older Patients
|Measurement Instrument ||Evaluation ||Activities/Reference ||Notes |
|Index of independence in ADLs ||Self-reported ||Difficulty/need for help in bathing, dressing, using toilet, transferring, continence, feeding (S Katz et al: JAMA 185:914, 1963) ||Short and simple, but subjective |
|Instrumental ADLs ||Self-reported ||Difficulty using the telephone, using a car/public transportation, shopping, preparing meals, housework, managing medications, financial management (MP Lawton et al: Psychopharmacol Bull 24:609, 1988) ||Short and simple; sex-biased and culturally biased items |
|Functional Independence Measure ||Consensus multidisciplinary team ||Motor (eating, grooming, bathing, dressing, toileting, managing bladder/bowels, transferring, walking, climbing stairs); cognitive (auditory comprehension, verbal expression, social interaction, problem solving, memory) (RA Keith et al: Adv Clin Rehabil 1:6, 1987) ||Administered by trained health professionals |
|Barthel Index ||Professionally evaluated ||Independence and need for help in feeding, transferring from bed to chair and back, grooming, transferring to and from toilet, bathing, walking, climbing stairs, dressing, continence (FI Mahoney et al: Md State Med J 14:61, 1965) ||Administered by trained health professionals |
|Mobility Questionnaire ||Self-reported ||Severe difficulty walking ¼ mile and/or climbing stairs ||Short and simple |
|Short Physical Performance Battery ||Objective performance based ||Time required to walk 4 m, rise from a chair 5 times, maintain balance for 10 sec in the side-by-side, semi-tandem, and tandem positions (JM Guralnik et al: J Gerontol 49:M85, 1994) ||Some training required |
|Berg Balance Scale ||Objective and professionally evaluated ||Performance in 14 tasks related to balance (KO Berg et al: Arch Phys Med Rehabil 73:1073, 1992) ||Typically used by physical therapists |
|Walking speed ||Objective performance ||Measure walking speed over a 4 m course (S Studenski: J Nutr Health Aging 13:878, 2009) ||Simple and powerful, but limited to patients who can walk |
|6-Minute walk ||Objective performance based ||Distance covered in 6 min (GH Guyatt: Can Med Assoc J 132:919, 1985) ||Good measure of fitness, walking capacity/endurance |
|Long-Distance Corridor Walk (400 m) ||Objective performance based ||Time to fast-walk 400 m (AB Newman et al: JAMA 295:2018, 2006) ||More challenging than the 6-min walk |
The term geriatric syndrome encompasses clinical conditions that are frequently encountered in older persons; have a deleterious effect on function and quality of life; have a multifactorial pathophysiology, often involving systems unrelated to the apparent chief symptom; and are manifested by stereotypical clinical presentations. The list of geriatric syndromes includes incontinence, delirium, falls, pressure ulcers, sleep disorders, problems with eating or feeding, pain, and depressed mood. In addition, dementia and physical disability are sometimes considered to be geriatric syndromes. The term syndrome is somewhat misleading in this context since it is most commonly used to describe a pattern of symptoms and signs that have a single underlying cause. The term geriatric syndromes, by contrast, refers to “multifactorial health conditions that occur when the accumulated effects of impairments in multiple systems render an older person vulnerable to situational challenges.” According to this definition, geriatric syndromes reflect the complex interactions between an individual’s vulnerabilities and exposure to stressors or challenges. This definition aligns well with the concept that geriatric syndromes should be considered as phenotypic consequences of frailty and that a limited number of shared risk factors contribute to their etiology. Indeed, in various combinations and frequencies, virtually all geriatric syndromes are characterized by body composition changes, energy gaps, signaling disequilibria, and neurodegeneration. For example, detrusor (bladder) underactivity is a multifactorial geriatric condition that contributes to urinary retention in the frail elderly. It is characterized by detrusor muscle loss, fibrosis, and axonal degeneration. A proinflammatory state and a lack of estrogen signaling cause bladder muscle loss and detrusor underactivity, while a chronic urinary tract infection may cause detrusor hyperactivity; all of these factors may contribute to urinary incontinence.
Because of limited space, only delirium, falls, chronic pain, incontinence, and anorexia are addressed here. Interested readers are referred to textbooks on geriatric medicine for a discussion of other geriatric syndromes.
(See also Chap. 34) Delirium is an acute disorder of disturbed attention that fluctuates with time. It affects 15–55% of hospitalized older patients. Delirium has previously been considered to be transient and reversible and a normal consequence of surgery, chronic disease, or infections in older people. Delirium may be associated with a substantially increased risk for dementia and is an independent risk factor for morbidity, prolonged hospitalization, and death. These associations are particularly strong in the oldest old. Fig. 11-16 shows an algorithm for assessment and management of delirium in hospitalized older patients. The clinical presentation of delirium is heterogeneous, but frequent features are (1) a rapid decline in the level of consciousness, with difficulty focusing, shifting, or sustaining attention; (2) cognitive change (rumbling incoherent speech, memory gaps, disorientation, hallucinations) not explained by dementia; and (3) a medical history suggestive of preexisting cognitive impairment, frailty, and comorbidity. The strongest predisposing factors for delirium are dementia, any other condition associated with chronic or transient neurologic dysfunction (neurologic diseases, dehydration, alcohol consumption, psychoactive drugs), and sensory (visual and hearing) deprivation; these associations suggest that delirium is a condition of brain function susceptibility (neurodegeneration or transient neuronal impairment) that precludes the avoidance of decompensation in the face of a stressful event. Many stressful conditions have been implicated as precipitating factors, including surgery; anesthesia; persistent pain; treatment with opiates, narcotics, or anticholinergics; sleep deprivation, immobilization; hypoxia; malnutrition; and metabolic and electrolyte derangements. Both the occurrence and the severity of delirium can be reduced by anticipatory screening and preventive strategies targeting the precipitating causes. The Confusion Assessment Method is a simple, validated tool for screening in the hospital setting. The three pillars of treatment are (1) immediate identification and treatment of precipitating factors, (2) withdrawal of drugs that may have promoted the onset of delirium, and (3) supportive care, including management of hypoxia, hydration and nutrition, mobilization, and environmental modifications. Whether patients who are cared for in special delirium units have better outcomes than those who are not is still in question. Physical restraints should be avoided because they tend to increase agitation and injury. Whenever possible, drug treatment should be avoided because it may prolong or aggravate delirium in some cases. The treatment of choice is low-dose haloperidol. It remains difficult to reduce delirium in patients with acute illness or other stressful conditions. Interventions based on dietary supplementation or careful use of pain medications and sedatives in pre- and postoperative older patients have been only partially successful.
Algorithm depicting assessment and management of delirium in hospitalized older patients. (Modified from SK Inouye: N Engl J Med 354:1157, 2006.)
Falls and Balance Disorders
Unstable gait and falls are serious concerns in the older adult because they lead not only to injury but also to restricted activity, increased health care utilization, and even death. Like all geriatric syndromes, problems with balance and falls tend to be multifactorial and are strongly connected with the disrupted aging systems that contribute to frailty. Poor muscle strength, neural damage in the basal ganglia and cerebellum, diabetes, and peripheral neuropathy are all recognized risk factors for falls. Therefore, evaluation and management require a structured multisystem approach that spans the entire frailty spectrum and beyond. Accordingly, interventions to prevent or reduce instability and falls usually require a mix of medical, rehabilitative, and environmental modification approaches. Guidelines for the evaluation and management of falls, released by the American Geriatrics Society, recommend asking all older adults about falls and perceived gait instability (Fig. 11-17). Patients with a positive history of multiple falls as well as persons who have sustained one or more injurious falls should undergo an evaluation of gait and balance as well as a targeted history and physical examination to detect sensory, nervous system, brain, cardiovascular, and musculoskeletal contributors. Interventions depend on the factors identified but often include medication adjustment, physical therapy, and home modifications. Meta-analyses of strategies to reduce the risk of falls have found that multifactorial risk assessment and management as well as individually targeted therapeutic exercise are effective. Supplementation with vitamin D at 800 IU daily may also help reduce falls, especially in older persons with low vitamin D levels.
Algorithm depicting assessment and management of falls in older patients. HR, heart rate. (From American Geriatrics Society and British Geriatrics Society: Clinical Practice Guideline for the Prevention of Falls in Older Persons. New York, American Geriatric Society, 2010.)
Pain from multiple sources is the most common symptom reported by older adults in primary care settings and is also common in acute-care, long-term-care, and palliative-care settings. Acute pain and cancer pain are beyond the scope of this chapter. Persistent pain results in restricted activity, depression, sleep disorders, and social isolation and increases the risk of adverse events due to medication. The most common causes of persistent pain are musculoskeletal problems, but neuropathic pain and ischemic pain occur frequently, and multiple concurrent causes are often found. Alterations in mechanical and structural elements of the skeleton commonly lead to secondary problems in other parts of the body, especially soft tissue or myofascial components. A structured history should elicit information about the quality, severity, and temporal patterns of pain. Physical examination should focus on the back and joints, on trigger points and periarticular areas, and on possible evidence of radicular neurologic patterns and peripheral vascular disease. Pharmacologic management should follow standard progressions, as recommended by the World Health Organization (Chap. 18), and adverse effects on the CNS, which are especially likely in this population, must be monitored. For persistent pain, regular analgesic schedules are appropriate and should be combined with nonpharmacologic approaches such as splints, physical exercise, heat, and other modalities. A variety of adjuvant analgesics such as antidepressants and anticonvulsants may be used; again, however, effects on reaction time and alertness may be dose limiting, especially in older persons with cognitive impairment. Joint or soft tissue injections may be helpful. Education of the patient and mutually agreed-upon goal setting are important since pain usually is not fully eliminated but rather is controlled to a tolerable level that maximizes function while minimizing adverse effects.
Urinary incontinence—the involuntary leakage of urine—is highly prevalent among older persons (especially women) and has a profound negative impact on quality of life. Approximately 50% of American women will experience some form of urinary incontinence over a lifetime. Increasing age, white race, childbirth, obesity, and medical comorbidity are all risk factors for urinary incontinence. The three main clinical forms of urinary incontinence are as follows: (1) Stress incontinence is the failure of the sphincteric mechanism to remain closed when there is a sudden increase in intraabdominal pressure, such as a cough or sneeze. In women this condition is due to insufficient strength of the pelvic floor muscles, while in men it is almost exclusively secondary to prostate surgery. (2) Urge incontinence is the loss of urine accompanied by a sudden sensation of need to urinate and inability to control it and is due to detrusor muscle overactivity (lack of inhibition) caused by loss of neurologic control or local irritation. (3) Overflow incontinence is characterized by urinary dribbling, either constantly or for some period after urination. This condition is due to impaired detrusor contractility (due usually to denervation, for example, in diabetes) or bladder outlet obstruction (prostate hypertrophy in men and cystocele in women). Thus, it is not surprising that the pathogenesis of urinary incontinence is connected to the disrupted aging systems that contribute to frailty, body composition changes (atrophy of the bladder and pelvic floor muscle), and neurodegeneration (both central and peripheral nervous systems). Frailty is a strong risk factor for urinary incontinence. Indeed, older women are more likely to have mixed (urge + stress) incontinence than any pure form (Fig. 11-18). In analogy with the other geriatric syndromes, urinary incontinence derives from a predisposing condition superimposed on a stressful precipitating factor. Accordingly, treatment of urinary incontinence should address both. The first line of treatment is bladder training associated with pelvic muscle exercise (Kegel exercises) that sometimes should be associated with electrical stimulation. Women with possible vaginal or uterine prolapse should be referred to a specialist. Urinary tract infections should be investigated and eventually treated. A long list of medications can precipitate urinary incontinence, including diuretics, antidepressants, sedative hypnotics, adrenergic agonists or blockers, anticholinergics, and calcium channel blockers. Whenever possible, these medications should be discontinued. Until recently, it was believed that oral or local estrogen treatment alleviated the symptoms of urinary incontinence in postmenopausal women, but this notion is now controversial. Antimuscarinic drugs such as tolterodine, darifenacin, and fesoterodine are modestly effective for mixed-etiology incontinence, but all of these drugs can affect cognition and so must be used with caution and with monitoring of cognitive status. In some cases, surgical treatment should be considered. Chronic catheterization has many adverse effects and should be limited to chronic urinary retention that cannot be managed in any other way. Bacteriuria always occurs and should be treated only if it is symptomatic. Bacterial communities isolated from the urine of women with urinary incontinence appear to differ with the type of incontinence; this observation suggests that the bladder microbiota may play a role in urinary incontinence. If so, this microbial population would be a potential target for treatment.
Rates of urge, stress, and mixed incontinence, by age group, in a sample of 3552 women.
*Based on a sample of 3553 participants. (From JL Melville et al: Arch Intern Med 165:537, 2005.)
Undernutrition and Anorexia
There is strong evidence that the healthy mammalian life span is greatly affected by changes in the activity of central nutrient-sensing mechanisms, especially those that involve the rapamycin (mTOR) network. Polymorphic variations in the gene that encodes mTOR in humans are associated with longevity; this association suggests that the role of nutrient signaling in healthy aging may be conserved in humans. Normal aging is associated with a decline in food intake that is more marked in men than in women. To some extent, food intake is reduced because energy demand declines as a result of the combination of a lower level of physical activity, a decline in lean body mass, and slowed rates of protein turnover. Other contributors to decreased food intake include losses of taste sensation, reduced stomach compliance, higher circulating levels of cholecystokinin, and, in men, low testosterone levels associated with increased leptin. When food intake decreases to a level below the reduced energy demand, the result is energy malnutrition.
Malnutrition in older persons should be considered a geriatric syndrome because it is the result of intrinsic susceptibility due to aging, complicated by multiple superimposed precipitating causes. Many older individuals tend to consume a monotonous diet that lacks sufficient fresh food, fruits, and vegetables, so that intake of important micronutrients is inadequate. Undernutrition in older people is associated with multiple adverse health consequences, including impaired muscle function, decreased bone mass, immune dysfunction, anemia, reduced cognitive function, poor wound healing, delayed recovery from surgery, and increased risk of falls, disability, and death. Despite these serious potential consequences, undernutrition often remains unrecognized until it is well advanced because weight loss tends to be ignored by both patients and physicians. Muscle wasting is a frequent feature of weight loss and malnutrition that is often associated with loss of subcutaneous fat. The main causes of weight loss are anorexia, cachexia, sarcopenia, malabsorption, hypermetabolism, and dehydration, almost always in various combinations. Many of these causes can be detected and corrected. Cancer accounts for only 10–15% of cases of weight loss and anorexia in older people. Other important causes include a recent move to a long-term-care setting, acute illness (often with inflammation), hospitalization with bed rest for as little as 1–2 days, depression, drugs that cause anorexia and nausea (e.g., digoxin and antibiotics), swallowing problems, oral infections, dental problems, gastrointestinal pathology, thyroid and other hormonal problems, poverty, and isolation, with reduced access to food. Weight loss may also result from dehydration, possibly related to excess sweating, diarrhea, vomiting, or reduced fluid intake. Early identification is paramount and requires careful weight monitoring. Patients or caregivers should be taught to record weight regularly at home, the patient should be weighed at each clinical encounter, and a record of serial weights should be maintained in the medical record. If malnutrition is suspected, formal assessment should begin with a standardized screening instrument such as the Mini Nutritional Assessment, the Malnutrition Universal Screening Tool, or the Simplified Nutritional Appetite Questionnaire. The Mini Nutritional Assessment includes questions on appetite, timing of eating, frequency of meals, and taste. Its sensitivity and specificity are >75% for future weight loss of ≥5% of body weight in older people. Many nutritional supplements are available, and their use should be initiated early to prevent more severe weight loss and its consequences. When an older patient has malnutrition, the diet should be liberalized and dietary restrictions should be lifted as much as possible. Nutritional supplements should be given between meals to avoid interference with food intake at mealtime. Limited evidence supports the use of any pharmacologic intervention to treat weight loss. The two antianorexic drugs most often prescribed in older persons are megesterol and dronabinol. Both can increase weight; however, the gain is mostly fat, not muscle, and both drugs have serious side effects. Dronabinol is an excellent drug for use in the palliative-care setting. There is little evidence that intentional weight loss in overweight older people prolongs life. Weight loss after the age of 70 should probably be limited to persons with extreme obesity and should always be medically supervised.