Presentation of Disease in Old Age

Altered Mental Status

Altered mental status (AMS) may often be the only indicator of a serious underlying disease. Presenting symptoms can include disorientation, decreased or nonsensical verbalization, and somnolence or hyperactivity or a mixture of both. When AMS is of rapid onset, accompanied by disturbed consciousness (especially decreased attention) and is due to a medical condition, it meets the criteria for delirium. Delirium can also be associated with sleep disturbances and hallucinations. Delirium is a common presentation of disease in older adult patients and is the most common complication associated with inpatient hospital admission among older adults. The symptoms of delirium may persist for months and are associated with adverse outcomes.

The differential diagnosis of AMS in older adult patients is very broad and encompasses many systems. The presence of preceding clinical symptoms (e.g., change in urine frequency, color, cloudiness, cough, skin tears or sores), low-grade fever, or leukocytosis may suggest an infectious cause. As noted, because of age-related changes in immunity, older adults may not necessarily exhibit a fever or leukocytosis. The most common infectious causes of delirium include respiratory, urine, and skin infections. Another cause may be iatrogenic secondary to medications.

Estimates have suggested that up to 39% of delirium in older adults is attributable to medications owing to the altered pharmacokinetics and pharmacodynamics, as well as the presence of comorbidities and polypharmacy in this population. Medications with a narrow therapeutic index and/or those that cross the blood-brain barrier are the most common culprits, including anticholinergics and benzodiazepines. A systematic review of prospective studies investigating the association between medications and delirium among patients older than 65 years has suggested a higher risk of delirium with the use of opioids, benzodiazepines, and H1 antihistamines such as diphenhydramine. The association is less with corticosteroids, tricyclic antidepressants (TCAs), and digoxin. It is important to note that although opioid use increases the risk of delirium, untreated pain itself can cause delirium. Another cause of drug-related delirium that is frequently underrecognized is serotonin syndrome, a serious adverse reaction that is a predictable result of serotonin excess. The constellation of signs and symptoms of serotonin syndrome that may include delirium often occurs in temporal association with the recent addition of a serotonergic agent or an increase in the dose of drugs known to have serotonergic activity by blocking serotonin reuptake (e.g., selective serotonin reuptake inhibitors [SSRIs], tramadol, trazodone, chlorpheniramine, dextromethor­phan), augmentation of serotonin release (e.g., codeine, levodopa, monoamine oxidase [MAO] inhibitors), or inhibition of serotonin metabolism (e.g., linezolid). Alcohol intoxication or withdrawal should also be considered. Metabolic disorders include electrolyte imbalances, especially sodium disorders, dehydration, hypoglycemia, and hypoxia. Cardiovascular causes of altered mental status include heart failure and myocardial infarction. CNS causes such as infections (e.g., meningitis, encephalitis), stroke, seizures, and subdural hematomas are less common. Finally, miscellaneous causes of altered mental status in older adults include urinary retention and fecal impaction.

Acute abnormal mental status may also occur in the absence of delirium. For example, psychiatric causes, such as dementia with psychosis, psychotic depression, and bipolar disorder, may present with changes in mental status. Psychosis may be accompanied by delusions and hallucinations and is one of the most common noncognitive symptoms associated with Alzheimer dementia. The second most common cause of psychosis in older adults is depression. Mania, although less common in older adults, is characterized by hyperactivity, but patients generally remain oriented.

When patients' mental status is too altered for them to give a reliable history, clinicians must obtain additional information about the history of present illness from family members, friends, caregivers, or health care workers for patients who live in institutional settings. It is also important to review medications with a focus on recent changes and over-the-counter (OTC) medications that may have anticholinergic properties (e.g., those containing diphenhydramine). For the most part, infection and other major medical causes can be identified with a set of simple laboratory studies, including a complete blood cell count with differential, comprehensive metabolic panel, urinalysis, chest x-ray, electrocardiography and, depending the on patient's clinical status, cardiac enzyme levels.

If an infectious cause is suspected but no clear source can be found, a lumbar puncture may be warranted, although a retrospective analysis of 232 hospitalized patients with fever and altered mental status demonstrated that lumbar punctures for suspected nosocomial meningitis in nonsurgical patients have a low yield. Although AMS is unusual in meningitis, it may be a sign of other CNS infection, particularly meningoencephalitis. Furthermore, older patients may not mount the typical immune response associated with these infections, such as fever or leukocytosis. Brain imaging is of value in ruling out stroke or subdural hematoma if there is clinical suspicion of either diagnosis or if the evaluation of AMS is otherwise unrevealing. Recent studies have shown that the routine use of head imaging in the evaluation of older patients with AMS following cardiac surgery and total hip arthroplasty is rarely useful in the absence of focal neurologic deficits. Finally, electroencephalography (EEG) is helpful in diagnosing occult seizures and sometime to distinguish delirium from psychosis.

Weight Loss

Undernutrition is indicated by unintentional weight loss of more than 5% within a year. Unintentional weight loss occurs in up to 15% of community-dwelling older persons, between 20% to 65% of hospitalized patients, and 5% to 85% of institutionalized older persons. Unintentional weight loss is often a marker of severity of comorbidities or undiagnosed disease and may be divided into three causes—social, psychological, and medical.

Social reasons include poverty, functional impairment, social isolation, poor nutritional knowledge, and elder abuse. Most surveys have shown that poverty is the single most important social cause of weight loss. Dependence in activities of daily living (ADLs) and instrumental activities of daily living (IADLs), such as needing assistance with feeding, shopping, or food preparation, are also important factors.

Psychological reasons include psychiatric problems such as depression, paranoia, and bereavement. Depression has been shown to be the major cause of weight loss in the outpatient setting. Of older adults with depression, 90% have weight loss compared to 60% of younger adults with that diagnosis. Depression is also an important cause of weight loss in institutionalized patients.

Medical reasons include dementia, pulmonary and cardiac diseases, malignancy, medications, alcoholism, infectious diseases, poor dentition, endocrine abnormalities, especially hyperthyroidism and diabetes, malabsorption, and dysphagia.

The first step in determining the cause is to assess whether patients have adequate dietary intake. If they have inadequate nutrition, medical and psychosocial factors should be investigated. Medical factors include nausea, constipation, poor oral health, and/or health problems that lead to functional dependence. Medication side effects may also be contributory factors. For example, opioids and anticholinergics may cause constipation, which in turn may cause bloating and poor appetite. Psychosocial factors, including poverty, dementia, depression, and social isolation, should be investigated. The use of geriatric assessment tools such as the Mini-Cog, Mini Mental State Examination (MMSE), or Montreal Cognitive Assessment (MOCA) to screen for cognitive impairment, and the Patient Health Questionnaire-9 (PHQ-9) to screen for depression can help elucidate the cause.

On the other hand, if patients have adequate dietary intake, a search must be undertaken for underlying disease by careful history and physical examination, with special attention paid to symptoms that may suggest malignancy (e.g., cough, constipation, gastrointestinal bleeding), or cardiac, pulmonary, inflammatory bowel, or rheumatic disease. The physical examination should evaluate for lymphadenopathy, palpable masses, and breast or thyroid abnormalities. Initial laboratory testing should include complete blood cell count with differential, comprehensive metabolic panel, determination of levels of prealbumin, albumin, thyroid-stimulating hormone (TSH), and lactate dehydrogenase (LDH), urinalysis, erythrocyte sedimentation rate (ESR), and chest x-ray. Because of its shorter half-life compared to albumin, the prealbumin level is a better indicator of the more acute changes in nutritional state that occur in the inpatient setting. Depending on the patient's clinical findings and preliminary laboratory results, further evaluation may be necessary to determine the cause of the weight loss. However, when investigating potential causes, it is important to keep in mind that weight loss in older adults may not have a disease-based cause but may occur as a consequence of aging and frailty from the so-called physiologic anorexia of the aging and age-related sarcopenia. However, this is often a diagnosis of exclusion.

Fatigue

Fatigue can be defined as tiredness or decreased energy, but excessive daytime fatigue is not a normal process of aging. As the body protects its functional reserve, fatigue may be associated with generalized weakness. Fatigue may be acute or chronic, the latter of which is the result of physical and/or psychological factors. Physiologic causes of fatigue by body systems include hematologic and oncologic (e.g., anemia, cancer, cancer-related therapy), cardiac (e.g., congestive heart failure), renal or liver disease, endocrine (thyroid disease, diabetes), and pulmonary (sleep-related breathing disorders, severe obstructive or restrictive lung diseases).

Fatigue is one of the most common side effects of cancer treatment, with 70% of cancer patients receiving radiation and chemotherapy experiencing this symptom, and that may also persist for years after treatment. Fatigue is also the most common symptom of congestive heart failure (CHF) and is the initial presenting complaint in 10% to 20% of new CHF diagnoses. Obstructive sleep apnea (OSA) is common in patients older than 60 years, with a reported prevalence of 37.5% to 62%; daytime sleepiness is a prominent symptom. Other sleep disorders, such as insomnia or disturbances in sleep-wake cycles that may occur with dementia, can also lead to daytime fatigue. Some chronic infections, such as subacute endocarditis, may also present with fatigue as a chief complaint. Medications are also a common culprit of fatigue in older adults ( Table 33-2 ), particularly antihistamines, anticholinergic medications, sedatives or nonsedating hypnotics, and antihypertensive medications (especially β-blockers at high doses). Finally, psychiatric illnesses, most commonly depression, can cause excessive fatigue.

The evaluation of fatigue begins with a history, with a focus on any symptoms of concern for malignancy (e.g., weight loss) or other body system diseases that may suggest a cause (e.g., dyspnea suggesting anemia, CHF, ischemia, or pulmonary disease, recent bereavement suggesting depression). Geriatric assessment tools such as the PHQ-9 or Geriatric Depression Scale (GDS) can be performed to screen for depression. The Mini-Cog, MOCA, or MMSE can be used to screen for cognitive impairment. Similarly, the physical examination should focus on any red flags (e.g., weight loss suggesting malignancy, edema suggesting CHF).

Fatigue is a frequent side effect of many medications that older adults commonly use. A careful review of medications, including OTC drugs and a temporal association between the onset of fatigue and the addition or dose increase of a medication known to cause fatigue may be simple and helpful step in identifying the cause of the symptom. The list of pharmacologic agents that can cause fatigue is long. Drugs cause fatigue by various mechanisms, most of which are through CNS depression by decreasing excitatory CNS activity or increasing inhibitory CNS activity. A number of drugs used by older adults (e.g., anticonvulsants, antipsychotics, antimicrobials, chemotherapeutic agents, medications used to treat rheumatoid arthritis) cause hematologic toxicity resulting in symptomatic anemia. Other drugs cause fatigue by unknown mechanisms.

Laboratory and diagnostic testing in the evaluation of fatigue must be tailored toward identifying potential causes after obtaining a thorough history and physical examination. Basic laboratory tests (e.g., complete blood cell count, comprehensive metabolic panel, TSH, urinalysis) may be helpful; additional diagnostic tests may be carried out based on history and physical findings (e.g., electrocardiography, echocardiography, brain natriuretic peptide [BNP] level) may be ordered in someone suspected of having CHF; an overnight sleep study might be ordered if obstructed sleep apnea is suspected.

Dizziness

Dizziness is prevalent among older adults in the community and is the presenting complaint of up to 7% of older patients in the primary care setting. Although common, dizziness is not a normal process of aging and can be a vexing clinical problem to diagnose and treat. Dizziness in most older adults has a benign cause but dizziness may also be indicative of a more serious underlying medical condition. One study of patients older than 60 years having dizziness found that 28% had a cardiovascular diagnosis and 14% had a central neurologic disorder. Of note, 22% had no attributable cause of the symptoms identified. Psychological disorders are rare as the primary cause of dizziness, but may be contributing or modulating factors in older adults with dizziness. Furthermore, patients with dizziness may develop a fear of falling, falls, and subsequent disability in daily activities secondary to their symptoms.

To determine the cause of dizziness, it is important first to determine the nature of the presenting symptoms. Dizziness can be classified into four symptom categories—vertigo, presyncope, dysequilibrium, and nonspecific dizziness :

• 1.

  Vertigo is defined as a feeling that one's surroundings are moving and can be episodic or continuous. Causes of vertigo include benign paroxysmal positional vertigo, acute labyrinthitis, Menière disease, vertebrobasilar insufficiency, brain stem stroke, tumors, and cervical vertigo.

• 2.

  Presyncope is defined as a lightheaded feeling or impending faint. It is commonly due to orthostatic hypotension, vasovagal attacks, and decreased cardiac output, such as significant valvular lesions or arrhythmias.

• 3.

  Dysequilibrium is defined as a sense of unsteadiness or imbalance where a person feels as if he or she is going to fall and is usually constant, occurring primarily while standing. It is generally the result of vestibular loss (e.g., acoustic neuroma), proprioceptive (e.g., spinal stenosis) or somatosensory loss (e.g., peripheral neuropathy), a cerebellar or motor lesion (e.g., subcortical or cerebellar infarct, tumor), or multiple neurosensory impairments, such as those occurring in Parkinson disease.

• 4.

  Finally, some nonspecific dizziness symptoms do not fit into any of these categories. They may be described as mild lightheadedness but also may be difficult for patients to describe. Infections (e.g., urinary tract infections), anxiety, or hyperventilation are commonly responsible for nonspecific dizziness.

The evaluation of the differential diagnosis begins with a history and physical examination, with a focus on the nature of the patient's symptomatology. A dizziness simulation battery can be performed to delineate further the type of dizziness from which the patient suffers. For example, reproduction of symptoms with nystagmus in response to the Barany or Dix-Hallpike maneuver is diagnostic for vertigo. Further vestibular concerns can be evaluated with audiometry, brain magnetic resonance imaging (MRI), and/or referral to an otolaryngologist. Presyncope should be evaluated with screening laboratory tests, including a complete blood cell count, comprehensive metabolic panel, urinalysis and thyroid function, electrocardiography, and possible further cardiac studies (e.g., event monitoring, echocardiography) or neurologic testing (e.g., carotid ultrasound, brain MRI), depending on clinical presentation and history. In addition, dysequilibrium may require a neurology evaluation and further neurologic testing.

Falls

Over one third of community-dwelling persons older than 65 years fall each year, and more than 50% of these patients have recurrent falls. Falls are responsible for two thirds of accidental deaths, which are the fifth leading cause of death in older adults. In addition, 20% to 30% of those who fall suffer moderate to severe injuries such as lacerations, hip fractures, or head trauma. Falls are also independently associated with functional and mobility decline. All patients older than 65 years should be screened for a history of falling in the last year because patients who have fallen in the last year are at higher risk for falling again.

Although the cause of most falls is multifactorial in nature, it is useful to understand the separate entities that may be contributing factors or may independently cause falls. These include the following physiologic contributors: cardiac disease (e.g., orthostatic hypotension, arrhythmia, valvular lesions, ischemia); neurologic disease (e.g., stroke, Parkinson disease, subdural hematomas in recurrent fallers, peripheral neuropathy; cognitive impairment); musculoskeletal disorders (e.g., osteoarthritis, leg asymmetry, muscle weakness); sensory impairment (visual and hearing impairment); iatrogenic factors (e.g., medications, physical restraints in institutionalized settings); and primary gait and balance impairments. There are also several other nonphysiologic factors that may cause or contribute to falls, including incorrect use of walking aids, environmental hazards (e.g., loose carpets), performing several activities simultaneously, inappropriate footwear, and hazardous behavior.

If a patient has fallen in the last year, a multifactorial evaluation of the cause(s) should be undertaken. This begins with a history to determine the circumstances surrounding the falls (e.g., loss of balance, tripping secondary to poor vision, presyncopal symptoms). A review should be performed of prescription and nonprescription medications that may be contributing to falls (e.g., sedatives, anticholinergics, nonsedating hypnotics). The physical examination should include orthostatic vital signs, visual acuity testing, and a gait and balance evaluation. The physician can most efficiently observe a patient's gait while the patient is entering and leaving the examination room. Simple tests of balance include observing the patient's ability to stand side by side, semitandem, and full tandem for 10 seconds each and stability during a 360-degree turn. The neurologic examination should evaluate for any focal or generalized weakness, impaired cognition, signs of parkinsonism (e.g., rigidity, tremor), and/or poor proprioception. For patients who are found to have cognitive impairment or focal weakness, further evaluation may include brain imaging to assess for vascular disease. In addition, patients with focal weakness may require musculoskeletal imaging (e.g., to evaluate for osteoarthritis, spinal stenosis, mass lesions) and electromyographic studies to evaluate for possible peripheral neuropathy. The cardiovascular examination should include evaluation for valvular lesions, arrhythmias, and carotid lesions. An electrocardiogram should be obtained, with further cardiac testing if patients have presyncopal or syncopal symptoms (see earlier, “ Dizziness ”). The musculoskeletal examination should focus on any muscle weakness or atrophy, joint abnormalities, foot deformities, or leg asymmetry.

Fever

Fever is the prototypical sign of many infections (most commonly—urinary tract, infections, pneumonias, skin, and intraabdominal infections; less commonly—endocarditis and osteomyelitis), and some malignancies (e.g., lymphoma, renal cell carcinoma, hepatic cell carcinoma) and rheumatologic diseases (e.g., calcium pyrophosphate dihydrate deposition disease, rheumatoid arthritis, temporal arteritis, adult-onset Still disease). Other less common causes include drug reactions, hematomas, and thyroid storm.

The presence of fever serves as a warning sign for potentially life-threatening diseases. However, as noted, the febrile response may be absent in infected older patients. Although errors in measurement may account for some of this variability, older patients, on average, have a lower basal temperature than younger persons. To compensate for this, some have suggested that the use of change from basal temperature might be more sensitive for the presence of infection than absolute temperature. In older adults, an oral temperature higher than 99° F should be considered elevated. One study examined the importance of fever in 470 consecutive older patients who were seen in an emergency room with a temperature of 100.0° F or higher. Three quarters of these patients were classified by the authors as seriously ill.

The fever workup should begin with a history focusing on evaluation for infection, malignancy, or rheumatologic disease. The physical examination should pay attention to the cardiac (e.g., murmurs suspicious for endocarditis) and pulmonary examination (e.g., rales or rhonchi indicating possible pneumonia), lymphadenopathy, skin findings, joint abnormalities, and gastrointestinal examination (e.g., pain, organomegaly or other masses). The laboratory evaluation should begin with a complete blood cell count with differential, urinalysis, urine culture, chest x-ray, and ESR or C-reactive protein (CRP). The last two tests should be done if there is clinical suspicion for osteomyelitis, endocarditis, temporal arteritis/polymyalgia rheumatica, or lymphoma. Further imaging may be warranted if there is clinical suspicion for occult disease, such as intraabdominal abscesses or neoplasm.