Cognition may be altered by neurodegenerative, vascular, traumatic, anoxic, infectious, and toxic pathophysiological processes. Treating pain in such patients poses challenges, because memory loss, language and speech deficits, and altered levels of consciousness may impair patient ability to communicate meaningful discomfort.¹ Patients with cognitive deficits are less likely to ask for and to receive analgesia, and they may be predisposed to exacerbations of mental and behavioral aberrance given standard analgesic regimens.^1–5

Cognitive impairment, being difficult to measure and lacking definitive diagnostic criteria, has been reported at varying rates in several epidemiological studies.^{6–12,19–24} Published prevalence rates span from 2% to 20%. The most descriptive population-based studies have estimated the prevalence in persons 70 or older to be between 14% and 18%.^6–11 Estimates for incidence rates differ similarly. Elderly populations between the ages of 65 to 75 years have been reported to have incidence rates of 14 to 111 per 1,000 persons in a given year.^11–18 The Mayo Clinic Study of Aging reported 5% to 6% incidence rates per year in those aged 70 and older.¹⁶

Cognitive impairment is a complex demonstrable syndrome with diverse and changing appearances, including emotional symptoms, and cannot be restricted to memory or other focal deficit such as impaired executive function. Only 6% of memory dysfunctions are isolated in cases of subclinical cognitive deficit. One working criterion for mild cognitive impairment (MCI) established in 2003 applied a stepwise algorithm based on three diagnostic features. The first is the patient who appears to lack “normality” but is not demented in appearance. The second is cognitive decline indicated by the patient and/or an informant report and objective cognitive tests. Lastly, the patient is reported to exhibit preserved basic activities of daily living but has minimal impairment in complex instrumental functions.^{12,16,19–26}

Cognitive impairments, in degrees from mild to severe, are associated with several risk variables. Chronically elevated blood pressure, midlife diabetes mellitus, obesity, cardiac disease, history of stroke, alcohol abuse, alcoholism, drug addiction, apolipoprotein E epsilon 4 genotypes, and male gender are some of the factors that increase risk for cognitive impairment in various degrees of severity.^{9–11,19–24} In addition the compromise of several organ systems may lead to cognitive impairments. The most common neurologic causes are dementias; these conditions are most often diagnosed as Alzheimer’s disease, Lewy body disease, Pick’s disease, Huntington’s disease, Parkinson’s disease, cerebellar degeneration, and supranuclear palsy. Cerebrovascular accidents are among the most common causes of cerebral damage leading to impaired cognitive function. Head trauma may also compromise cortical function, perception, storage of information, and overall function. Poisoning by carbon monoxide may induce a state of cerebral dysfunction. Furthermore, electrolyte abnormalities such as severe hyponatremia may result in seizure and cognitive impairment. Organ failure, anoxia, and infectious processes are less common pathological states associated with cognitive impairments.

The initial assessment of a cognitively impaired individual should include a thorough history and physical examination, in addition to a review of the medical record. Important aspects of the history as they relate to pain management should be reviewed (Table 43–1).

Detection of pain in persons who are cognitively impaired is challenging. Behavioral observation–based assessment is required in these patients. Common among pain-related communicative behaviors are frowning, grimacing, sighing, calling out, guarding, fidgeting, rigidity, tense affect, aggressive mood, disruptive behavior, appetite changes, sleep changes, crying, and irritability. Nonbehavioral signs of pain include increased heart rate, increased blood pressure, elevated respiratory rate, diaphoresis, and pupil dilation.²⁷ Although initially developed for the assessment of pain in children, the Faces Pain Scale has been used in the noncommunicative population for pain assessment (Fig. 43–1).

Pharmacologic pain management remains important in patients with cognitive impairments, particularly because some nonpharmacologic methods are not readily available. When pain is detected, treatment can be rapidly initiated. Scheduled dosing is recommended with medications titrated to pain levels by assessing verbal, behavioral, and functional responses to pharmacologic treatment. Clinicians need to consider common side effects of medications and clinically correlate with the current medical issues their patients are experiencing. Patients with delirium and resulting agitation have been shown to receive more opiates and benzodiazepines when compared to cognitively impaired patients in an intensive care unit (ICU) setting.²⁸

The argument for rapid induction of pharmacologic treatment is based on cognitive impairment affecting pain perception, rather than actual pain sensation or the potentially damaging effects communicated by pain that lead to adverse outcomes. The subjective basis of pain supports the idea that analgesic treatment requires tailoring to patient pain levels and titration while reassessing response. The inability to report pain and relief by those with cognitive impairment makes this process especially difficult. Unrelieved or unrecognized pain is more likely due simply to communicative disorders. Thus, as soon as pain is detected by other means, it can be treated.^29,30 Additionally, pain modifies cognitive function by behavioral mechanisms and modulation of previous depressive symptoms. Patients with dementia experience cognitive impairments that are exacerbated by pain.^31,32 For example, a study by Allen et al³³ found that patients with dementia interacted with peers more often when their pain was adequately treated. Many patients with dementia suffer depression, which may be exacerbated by pain symptomatology. The complex relationship between pain and depression benefits from rapid addressment of pain symptoms as well as depression and anxiety, especially in those with cognitive impairment due to dementia.^34,35

A dearth of evidence exists regarding scheduled-in compared to as-needed pain control in cognitively impaired populations. Pain levels are more difficult to assess under a scheduled analgesic regimen as opposed to as-needed dosing. Similarly, overprescribing medications, particularly to those susceptible to exacerbations of underlying cognitive dysfunction, limits choices among several classes of medications. However, whereas some studies have showed that scheduling low-dose, long-acting opioids lessened agitation in patients with dementia, others have reported no significant difference.^36,37 Although narcotics may exacerbate underlying cognitive dysfunction, care must be taken to avoid the side effects of other classes of drugs as well, such as nonsteroidal anti-inflammatory drug (NSAID)–induced gastrointestinal bleeding. The World Health Organization (WHO) step ladder for pain management is commonly utilized for initiation of pain medications in this patient population (Fig. 43–2).

Titration and medication management can incorporate data from subjective self-reports, somatosensory evoked potentials, and autonomic responses to pain. Behavioral and functional responses to medication must be assessed systematically by multiple methods, because many cognitively impaired patients are inaccurate historians.^30,31 When treating patients over time, clinicians may benefit from psychological assessment of pain perceptions, comorbid mental disorders such as depression, and profiles of cognitive weaknesses and strengths.

Morbidities of pain disorders in the cognitively impaired increase with age, influencing the choice of pharmacologic agent. The most common comorbidities for those with mild cognitive impairment are anemia, Parkinson’s disease, breathing difficulties, angina, hypertension, diabetes mellitus, peripheral vascular disease, transient ischemic attack, and self-reported history of stroke or heart attack. Opioids, for example, may cause respiratory depression and increase breathing difficulties, and aspirin may worsen certain anemias. Parkinson’s disease may also be influenced by opioids, which decrease central dopaminergic transmission and may result in dystonia.

It is important to consider not only medication effects on cognition but also their effects on symptoms of associated disease comorbidities. Understanding that individuals with cognitive impairment may have altered pain perception, these patients may in turn respond suboptimally to standard doses of drugs. This further reinforces the perspective that drugs are best titrated to effect or until the indicators of pain are relieved.^38,39

Acetaminophen has been seen as a relatively safe drug for the cognitively compromised, provided they have no strong contraindications.⁴⁰ Most effective for mild to moderate pain, it has its greatest effect on musculoskeletal pain and is safe to use for a prolonged period.^41,42 Strong contraindications include liver failure, and liver function should be measured prior to use. Acetaminophen lacks an anti-inflammatory mechanism, rendering it less effective for chronic inflammatory pain when compared to NSAIDs. Unlike NSAIDS, acetaminophen does cross the blood–brain barrier. Standard dosing can be used for cognitively impaired patients provided liver functions are normal.⁴³

NSAIDs are employed in similar fashion to acetaminophen and are generally considered first-line therapy. Inadequate kidney function is a relative contraindication, in addition to peptic ulcer disease. COX inhibitors can cause ulceration of the stomach, and most recommendations suggest the use of a proton pump inhibitor or misoprostol for prophylactic gastrointestinal (GI) protection.⁴⁰ Some studies have shown a measurable decrease in cognitive function following use of NSAIDs, highlighting the fact that potential remains for exacerbation of cognitive deficits, even with NSAIDs.⁴⁴ NSAIDs are restricted as short-term therapy to avoid renal damage, GI irritation, and other long-term side effects.⁴⁵

Opioids should be reserved for moderate to severe pain.⁴⁶ A common complication of opioid use is constipation, which can be a serious issue for the cognitively impaired, regardless of living status at home or in a long-term care facility. Current recommendations suggest a bowel regimen that includes co-administration of laxatives to mitigate this side effect.^1,47 Although opioids are known to induce delirium and exacerbate cognitive impairment, these possibilities do not preclude their use when indicated.⁴⁸ For example, long-term opioids may produce fewer side effects physiologically compared to long-term NSAIDs in elderly populations, secondary to fewer physiologic alterations to key organs.^40,42 Physiologic responses require monitoring to minimize complications.⁴⁷ For first-line opioid therapy, the literature suggests that cognitive function is not affected by low-dose buprenorphine or oxycodone in elderly hospitalized patients.^49,50

High-dose opioids and NSAIDs impair both cognitive function and balance, which challenges physicians medicating patients with cognitive impairment.^51,52 Muscle relaxants, anticonvulsants, and antidepressants may also be considered in the treatment of pain, although each comes with a unique challenge. For example, muscle relaxants cause drowsiness, and anticonvulsants may be harmful to the renal or visual system.

Several specific opioid agents merit caution. Meperidine should be used with restraint due to an association with postoperative delirium, and the now-discontinued drug propoxyphene with its neuroexcitatory effects could cause dizziness and ataxia.^52–54 Several studies have suggested opioid rotation to mitigate morphine-induced delirium and potential renal impairment secondary to morphine toxicity.^55,56

Generally, tricyclic antidepressants (TCAs) should be avoided secondary to their association with cognitive impairment, as well as anticholinergic effects and orthostatic hypotension.⁴⁰ Further, TCAs have many drug interactions and must be used with scrupulous oversight.⁵⁷

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) may be used to treat neuropathic pain with fewer side effects and risks compared to tricyclic antidepressants.^57,58 Although largely considered safe, these drugs have been shown in some studies to be associated with a higher risk of falling.⁵⁹ Long-term corticosteroid use should be restricted to patients with chronic inflammatory disorders, excluding osteoarthritis.⁴⁰

Muscle relaxants such as baclofen, cyclobenzaprine, and methocarbamol are less well tolerated in the cognitively impaired. Increased side effects such as sedation, anticholinergic toxicity, and weakness are common, and these medications should be avoided.⁶⁰

For neuropathic pain, the anticonvulsants pregabalin and gabapentin have demonstrated efficacy.^57,61 Despite a generally safe profile, side effects like dizziness, somnolence, fatigue, and fluctuations in weight are common.⁶² Care should be used to assess whether these side effects challenge the caregiver or patient.

For patients undergoing operative or procedural measures, regional anesthesia provides highly effective, intense, and site-specific analgesia and is associated with fewer side effects than parenteral opioids. Return to functional status may be enhanced as well. Concentration difficulties, tendencies to sedation, postoperative nausea and vomiting (PONV), cognitive deficits, disruption of daily living activities, and postoperative immune dysfunction may be minimized when regional anesthesia is employed in a surgical or procedural setting. Axial and peripheral blocks for perioperative pain management are supported by extensive literature. Analgesic benefits from regional anesthesia continue to be supported and demonstrated, but ethical questions need to be answered when considering these and all methods for those with cognitive impairment. The issue of consent for cognitively impaired individuals creates a special challenge for those attempting to provide proper pain management, for example, with regional anesthesia. In these cases, communication is decreased, and therefore proper pain assessment and consent are difficult to complete fully and legally. The medical plan of action then depends on the clinician, the patient situation, patient or legal caretaker consent, and underlying patient pathophysiology.⁴ An additional consideration should be whether regional anesthesia can be safely performed or is contraindicated because of previous patient disease process or current medication regimen.

Nonpharmacologic pain management methods are an integral part of patient care plans for most individuals with chronic pain. Whether viewed as supplementary or the main focus of pain management, nonpharmacologic mechanisms aid in pain amelioration and can be of benefit for those with cognitive impairment. Nonpharmacologic approaches include heat compresses, cold compresses, massage, physical exercise, relaxation techniques, meditation, music, distraction techniques, cognitive-behavioral therapy, acupuncture, and transcutaneous nerve stimulation.^1,37 Little research has specifically addressed these methods in patients with cognitive dysfunction. However, it is recommended that they be applied in these populations, because the risk is low and most do not require robust cognitive ability. Some evidence suggests that the use of these techniques with combined pharmacologic therapy enhances the therapeutic effect of the medications.^1,63

It may be beneficial to recommend that patients schedule times of activities such as performing activities of daily living or light ambulation if able. Yet some studies have demonstrated that inappropriate scheduling of activities can lead to increased agitation levels in persons with dementia or cognitive impairment. This has the potential to increase pain levels and damage outcomes.^64,65 Some examples of appropriate sensory-altering activities are sorting through laundry, washing fruits and vegetables, singing or playing familiar songs, visiting an aquarium or zoo, and outings for coffee. These types of activities may be sensory-stimulating or sensory-calming depending on the participant.^64,65 Whatever the sensory alteration is, the best outcomes are derived from activities that are seen as enjoyable and of positive value to the patients, thus working to improve mental health by decreasing pain.