When given the diagnosis of Alzheimer's or any kind of dementia, the average patient and his or her family members has gathered through news, movies and pop culture enough information to understand what this elusive thief will take away. That memories will continue to fade and cognitive function will wane are understood fairly well, since these are the hallmarks of the disease. But while these outcomes are rightfully at the forefronts of their minds, the reality is that day-to-day hardships and derivatives of disease and aging will undoubtedly become more evident. Here, we talk to specialists about the neurologist's role in identifying and treating pain, addressing behavioral issues, and managing incontinence in patients with dementia.

Though Alzheimer's disease itself is not associated with painful manifestations, patients with dementia are prone to the same painful conditions that afflict non-demented patients in the same age group (such as osteoarthritis, peripheral neuropathies, diabetic neuropathies, etc.). "Chronic conditions increase with advanced age, and most of these are associated with pain," explains Joseph Shega, MD, Assistant Professor of Medicine in the Division of Hematology and Oncology at Northwestern University Feinberg School of Medicine. Despite misconceptions to the contrary, patients with dementia experience pain. "Peripheral nociception does not change," in patients with dementia, Dr. Shega explains, "How pain is processed in the brain may change with cognitive impairment."

Importantly, studies, including a recent one by Dr. Shega and colleagues,1 suggest that many patients with dementia are able to accurately self-report present pain experience when questioned. While patients may not mention ongoing pain to the physician without prompting, those with mild to moderate dementia will typically provide reliable reports if asked directly. "The biggest barrier to assessing patients' pain is that you actually ask the question and not expect them to bring up the complaint," Dr. Shega says.

Patients with mild to moderate dementia generally are able to provide verbal responses to pain queries while patients with more advanced disease may require alternative approaches. Dr. Shega suggests always asking the patient about pain and encouraging a verbal self-report first. If such response is not possible, consider using visual scales. Although these have not been vigorously evaluated in studies that would support their widespread use, they can be beneficial for helping to quantify the patient's experience.

Pain is difficult to identify in some patients with more advanced dementia partly because of communication. While the perception of pain may be intact, the expression of pain seems to modify with the cognitive changes. "Memory also interferes in communicating about pain," says Marti Buffum, DNSc, RN, Associate Chief of Nursing Service for Research at the VA Medical Center in San Francisco. "That is, a person might state they have pain, but then they may forget: 1) that they had said they had pain when one asks further or brings them an analgesic, 2) had agreed to take an analgesic, 3) evaluate the effect of an analgesic, 4) that they had taken an analgesic."

Sometimes the only possible assessment is based on the caregiver's perception through direct observation, according to Sophie Pautex, MD, Pain and Palliative Care Consultation in the Department of Rehabilitation and Geriatrics, University Hospital Geneva in Switzerland. As different studies have demonstrated that caregivers often underestimate a patient's pain, validated observational pain scales must be used, she says. "Using the same scale over time is the best approach to track changes reliably. It is important to take the time to find the most appropriate scale for each patient and ensure that it is understood."

When patient self-reporting is not possible or reliable, Dr. Shega suggests that caregiver reports of actions that suggest the experience of pain may offer some insight. Whether using visual scales or (and) caregiver reports, clinicians must consider their inherent limitations, Dr. Shega urges. For example, some behaviors can be indicative of other feelings or sensations besides pain. Similarly, a patient could point to the frowning face on one pain scale to indicate general discomfort, an unmet need, anxiety, fear, or a combination of these. "It takes a savvy clinician to try to tease out what may be the cause," Dr. Shega says.

To help with identification and monitoring of pain, Dr. Buffum shares her recognition routine:

  • Watch patients over time.
  • Match condition to possible appropriate pain interventions (use the World Health Organization ladder for pain intervention).
  • Evaluate all possible relieving strategies (single intervention, multiple; use alternatives in addition to pharmacologic agents: music, distraction, massage, acupuncture, exercise).
  • Remember that one strategy may not always work and may work at different times.
  • Identify factors contributing to the pain assessed (environment, social situation, other unmet needs).
  • Talk with family and/or familiar others about what types of pain the patient has had and how they relieved the pain.
  • Observe closely how functional status is affected by pain and pain treatment. Get a good baseline assessment even when the patient is severely cognitively impaired, as behavior such as withdrawal can be improved from pain intervention.

Once pain is identified in the patient with dementia, the challenge is initiating an appropriate therapeutic regimen. That challenge is illustrated by several studies that have demonstrated that cognitively impaired patients receive fewer analgesics than do cognitively intact patients with similar pathology, according to Dr. Pautex. Due to potential concerns about interaction with cholinesterase inhibitors (CIs), methodone would not be a first- or second-line treatment option for non-cancer pain in a person with cognitive impairment treated with CIs, Dr. Shega says. Otherwise, most other pain therapies could be considered, depending on the severity and cause of pain.

Dr. Shega believes most experts would endorse the WHO ladder model for pain management, in which severity of pain dictates therapeutic selection. He encourages those seeking more information on pain management strategies to view the guidelines for management of non-cancer pain from the American Geriatrics Society (americangeriatrics.org) and American Pain Society (ampainsoc.org).

There is some concern among clinicians about the effects of opioid analgesics on patients who are cognitively impaired. While he notes, "there are no good studies to really look at the impact of opioids on cognition in cognitively impaired patients," Dr. Shega says, "Most pain experts would recommend a trial of low-dose opioids in the patient who has pain complaints that are not improved with other treatments." Given that pain intensity can increase confusion, it's possible that by reducing pain, opioid analgesics could actually improve rather than diminish cognitive function.

The current approach to management of persistent non-cancer pain emphasizes multi-modal approaches that incorporate both pharmacologic and non-pharmacologic interventions. Non-pharmacologic pain treatment options may be appropriate for some patients with dementia, but the practical benefit of assist devices and other interventions will diminish as the patient's functioning decreases. Nonetheless, clinicians should implement therapies starting with those that are least invasive and associated with fewest side effects and risks. Pain management approaches must evolve as the patient's cognitive capacity decreases, Dr. Shega notes, to match the severity of the pain and the patient's and/or caregiver's needs.

Urinary incontinence is common in patients with dementia, and studies show it's more prevalent in demented than in non-demented older people.2 But while incontinence is frequently attributed to dementia, neurologists must first rule out potentially reversible causes remembered by such mnemonics as DRIPP, according to Thomas E. Lackner, PharmD, Professor in the College of Pharmacy and Institute for the Study of Geriatric Pharmacotherapy at the University of Minnesota. DRIPP stands for:

  • Delirium;
  • Restricted mobility to toilet due to pain, gait disorder, oversedation, or a cluttered path to the toilet;
  • Infection/Inflammation such as atrophic vaginitis, or impaction of feces;
  • Polyuria due to hyperglycemia, hypercalcemia, caffeine, volume overload; and
  • Pharmaceuticals, including drugs to treat urinary incontinence, acetylcholinesterase inhibitors, memantine, alcohol, diuretics, drugs causing fluid retention, sedatives, narcotics, and anticholinergic agents including some antidepressants and antipsychotics.

If addressing these factors is inadequate, non-pharmacologic therapy with lifestyle modifications and—in the appropriate patient (mild to moderate cognitive impairment and/or adequate toileting ability)—a trial of either prompted voiding or habit retraining can be effective.

Pharmacologic therapy is considered if these measures fail to achieve sufficient control of urinary incontinence, Dr. Lackner says. "Pharmacologic therapy is most likely to be effective in individuals with mild to moderate cognitive impairment and/or those who can toilet independently, with supervision, or with limited assistance. Except for immediate-release tolterodine which is not significantly effective for decreasing the frequency of incontinence episodes, medications approved for treating overactive bladder are similarly effective in decreasing urinary incontinence episodes, urinary urgency and frequency, and achieving total dryness."

Dr. Lackner advises there are differences in the incidence of adverse effects between the agents that must be considered when selecting treatment for individual patients with pre-existing comorbidities that could be worsened. The highest rates of dry mouth, constipation, dizziness, and vision disturbances are reported with immediate-release oxybutynin. Dry mouth, however, is less common with transdermal oxybutynin and solifenacin. Four weeks treatment with oral extended-release oxybutynin 5mg/day was recently shown to be well tolerated in nursing home residents with mild to severe dementia.

Many caregivers and family members may assume that incontinence is a nuisance but not much more, especially in comparison to the weight of a neurodegenerative diease. But there are short- and long-term risks associated with incontinence that need to be considered. Making sure everyone involved in the patient's care knows how to help prevent and manage these is important, Dr. Lackner notes. He lays out the potential complications (and remedial treatment) of not managing urinary incontinence:

  • Insomnia. Schedule a diuretic before 3 pm.
  • Depression. This may be improved with improved incontinence or trial of antidepressant therapy.
  • Perineal dermatitis. Improved urinary incontinence, structured skin care program including skin protectants when necessary, change absorbent products often enough to keep the skin dry of urine.
  • Urinary tract infections. Evaluate and treat urinary retention, avoid anticholinergic drugs such as diphenhydramine alone and in many over-the-counter products such as Tylenol-PM, Advil-PM, and cough and cold products, narcotics.
  • Delayed healing of pressure ulcers. Decrease urinary incontinence, assure optimal treatment and conditions for wound healing, avoid/limit use of urinary catheter.
  • Falls. Treat urinary urgency, frequency and nocturia, and mitigate other risk factors for this. "In addition," Dr. Lackner adds, "There are economic costs related to these complications of urinary incontinence."

Another matter is functional incontinence, a type of potentially reversible incontinence often seen alone or together with other types of incontinence in the patient with dementia. "All conditions contributing to functional incontinence must be addressed," Dr. Lackner says. "For example, better control of pain aggravated by walking can enable the patient to toilet in a more timely manner. It also increases the willingness of the patient to toilet by alleviating the fear of experiencing more severe pain associated with toileting."

Behavior and Psychological Issues
Many people with dementia show some behavioral or psychological symptoms at some point during the course of the disorder.3 Identifying patients who need help for behavioral and psychological issues and finding the difference between frustration and "acting out" can be difficult.

"Behavioural and psychological symptoms are heterogeneous," says Geir Selbaek, MD, PhD, of the Research Centre for Old Age Psychiatric Research, Innlandet Hospital Trust in Norway. "In my daily work I prefer to talk about agitation, apathy, depression, psychosis, anxiety and so on. Even these groups of symptoms are multifaceted." Dr. Selbaek recommends physicians primarily identify symptoms by means of reports from the nurses or relatives who are most familiar with the patients and use ratings scales (Neuropsychiatric Inventory, Cornell Scale for Depression in Dementia). "Often you see Ôacting out' as a result of frustration. It is often difficult to identify the frustration. What you see, however, is the acting out. This notion is in line with the concept of Ôunmet needs,' advocated by Cohen-Mansfield."

While the safe and effective treatment of behavior and psychological symptoms are a key priority, it is a priority that is a long way from being achieved.4

Dr. Selbaek believes nonpharmacologic alternatives should be tried first, reserving medications until the symptoms are very severe. "This particularly applies to the use of antipsychotics. If they are to be used, the treatment should be closely monitored and the medication should be discontinued after three to six months even if it is effective," Dr. Selbaek says. This is due to the potentially deleterious side effects of these drugs. "On the other hand, there is no clear evidence that other groups of psychotropic drugs are effective in treating agitation, anxiety, psychosis or depression in patients with dementia."

In their piece on neuropsychiatric symptoms in dementia, Ballard et al.4 say that neuroleptics remain the foundation of pharmacological treatment, although meta-analyses indicate that they are mainly beneficial for the short-term (up to 12 weeks) treatment of aggression in people with AD, and there have been increasing concerns about serious adverse effects like mortality. "The evidence is limited for other pharmacological approaches for the treatment of agitation, and psychosis in people with Alzheimer's disease is limited, but post-hoc analyses do indicate that memantine may be a promising therapy and aromatherapy may be a useful alternative," they write.

Further, autopsy studies indicate that the adrenergic system may be an important therapeutic target. Clinical experience suggests that antidepressants are effective in people with severe depression in the context of dementia, but the evidence base regarding the broader value of antidepressants is far from clear. Of course, "If the patient is not responding to alternative therapeutic strategies and if he/she is clearly suffering, I would certainly prescribe psychotropic drugs—antipsychotics, antidepressants or antidementia drugs," Dr. Selbaek says. "But I would follow the patient closely and discontinue the treatment if it fails to improve the symptoms or if serious side effects occur."

Dr. Selbaek's first line treatment are antipsychotics. If the patient has prominent visual hallucinations, Dr. Selbaek might use cholinesterase inhibitors as a first-line treatment. This would certainly be the case if the patient has Parkinsonism or Dementia with Lewy bodies. Antipsychotics may worsen the cognitive function of the patients, and this issue has to be closely monitored. In nursing homes most patients are using many drugs (in Norway, six drugs on average), he adds. "This means that the response to the Ôseventh' drug may be very different from what would happen if this was the first medication the patient received."

Keep to the well-established slogan in old-age psychiatry: start low and go slow, he says. Concerning antipsychotics, he would prescribe a considerably lower dose than with younger patients, though this does not apply to antidepressants where he uses similar dosing regimens with younger patients. If successful, Dr. Selbaek tries to discontinue antipsychotics after three to six months, antidepressants after nine months.

Recent reports have highlighted the risks of atypical antipsychotic drugs—including increased mortality—and the US Food and Drug Administration (FDA) has issued black-box warnings concerning their use. "Initially I was disconcerted by the reports. And I still am. However, newer studies have demonstrated that the increased mortality also applies to traditional antipsychotics," Dr. Selbaek says. But he argues that the evidence for effect is better for atypicals than for traditional antipsychotics.

Recent discussions on this topic underline the need to monitor these patients carefully. "I still consider atypicals to be the first choice if antipsychotics are to be prescribed. I think they are indicated when the patients manifest severe psychosis or agitation (particularly aggression) and when other approaches have proved to be inefficient. These patients have severe symptoms. Improving these symptoms might be worth the increased risk of serious adverse events, and I don't think any risk condition should entirely preclude the use of antipsychotics," he says.