Dementia

Dementia is a progressive, chronic, and incurable neurodegenerative disorder that results in suffering and loss as patients develop impairments in memory, judgment, language, behavior, and function. Multiple types of dementia have been defined, but Alzheimer’s is the most common type, followed by vascular dementia. The prevalence of dementia increases with age from roughly 1% in persons 60 to 65 years old to approximately 40% in persons 85 years old. The current U.S. population of patients with dementia is roughly 4 million and is projected to increase 10-fold, to approximately 40 million, in the next 40 years. Worldwide, the elderly population with dementia is projected to increase from 25 million in the year 2000 to 114 million in 2050. Patients with dementia are increasingly receiving palliative care for other life-limiting diagnoses, although many die without benefiting from these services. The palliative care specialist therefore needs to be proficient in providing care to patients with early stages of dementia, as well as to patients with advanced dementia who enroll in hospice care with a primary diagnosis of dementia.

Prognosis

The failure to recognize dementia as an incurable and progressive disease may result in inadequate end-of-life care, including delayed referral to hospice. However, it is challenging to determine accurate prognosis in dementia. Prognosis guidelines focus on functional indicators for people with Alzheimer’s disease. For example, the Functional Assessment Staging Scale (FAST) describes the progression of functional decline in patients with dementia in a series of seven stages. In a validation study of the FAST staging system, patients who reach stage 7 (language limited to several words and dependence in all activities of daily living [ADLs]) have a prognosis of less than 1 year. Based on the results of this study, the loss of the ability to ambulate (stage 7c) is particularly indicative of a prognosis of less than 1 year, and it is included as a criterion for hospice enrollment in guidelines for noncancer diagnoses from the National Hospice and Palliative Care Organization. A recent study describes additional criteria that may more accurately identify patients with dementia who have a prognosis of 6 months or less. Data was analyzed from the Minimal Data Set, a federally mandated, standardized assessment that was collected on admission and quarterly for every nursing home resident. The following significant mortality risk factors for nursing home residents diagnosed with dementia were demonstrated: a decline in ADLs, a secondary diagnosis of cancer, congestive heart failure, dyspnea and oxygen requirement, aspiration, weight loss, and age greater than 83 years. A mortality risk index score based on these data was derived that stratifies patients into degrees of risk of 6-month mortality. This study also suggests that hypoactive delirium is a marker of poor prognosis in dementia. Of note, this was a study of patients who were recently admitted to a nursing home, so the results may not be applicable to a wider population. Similarly, in a review of the medical records of hospice-dwelling patients with dementia, age, anorexia, and the combination of nutritional and functional impairment were associated with shorter survival times.

As discussed earlier, it may be possible to identify characteristics that predict poorer prognosis in people with dementia. In addition, acute illness that requires hospitalization may also be associated with poor prognosis. A study of patients with dementia who were admitted to the hospital with a diagnosis of hip fracture or pneumonia found that more than half the patients died within the 6-month postdischarge period.

Pharmacologic Management

In addition to providing information about diagnosis and prognosis, palliative care physicians may need to provide information about treatment options. In the early stages, families and patients often seek guidance regarding potential pharmacologic treatments for dementia. All acetylcholinesterase inhibitors are thought to have similar efficacy. Although a modest benefit was seen in about 30% to 40% of study subjects, the benefit to an individual patient may be difficult to recognize clinically. Therefore, families need to be counseled that, although these medications may slow the progression of the dementia and may result in minimal improvement in functional status, behavior, and memory, it is unlikely that they will significantly improve the patient’s cognition. The side effect profile of the acetylcholinesterase inhibitors, including anorexia, nausea, and weight loss, may be particularly burdensome for older patients, who often have decreasing oral intake. There are very few data to describe efficacy in end-stage dementia. Memantine, an N -methyl-D-aspartate receptor antagonist, was approved by the U.S. Food and Drug Administration in 2004 for the treatment of moderate to severe dementia. It was shown (by Mini-Mental State Examination) to decrease the rate of cognitive decline modestly in patients with moderate to severe dementia. Some clinicians believe that combining memantine with an acetylcholinesterase inhibitor may benefit some patients. However, further research is required before this regimen is made standard practice. Vitamin E, at high doses of 1000 IU twice daily, was shown to delay the time to nursing home placement as well as the time to impairment in ADLs in patients diagnosed with Alzheimer’s disease. However, more recent data suggest a possible trend toward an increase in overall mortality in patients who take high doses of vitamin E, and therefore the risks and benefits of this treatment need to be carefully weighed.

Determining the appropriate time to discontinue dementia-specific medications is a complicated decision. Medication cessation may result in a full spectrum of family response, from significant psychological distress to great relief. The data on efficacy of these medications in severe end-stage dementia are very limited. There may be some benefit of these medications for behavior apart from cognition, so discontinuation may raise concerns of worsening behavioral problems. Moreover, one study suggests that stopping acetylcholinesterase inhibitors and then resuming usage at a future date may result in decreased responsiveness to the medication. Regardless, concerns about side effects, the considerable cost, and perceived prolongation of poor quality of life may lead many clinicians to advise and families to decide to discontinue the therapy, particularly for patients near the end of life and for whom Alzheimer’s dementia is the terminal diagnosis.

Psychiatric and behavioral problems are common in dementia. Palliative care providers who care for patients with dementia can play an important role by offering guidance about these problems to families and caregivers. Depression is common throughout the course of dementia, but it may be easier to recognize in the early stages when patients are better able to communicate and express some insight into their experience. In later stages, behavioral problems such as visual and aural hallucinations, paranoia, agitation, and restlessness are common and occur in up to 80% of patients. Patients may also exhibit physical or verbal aggression and sexually inappropriate behaviors.

For acute changes in behavior, the first step should be to assess for potential delirium with a focused assessment to rule out a reversible medical condition such as fecal impaction or medication adverse effect. After ruling out a reversible cause, the initial management should focus on nonpharmacologic modifications, especially decreasing external stimuli and encouraging family visits or the use of a sitter. Strategies to control behaviors include the creation of a safe, physical home environment, distraction and redirection from sources of anxiety, the identification of nonstressful activities (i.e., day care, groups), and the use of calming, sensory experiences such as aromatherapy, soothing sounds, or touch. There are several well-referenced reviews on treatments for behavioral problems in dementia. However, few randomized, controlled trials have been conducted that substantiate efficacy.

Antipsychotic medications are the main agents used to treat dementia-associated agitation and behavioral problems. These antipsychotic drugs are generally divided into two groups based on side effect profile: typical (e.g., haloperidol) and atypical (e.g., risperidone).

The atypical antipsychotics also have a role in controlling agitated behavior. Several placebo-controlled studies have shown efficacy of the atypical antipsychotic medications risperidone and olanzapine in controlling aggressive behaviors and psychosis in patients with moderate to severe dementia, with virtually no extrapyramidal side effects or tardive dyskinesia. Head-to-head comparisons of haloperidol and risperidone show no difference in efficacy or side effects in the treatment of delirium. Sedation is a notable side effect for all antipsychotic medications, and the development of parkinsonism may limit their use. In addition, the Food and Drug Administration has issued a warning of a possible increased risk of stroke in older people who take any antipsychotic. Recent data also suggest that haloperidol and the atypical antipsychotics are both associated with increased mortality. The atypical antipsychotics (olanzapine in particular) may also predispose diabetic patients to hyperglycemia. Although important considerations, concern for these side effects may not be as relevant for patients close to the end of life or for those cases in which the primary goals are to decrease the severity of behavioral problems and caregiver burden. Given these potential adverse effects, however, it is important to review a patient’s need for antipsychotics periodically and to consider discontinuing or decreasing the medications, if possible. This is of particular importance when caring for patients in nursing homes. Since the passage of the Omnibus Budget Reconciliation Act in 1987 in the United States, physicians must document the indication for the use of all such psychotropic medications in the nursing home setting, as well as intermittent attempts to wean the dose. A systematic review of the pharmacologic treatment of neuropsychiatric symptoms of dementia suggests guidelines for the best therapeutic strategy. Second-line and third-line classes of drugs, including benzodiazepines and anticonvulsants, are discussed in this review.