Delirium is a common complication of dementia, especially as dementia advances. Any brain injury, especially one as profound as most causes of dementia, lowers the threshold for developing delirium in response to a given toxic, metabolic,
or infectious insult. History is again the guide here, as a sudden deterioration in a demented patient, particularly if associated with agitation or other manifestations of distress, should be considered an episode of comorbid delirium until proved otherwise. Resolution of the delirious episode may restore the patient’s mental state and functioning back to the best recent baseline level, but is unlikely to improve cognition further owing to the underlying dementia.

Alzheimer’s disease (AD) accounts for more than half of all cases of dementia in the United States (12). Either alone or as a comorbid condition with AD, vascular (multi-infarct) dementia accounts for the great majority of dementias not diagnosed as AD (12, 13). The incidence of dementia increases with age. Between 2% and 4% of the population over 65 have dementia due to AD, with the prevalence increasing to 20% or more among those aged 85 and older (1).

The common causes of dementia are incurable and invariably lead to the death of the patient. Treatment is palliative from the time of diagnosis. Care largely involves helping patients and families cope with relentlessly progressive debility, manifest in terms of declining cognition, diminished intake and consequences of poor nutrition, frequent infections, and loss of capacity for self-care and mobility. The course of advancing dementia varies greatly among individuals and the loss of functional capacities does not progress in a uniform or predictable way. However, there are consistent patterns of signs, symptoms, and functional loss that herald the final stages of dementia (Table 39.1) (14).

Given that most dementias are incurable, the only available treatments are palliative, and advancing dementia invariably leads to death, it would seem that end-stage dementia is a natural fit for hospice care. Access to hospice care has been improving in recent years for patients with dementia, but this patient population is clearly still underserved by hospice and palliative care programs (14, 15, 16). This is largely due to the difficulty in predicting mortality in end-stage dementia with accuracy, because the eligibility for admission to hospice care in the United States is based on a medical prediction of mortality within 6 months.

The National Hospice and Palliative Care Organization (NHPCO) has prepared a set of model hospice admission guidelines for noncancer diagnoses, including dementia (17). The intent of these guidelines is to help clinicians identify a population of patients very likely to die within 6 months if a given disease runs its normal course. For dementia, the guidelines are based on the Functional Assessment Staging (FAST) scale (18). Eligibility for hospice care under these guidelines requires that the patient be at or beyond the most advanced stage (Stage 7) measured by this instrument. This phase of a dementing illness would be characterized
by inability to walk, dress, or bathe independently, bowel and bladder incontinence, and loss of all capacity for meaningful communication. Presence of any of a number of common complications of advanced dementia can strengthen the case for hospice eligibility (e.g., aspiration pneumonia, pyelonephritis, septicemia, multiple decubitus ulcers, recurrent fevers, weight loss, hypoalbuminemia) (17).

By the time dementia progresses to the point that the patient is considered eligible for hospice care in the United States, the patient and family have typically dealt with the consequences of dementia for years. Many important decisions about the goals and direction of care (e.g., decisions about tube feedings, aggressiveness of treatment with antibiotics) may have already been made without the participation of the palliative care team. Care provided directly to the patient may be limited to physical symptom control, comfort, and prevention of complications that can produce suffering. Patients with dementia rated 7 or higher on the FAST scale are beyond the capacity to benefit from much of the psychological, social, interpersonal, and spiritual care that characterizes palliative care and hospice. Although family members can still benefit greatly from the care of the hospice or palliative care team, the current system of determining hospice eligibility does not facilitate making all the benefits of palliative care available to patients with dementia.

Not only does the 6-month prognosis requirement of the NHPCO criteria serve as a hindrance to providing palliative care through hospice before the patient’s ability to benefit more directly, the criteria leave much to be desired in terms of their capacity to predict 6-month mortality in patients with dementia. Studies using the NHPCO eligibility guidelines for dementia show that the guidelines have a positive predictive value (as measured by the proportion of hospice-eligible patients who died within 6 months) of only approximately 35% (10, 19).

Multiple barriers impede access to hospice and palliative care for patients with advanced dementia. Retrospective review of deaths from dementia reveal that only approximately 10% of deaths were anticipated 3 months in advance, contributing to extremely low rates of hospice referral (16). Additionally, some of the components of excellent palliative care and hospice, such as careful attention to nutrition, meticulous nursing care, and management of infections and other secondary complications of dementia, can prolong survival. Although these interventions may be consistent with goals and preferences of patients and families, they complicate end-of-life care for demented patients if hospice programs avoid admission or recertification of these patients for fear of regulatory scrutiny if patients survive longer than 6 months (14).

The goal of palliative care is to achieve the best quality of life for patients and their families. Palliative care interventions typically focus on providing assurance of nonabandonment to patients and families, aggressive symptom control, assistance with specific life goals, integration of the end-of-life experience and assistance with losses, grief, and bereavement (14). Given the advanced state of dementia when most patients come to the attention of palliative care, symptom-control measures are often the most helpful interventions available.

Agitation and restlessness are among the most common and most troublesome complications of advancing dementias. Determination of specific causes of restlessness, including untreated delirium, pain/discomfort, or depression should be the first step in management. Behavioral interventions (e.g., reassuring contact with familiar others; familiar environmental cues; soothing music) and determination and correction of any precipitants of agitated behavior, if patterns of behavior exist, can be very helpful (20). Pharmacologic interventions for agitation in dementia include cholinesterase inhibitors and memantine (see subsequent text), antipsychotics (see subsequent text), anticonvulsants (e.g., valproate, carbamazepine, gabapentin), benzodiazepines, serotonergic antidepressants (particularly citalopram and trazodone), buspirone, and β-blockers (20). Preliminary evidence suggests that valproate may slow the progression of AD (21). Benzodiazepines should be used with caution, because paradoxical disinhibition (and worsening agitation) is common when patients with dementia are treated with these drugs. “Sundowning”—a pattern of increased agitation occurring in the evening—should lead to the consideration of the presence of delirium (due to the characteristic sleep/wake cycle disruption), sleep disturbances, or the timing of medication administration (22).

Advancing dementia is often complicated by hallucinations, ranging from pleasant or reassuring perceptions of the presence of absent or deceased friends and relatives to disturbing, frightening, or bizarre experiences. Although antipsychotic medication should be used for the treatment of disturbing hallucinations, these phenomena are often poorly responsive to pharmacotherapy and, if problematic, should also be managed with support, reassurance, and distraction/redirection. Generally, progressive memory loss leads to delusional thoughts, commonly manifest as accusations by the patient, that family members or other caregivers are stealing from the patient (when items have simply been misplaced), delusional beliefs that family members are impostors, or delusional accusations of marital infidelity. Family members may need particular support to cope with delusional accusations by the demented patient. Delusions and hallucinations are predictors of more rapid progression of dementia (23).

Although depression is a common complication of the early to middle stages of dementia, patients are typically unable to generate complaints of depressed mood or accurately guide therapy by reporting target symptoms by the time they are treated in a palliative care setting. Antidepressants may be effective in reducing agitation and restlessness, which may be the only manifestations of depression a patient with advanced dementia is able to demonstrate. Additionally, it is advisable to maintain antidepressant therapy as long as it is safe and well tolerated if it has been determined to be beneficial earlier in the course of dementia.

Pain is a common complication of advanced dementia and there is no evidence that demented patients suffer less with pain simply because they are unable to complain about it (24). Pain behaviors and reporting may be reduced as a consequence of impairments in memory, verbal capacity, motivation, and complex thinking. Further, any degeneration of the central nervous system that involves the sensory cortex or structures that relay, process, or mediate pain signals could produce, distort, or otherwise complicate pain in ways that might well amplify the pain experience and the suffering that pain causes (14, 24). For example, patients with vascular dementia would be at higher risk for other cerebrovascular lesions (e.g., thalamic infarctions), which could produce distressing and treatment-refractory central pain syndromes. Those who care for patients with advanced dementia should therefore be especially vigilant to screen for pain and potentially painful comorbid conditions.

The course of dementias, even the course of cases of AD, varies greatly. In the typical case of AD, cognitive deterioration as measured by the Mini-Mental State Examination (MMSE) (25)
is in the range of 3–4 points lost per year. The average duration from onset of symptoms to death is 8–10 years, with the end stage of the illness lasting as long as 2 to 3 years (1). Neurodegenerative changes of dementia do not cause death directly, but death occurs as a consequence of secondary complications (e.g., infections; poor nutrition, and immobility leading to organ system failure). Most older patients with dementia have comorbid medical problems, which can often accelerate the course of the patient’s terminal illness, depending on their severity and reversibility.

One of the core elements of good palliative care is the emphasis on collaboration with the patient and family in determining the goals of care and the priority of various possible intervention in light of those goals. Because many of the palliative goals of care are more subjective in nature than goals that might be pursued earlier in the course of an illness, the preferences, values, and priorities of the patient are actively sought and integrated into plans of care and resulting actions. Unfortunately, by the time most patients receive palliative care for dementia, their cognitive impairment precludes any meaningful participation in this process. Further, it is relatively uncommon for patients with dementia to have discussed their preferences, values, and priorities with the individual who will serve as their designated or default proxy for healthcare-related decision making. Although the ideal situation would involve incremental decision making over the long course of a dementing illness, allowing maximal participation of the patient in the process as long as possible and permitting professional caregivers and proxy decision makers to understand trends in the patient’s preferences, values, and priorities, this is seldom the case. The more proxy decision makers understand the patient’s perspective on decisions (e.g., antibiotic therapy; nutritional support or tube feeding, cardiopulmonary resuscitation, transfers to other settings for treatment of acute or emergent problems), the more likely they will be to understand their role as speaking on behalf of the patient and as the individual who best knows the patient’s preferences, values, and priorities as opposed to perceiving themselves as holding their loved one’s life in their hands. This process works best as a dialogue continuing over time and across several sessions. Exploration of the meaning of decisions to forego life-prolonging therapies and the burden on the proxy decision maker should be pursued in combination with gentle but clear information about of the burden of continuing such therapies, always in the context of the patient’s preferences, values, and priorities, to the extent that they are known.