Reichel’s Care of the Elderly: Clinical Aspects of Aging
5th Edition

Chapter 16
Behavioral Disturbances in Dementia
Constantine G. Lyketsos
Cynthia D. Steele
Martin Steinberg
Dementia is a syndrome defined by a global decline in cognitive capacity occurring in clear consciousness. Most dementia is a chronic illness that is typically progressive and irreversible and that is associated with a range of behavioral and mental disturbances. In this chapter we use the term behavioral disturbances to refer to all noncognitive disturbances in mental life or behavior that may afflict a patient with a dementing illness. Depression, anxiety, fearfulness, delusions, and apathy are all examples of mental disturbances. Similarly, aggression, explosive outbursts, wandering, repetitive calling out, and inappropriate sexual advances are all behaviors that dementia patients may exhibit.
The behavioral disturbances of dementia have considerable importance. These disturbances increase the morbidity of the dementia patient by adding mental suffering and further impairing function. Moreover, these disturbances adversely affect those around the patient, particularly the patient’s caregivers. They add to the complexity of caregiving and increase the time required for it. Behavioral disturbances in dementia are associated with depression, functional impairment, and burnout among caregivers. Additionally, they are associated with a greater likelihood of nursing home placement for the patient with dementia.
While in some cases the behavioral disturbances of dementia have been associated with the brain damage brought on by the dementing disease, this relation is neither completely proved nor the only cause of behavioral disturbance. Dementia patients, by the nature of their condition, are vulnerable to stressors and often respond to such stressors by exhibiting a behavioral disturbance. Thus, for example, aggression in a dementia patient may be the consequence of brain damage to inhibitory brain centers, the result of an otherwise hidden urinary tract infection, or the consequence of an abusive caregiver. Therefore, behavioral disturbance in dementia is not a single entity. Nor do these disturbances have a single cause; rather they are influenced by a range of variables with synergistic effects. For a more thorough discussion of behavioral disturbance in dementia, refer to the report of a recent consensus conference (1). Additionally, a guideline to the treatment of Alzheimer’s disease and related disorders (2) provides an overview of all aspects of the treatment of dementia.
The cumulative prevalence of behavioral disturbances in dementia patients is on the order of 60 to 70% over the course of most dementing illness. The cumulative prevalence of the more serious disturbances, those which involve considerable mental suffering (such as major depression), or some form of dangerousness (such as aggression), is on the order of 40 to 50% over the course of the illness. The prevalence of behavioral disturbances tends to be lower among community-residing patients and more common among patients who attend specialty dementia and Alzheimer clinics at academic medical centers.

The prevalence is even higher among institutionalized patients, such as in nursing homes and psychiatric inpatient units. As expected, the type and the severity of behavioral disturbances differ across these three settings because of selection bias. Table 16.1 is a summary of the cumulative prevalence (i.e., over the course of a dementing illness) of several specific behavioral disturbances.
Table 16.1 Cumulative Prevalence Estimates for Behavioral Disturbances in Dementia Patients
Incidence estimates of the onset of new cases of behavioral disturbance in patients with dementia on an annual basis have rarely been published. With regard to major depression, one study reports a 2-year incidence of approximately 1% in patients with Alzheimer’s disease (3). A different 5-year cohort study suggests that the incidence of depressed mood with vegetative signs is 5% every 6 months and of depressed mood alone, about 14% every 6 months for patients with Alzheimer’s disease (4). The incidence of delusions has been estimated at 17% every 6 months, and the incidence of hallucinations at 9% every 6 months in Alzheimer’s disease (4). Also in Alzheimer patients, the incidence of other behavioral disturbances, such as wandering and aggression, has been estimated at 36% every 6 months (4). Whether these estimates generalize to patients with other types of dementia is unknown.
The persistence of behavioral symptoms over time in dementia patients has been the subject of considerable debate. Few empiric studies have been published. From these it appears that unless treated, behavioral disturbances in dementia are persistent. In a three-site longitudinal study of 335 patients with mild to moderate Alzheimer’s disease there was a high likelihood of persistence of individual behavioral disturbances over 5 years (4). For delusions the probability of persistence every 6 months was 60%. For hallucinations the estimate was 52%. For wandering, physical aggression, and similar behavioral disturbances the estimate was 80%. For depressed mood the estimate was 47%, and for depressed mood with vegetative signs the estimate was 28%. While this was a volunteer clinical sample restricted to Alzheimer’s disease, it is the best study to date and provides good evidence that over time behavior disturbances do not spontaneously remit.

There are several principles important to the assessment and treatment of behavioral disturbances associated with dementia (5). Behavioral disturbances are diverse in presentation and causation, so distinguishing one from another is both possible and necessary. Behavioral disturbances in dementia do not always have a single cause. A variety of contributing causes in predictable domains should be considered case by case. When a new behavioral disturbance occurs, it is necessary to work it up systematically by classifying it and by investigating possible contributing causes before embarking on treatments.
There is no single or universal treatment for behavioral disturbances. Continuing with general supportive patient care and providing a wide range of interventions is critical. Patients must be monitored for response to treatment as well as for side effects, particularly when medicines are used. Side effects tend to occur more often, to last longer, and to take longer to resolve than in elderly patients who do not suffer from dementia.
We propose a systematic four-step approach to any new behavioral disturbance in dementia. The first step, describing the disturbance, has as its main outcome a decision about how to classify the behavioral disturbance. Description begins with the observable phenomena of the disturbance, the behaviors the patient is exhibiting, and places them in the context of the patient’s circumstances, mental state, and physical state of health. This phase requires a careful history from the patient and from one or more collateral sources, typically the primary caregiver. Important factors are the behaviors observed, their temporal onset, course, associated circumstances, and relation to key environmental factors, such as caregiver status and recent stressors. History taking is followed by a careful examination, both physical and neurologic. The mental status of the patient is assessed in detail by an experienced examiner. Laboratory studies may also be needed.
The next goal is to decide whether the behavioral disturbance fits a recognizable pattern. Determining which pattern best describes the situation depends on the clinical circumstance and requires clinical judgment about which aspects of the situation to emphasize. In some cases the clinician emphasizes recognition of a mental syndrome, such as delirium, major depression, minor depression, apathy, or mania, and associates the entire disturbance with this syndrome. In other cases certain disruptive behaviors are being driven by a particular mental state, such as a delusion or a hallucination. Sometimes the disturbance is primarily a disruption in one of the primary drives of sleep, sexuality, or feeding. In yet others the primary emphasis is on the observed behaviors as consequences of behavioral dyscontrol brought about by brain damage from the dementing disease. Finally, some disturbances have the characteristics of a catastrophic reaction (an excessive outburst of emotion and/or disruptive behavior precipitated by the patient’s being confronted with a cognitive impairment) or of an adjustment reaction (such as with a change in routine, a move to a new residence, or the introduction of a new caregiver).
After describing the behavioral disturbance and classifying it, the next step is to decode it. Decoding is looking for causes that may contribute to the onset or continuation of the disturbance. Table 16.2 lists the domains to consider in this process. Medications and general medical conditions have been associated with all types of behavioral disturbance through two additional mechanisms. If the observed pattern most closely resembles delirium, medications and general medical conditions are most likely to be the cause. Particular attention should be paid

to the possible effects of medication accumulation; all medications ought to be considered as possible causes of a new behavioral disturbance.
Table 16.2 Contributing Causes to a Behavioral Disturbance in Dementia
The most common medical conditions associated with behavioral disturbance are a urinary tract infection (both in men and women), dehydration, constipation, pain (such as from osteoarthritis or dental carries), visual impairment, hearing impairment, a viral syndrome (respiratory or gastrointestinal infection), and skin breakdown (particularly in nursing home or in institutionalized patients). Less common are stroke, pneumonia, deep venous thrombosis, and cardiac disease. Additionally, neglect of basic physical needs (leading to hunger, sleepiness, thirst, boredom, or fatigue) that the patient cannot adequately communicate is a cause of behavioral disturbance. In patients who have known chronic medical problems, such as diabetes, hypertension, or cardiac disease, a relapse of one of these conditions should be considered. The next issue is whether the patient is suffering from a new or recurrent psychiatric disorder. In some patients the psychiatric disorder is primary (i.e., not caused by the dementing disease), the recurrence of a lifelong psychiatric disorder, such as major depressive disorder, bipolar disorder, panic disorder, or schizophrenia. All of these may recur in the context of dementia and appear as a behavioral disturbance. In other patients the disorder is secondary to a factor other than the dementing disease, typically a general medical problem (e.g., hypothyroidism, a medication). The disorder may also be due to the brain damage caused by the dementing disease. This is discussed further later in this chapter.
The next part of decoding is to determine whether the behavioral disturbance is related to the cognitive disorder. For example, is the patient irritable because he or she is forgetting things or getting frustrated because he or she can’t talk? Is the patient forgetful enough to believe that he or she is living in a different period of his or her life and therefore believe that some persons are alive (typically parents or spouses) who are dead? A dementia patient may thus look at himself or herself in the mirror believing that he or she is young and not recognize the person who is there. Most of the behavioral disturbances directly linked to the cognitive disorder present as catastrophic reactions, acute behavioral, physical, or verbal reactions out of proportion to seemingly minor stressors. These include anger, emotional lability, and at times aggression.
The next question is whether there is evidence that the dementing disease has involved brain areas other than the ones associated with the cognitive disorder. Involvement of other brain areas may lead to characteristic behavioral or mental syndromes or secondary and/or organic disorders. Most often these occur with involvement of the frontal lobes, the temporal lobes, and certain subcortical regions.
There are several examples. Disinhibition, expressed in inappropriate social behavior, pacing, wandering, or perseveration may be related to damage to select frontal lobe and basal ganglia areas. Another syndrome consists of exploratory curiosity with hyperphagia and hypersexuality. In animals this is called the Klüver-Bucy syndrome; it is associated with damage to the temporal poles and the amygdala. Damage to anterior frontal and subcortical structures may lead to atypical mood syndromes, both depressivelike and maniclike states. Apathy (6), a state of passive lack of interest, has been associated with damage to the temporal lobes, the cingulum, the dorsolateral frontal lobes, and the caudate nucleus.
Brain damage has been associated with unprovoked aggression, particularly if there is disturbed (usually increased) noradrenergic or dopaminergic neurotransmission. Repetitive or compulsive behaviors have been associated with brain injury to orbitofrontal areas and the cingulum. Delusions and hallucinations have also been related to injury to the limbic system. Finally, disturbances of the basic drives, namely, sleep, sex, and feeding, may appear as the dementing disease spreads to relevant brain areas.
The next component of decoding is to determine whether there is something in the environment that is affecting the behavioral disturbance. Common environmental stressors include disruption of routines, overstimulation (too much noise or too many people), understimulation (few people, with the patient spending much time alone), and other upset peers (patients).
The final consideration should be given to caregiver-patient relations. Almost all patients

with dementia have caregivers. Many of them have more than one at a time. Caring for dementia patients is difficult and requires a degree of sophistication that almost any caregiver is capable of acquiring with proper guidance. However, inexperienced caregiving, dominating caregivers, and caregivers who themselves are impaired through medical or psychiatric disturbances may interact with patients in such a way as to exacerbate or cause a behavioral disturbance. When evaluating a new behavioral disturbance, the clinician should consider the caregiver’s understanding of the patient’s level of condition, whether the caregiver is new to the patient (as is common in nursing homes and with agency nurses), whether the caregiver is approaching the patient properly, and whether there are too many caregivers involved in the patient’s care. Most of these sorts of problems occur in nursing homes. However, many occur in private homes, particularly if patients do not have established routines or the caregiver is impaired by a physical or mental disorder.
Once a behavioral disturbance has been classified and decoded, the stage is set for devising interventions to treat it. There are several types of interventions. First are preventive interventions, which include the development and maintenance of daily routines, the provision of routine primary medical care, attention to the patient’s sleep and eating patterns, safety measures to prevent accidents, teaching caregivers about the practical aspects of dementia care and behavioral disturbances, and linkage with experienced and accessible professionals to help assess and treat a behavioral disturbance. Second are interventions that address and remove the cause of behavioral disturbances, such as the discontinuation of an offending medication or the treatment of a bladder infection. Third are attempts to apply behavior management techniques (7) or special programs for dementia patients with disruptive behaviors in nursing homes (8). Finally, there are specific or empiric interventions targeted at particular disturbances. These may include psychotropic medications, electroconvulsive therapy (ECT), or bright light therapies.
A single intervention rarely makes a dramatic difference in a patient’s condition. A variety of concurrent interventions are usually necessary. Most of these involve changing the patient’s environment (rather than changing the patient) to fit the state of impairment or to meet needs. Decoding provides clues on interventions that may be tried. If recent medicines seem temporally related to the onset of the problem, these ought be stopped or reduced. If the patient has a large medication burden, efforts should be made to reduce the burden. If the evaluation reveals a medical problem such as constipation or a urinary tract infection, this should be treated as soon and as effectively as possible, and time should be allowed for the patient to recover fully.
Dementia patients may require a week longer to recover from routine medical problems than nondemented elderly. If a patient has a recurrent psychiatric disorder, it should be treated in standard ways. (An exception to this is the limited ability of dementia patients to engage in insight-oriented psychotherapy.) If a patient’s behavioral disturbance appears closely linked to the cognitive disorder itself, efforts should be made to reduce the likelihood that he or she will face these deficits. If a patient becomes lost and confused in a familiar environment in the evening, the caregiver should attempt to structure the patient’s time more in the evening and to provide more one-on-one attention at that time. If the problem is a specific mental syndrome associated with damage to particular brain areas, it should be treated specifically, often with a pharmacologic agent.
If the problem is linked to the patient’s routine, appropriate changes should be made. Patients may need more frequent meals and snacks so that they are less likely to be hungry; they may require more personal attention from caregivers; or they may need simpler levels of activity. If the problem relates to the caregiver’s approach, caregivers should be taught how to approach patients and manage their behavior by sophisticated clinicians. Such education is best provided through modeling by an experienced clinician in the environment in which the problem is occurring during the time of day the problem is most likely to occur and with regular repeat teaching sessions to reinforce the lesson.
Once a set of interventions for a particular behavioral disturbance has been planned, specific

implementation plans should be mapped out to determine whether they work. This map ought to include who shall do what intervention when, how long it is expected for individual interventions to take effect, and what will be done if interventions fail. When mapping out a treatment approach, fallback plans are very important, as it may be necessary to attempt several interventions before a patient improves. A fallback plan also gives caregivers, who are with the disturbed patient day in and day out, a sense that something is being done and helps maintain their morale. A fallback plan should provide for an intervention if a crisis occurs (e.g., if the patient becomes unmanageable, hospitalization should be available). In our experience hospitalization on an inpatient geropsychiatric unit benefits many seriously behaviorally disturbed dementia patients.
An important consideration in determining the outcome of treatment is the use of standardized assessment scales. Several such scales have good reliability, validity, and clinical utility. These may be used to describe the type and severity of a behavioral disturbance as well as to assess response to interventions. Four scales are recommended for their wide availability and relative ease of use. The Neuropsychiatric Inventory (9) quantifies 10 types of behavioral disturbance in dementia, each on a10-point scale, assessing both frequency and severity of disturbance. It is most useful when clinicians are interested in a broad set of disturbances, as it is short and can be administered by a clinician who is not a physician. The Dementia Signs and Symptoms Scale (10), which assesses 6 types of behavioral disturbances, is most effective in quantifying mania and irritability. Finally, the Cornell Scale for Depression in Dementia (11) and the Apathy Evaluation Scale (12) may be used to quantify depressive disturbances or apathy.
It is important to sustain the treatment plan once it is initiated. Many times the onus to sustain the plan is on the caregivers. The clinician should be sensitive to this and make it easy for the caregivers to implement the plan. Also, when using medicines, clinicians should be alerted to the fact that side effects occur more often, last longer, and take longer to remit than in the general population, so that as few medicines as possible should be used as briefly as possible and at as low a dose as possible. The rule “start low and go slow” applies. Adjustments of medicines should be made over periods that are longer than routinely practiced with other elderly patients. In this era of managed care pressures, it is always tempting to adjust medicines rapidly. This may lead to short-term benefits, and the patient may seem quieter or less explosive, but it may lead to side effects associated with rapidly escalating medication doses.
See Table 16.3 for pharmacologic treatment options. For more detail on the use of psychopharmaceuticals in general, see Hyman et al. (13).
Table 16.3 Medications to Treat Depressive and Other Behavioral Syndromes in Dementia
Clinical Features
The hallmark of delirium is impairment in sensorium. Patients whose sensorium is impaired are distractible, inattentive, disoriented, and hard to engage in a conversation. Most develop a range of mental symptoms, such as irritability, visual or auditory hallucinations, misperceptions, delusions, affective lability, depression, euphoria, and social withdrawal. Some patients are hypervigilant, active, and easily startled. Others are lethargic, withdrawn, or hard to arouse. Most cases of delirium develop suddenly and are reversible after treatment of the causes, often an acute general medical problem. In patients with dementia, particularly moderate to severe dementia, the assessment and recognition of delirium are complicated, since the level of impairment in cognition makes it difficult to determine whether the sensorium is impaired. The cognitive impairment may wax and wane and give the impression of fluctuations in sensorium. Certain dementing diseases, such as cerebrovascular dementia and diffuse Lewy body disease, are accompanied by chronic delirium. In these patients the waxing and waning in sensorium can occur at any point through the day and intermittently throughout the course of the week.

The deliria that accompany dementia are hard to treat, particularly if they are chronic. Environmental modifications to improve orientation, such as good lighting, one-on-one attention, supportive care, and attention to the patient’s personal needs and wants, are central aspects of treatment. If delirium is chronic and consistently accompanied by a sleep disturbance, efforts may be made to stabilize the sleep disturbance through the use of bright lights (14) or medications (see sleep under the section on drives). Pharmacologic intervention is warranted if patients are aggressive, engaging in other dangerous behaviors, or having delusions or hallucinations. Neuroleptic therapy is preferred. Haloperidol 0.25 to 0.5 mg before bed is a first-line treatment option. Alternatives include risperidone 0.25 to 0.5 mg before bed or any other high potency neuroleptic, such as thiothixene or trifluoperazine. Patients with Lewy body dementia often develop parkinsonism on low doses of neuroleptics. In that case a nontraditional neuroleptic, such as risperidone, olanzapine, clozapine, or quetiapine, may be tried first. Patients should be monitored carefully for side effects, in particular sedation, dry mouth, blurred vision, constipation, urinary retention, worsening of delirium, orthostatic hypotension, parkinsonism, dystonia, and akathisia, all of which may occur with neuroleptics. Other alternatives are the benzodiazepines, such as lorazepam 0.25 to 0.5 mg 1 to 3 times per day, although these should be used infrequently and in extreme situations. Trazodone 25 to 75 mg may calm anxious, confused patients for a short time, until behavioral strategies take hold.
Mood Disturbances
Clinical Features
A wide range of mood symptoms have been described in dementia patients, including irritability, anxiety, and dysphoria. Irritable or anxious patients are upset, emotionally aroused, explosive, and at times hostile. They often can be redirected and calmed down. Others are emotionally

labile, with moods ranging from sadness to irritability to explosiveness over short periods with or without environmental provocation. These symptoms are typically nonspecific and rarely require pharmacologic treatment. More often they are best dealt with by reassuring, distracting, and spending time with the patient.
A variety of mood syndromes have been described in dementia patients. The most common is minor depression, in which patients have mild anhedonia, social withdrawal, and occasional sadness. They may feel depleted and exhibit mild neurovegetative change. Rarely are patients with minor depression self-deprecating; rarely do they show other cognitive symptoms of depression, such as guilt, self-blame, hopelessness, or low self-esteem. The syndrome of major depression is characterized by anhedonia or sadness accompanied by impaired vital sense (insomnia, anorexia, low libido, fatigue) and the feeling of being a burden on others, decreased confidence, decreased hope, and decreased self-esteem. Many depressed dementia patients deny feeling sad or depressed but acknowledge anhedonia or mental depletion or are reported by their caregiver to be sad or to cry at home. Minor and major depression are most common in patients whose dementing disease first affects frontal-subcortical circuits, such as Parkinson’s disease, Huntington’s disease, and stroke. A significant number of patients with Alzheimer’s disease and other dementias, however, have major or minor depressive syndrome.
Mania and manialike episodes also affect dementia patients. Classic mania with euphoria, increased talkativeness, increased energy, decreased sleep, flight of ideas, and grandiose ideas is seen occasionally. More often in dementia, manic syndromes take on atypical presentations with irritability, explosiveness, mood lability, decreased sleep, increased pacing, and overconfidence. Some patients develop delusions of grandeur, although these are not common. Maniclike states may be most common in advanced dementia patients.
All treatments for the depressed, irritable, maniclike, and anxious states should be preceded by a workup as discussed in the decoding section. This should be followed by efforts to provide the patient with routines, distraction, predictability in the environment, and optimal physical health. Most cases of major depression and many cases of minor depression require antidepressant therapy. Although the use of antidepressants in dementia is not well established through placebo-controlled trials, there is evidence from case reports and series to support their use. First-line agents are the selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressants. The SSRIs are preferred because they have a lower side effect profile. Sertraline is probably the best starting agent, given its shorter half-life than fluoxetine and a lower likelihood of anticholinergic side effects than paroxetine. An alternative starting agent is nortriptyline. Table 16.3 lists the antidepressants most commonly used to treat depressive symptoms in dementia, including starting doses, weekly dose increases, and peak doses, beyond which additional benefits are unlikely.
Persistence in the treatment of depression is important. After a first agent has failed at an adequate therapeutic dose for 6 to 8 weeks, an alternative agent should be tried. Venlafaxine, bupropion, nefazodone, and the monoamine oxidase inhibitors may be considered. For patients who are partial responders to an antidepressant, boosting strategies using lithium carbonate 150 to 600 mg a day, fluphenazine 0.25 mg a day, or thyroxin 50 to 100 μg a day may be considered. The advantage of boosting strategies is that the patient may respond within a week or two. If he or she does not respond, the booster ought to be discontinued. If a patient continues to be depressed after several antidepressant trials, particularly if there is danger, such as with serious weight loss or suicidal ideas, ECT should be considered. This is the fastest and most efficacious treatment for major depression, and it has a favorable safety profile in dementia (15) despite the stigma associated with it.
Treatment of mania and of emotional lability or irritability typically begins with the use of mood-stabilizing agents followed by neuroleptics. Given its low side effect profile, divalproex sodium (DVS) is the first choice. In dementia patients, the starting dose is 125 mg twice a day.

The dose should be titrated up slowly to a blood level as close to 100 ng/dL as possible. A good way of monitoring for the side effects of DVS in dementia patients is to check for nystagmus and ataxia, which reflect the concentration of free drug in the serum. To prevent rare but serious liver or bone marrow toxicity, liver tests (primarily transaminases) and complete blood counts must be monitored. Alternatives to DVS are carbamazepine, lithium carbonate, gabapentin and the neuroleptics (Table 16.3). Carbamazepine, starting at 100 mg twice a day and increasing to a blood level between 8 and 10 ng/dL if tolerated, with monitoring of liver tests and complete blood count, is an acceptable alternative for mania, maniclike states, lability, or irritability in dementia. As with DVS, the complete blood count must be monitored. Lithium carbonate starting at 150 mg a day and increasing to a blood level between 0.5 and 0.8 mEq/dL is usually tolerated by dementia patients and can have good therapeutic effects, although it has a low therapeutic index and must be used with caution. Patients taking lithium must have serum creatinine and thyroid functions checked quarterly. There is also clinical evidence that gabapentin starting at 300 mg twice daily and increasing to 2 g daily in divided doses has efficacy in treating these disturbances.
Any one of the neuroleptics in Table 16.3 may also be used. Combination therapies of neuroleptics and mood stabilizers or combinations of mood stabilizers may also be considered. The latter are best used only by experienced clinicians. Side effects of mood stabilizers include tremors, gait instability, falls, sleep disturbances, slurred speech, other cerebellar signs, bone marrow suppression, and hepatotoxicity, particularly with DVS.
Psychotic Disturbances
Clinical Features
Delusions are fixed, false idiosyncratic beliefs. The most common dementia-associated delusions have persecutory themes and are not greatly elaborated. For example, patients may insist that they are not in their home when they are. They may also believe that others are stealing their belongings or their spouse is unfaithful. As a result they may try to leave and go home, hit their spouse, or hide their belongings. However, they are unable to elaborate the delusions further, although they may be quite fearful. Significant minorities of dementia patients exhibit delusional misidentifications, hypochondriacal delusions, or grandiose delusions. Bizarre delusions, such as of extraterrestrials, or delusions of passivity, such as those seen in schizophrenia, are extremely rare in dementia patients. Mood-congruent delusions associated with depression, such as delusions of poverty or body rotting, or those associated with mania, such as grandiose delusions, are also seen in dementia patients in the context of these mood syndromes.
It is easy to explain away a delusion in a dementia patient by attributing it to the cognitive impairment. However, most dementia patients do not have delusions. Also, delusions are fixed, and patients cannot be talked out of them even with contravening evidence. Delusions may direct behavior, such as driving patients to aggression, to elopement, or to other actions, such as barricading themselves in their rooms.
Hallucinations are perceptions without a stimulus. Visual and auditory hallucinations are equally likely to occur in dementia. Some patients develop olfactory, gustatory, or tactile hallucinations. Patients with dementia and coexisting visual disturbances may manifest the Charles Bonnet syndrome, in which they hallucinate small people, children, or other live creatures. Similarly, patients with auditory impairments may exhibit auditory hallucinations. Hallucinations are very real and extremely distressing to patients. They may also lead to aggression.
Delusions or hallucinations, whether occurring independently or in association with mood syndromes, typically require pharmacologic treatments. However, sometimes pharmacologic treatments are not indicated, particularly if patients are not disturbed by these experiences or if the experiences do not lead to disruptions in the patient’s environment that cannot otherwise be controlled. The preferred pharmacologic treatments are neuroleptics, which are listed in Table 16.3. Their use has been supported by clinical trials, case series, and case reports. Low-potency

agents, such as thioridazine, are more likely to cause sedation, orthostatic hypertension, constipation and urinary retention, and other anticholinergic side effects than strong neuroleptics, such as haloperidol. The latter are more likely to cause extrapyramidal side effects, such as parkinsonism, akathisia, and dystonia. All neuroleptics have been associated with neuroleptic malignant syndrome and all except clozapine, with tardive dyskinesia. Tardive dyskinesia is most likely in patients who are brain injured, female, or elderly.
The choice of first-line agent to treat delusions and hallucinations in dementia depends on side effect profile. Low-potency medications are preferred because patients with dementia are more susceptible to extrapyramidal symptoms than to sedation or orthostatic hypotension. However, the scientific evidence suggesting one or the other as first-line choice is limited. The clinician should choose either a high- or low-potency antipsychotic as first-line agent and observe for response and side effects. If patients do not respond or if they develop side effects, an alternative neuroleptic should be chosen, preferably with a different side effect profile. Rarely, psychotic symptoms respond to mood stabilizers or lithium carbonate.
In patients with Parkinson’s disease or parkinsonism who are psychotic and who cannot tolerate neuroleptics, a trial of ondansetron 12 to 20 mg/day may be considered for the delusions (16). Also, there is some evidence that a cholinomimetic agent such as physostigmine, donepezil, or tacrine (17) may ameliorate the delusions of Alzheimer’s disease.
Disturbances of the Drives
Clinical Features
All major drives, including feeding, sleep, and sexuality, may be disrupted in patients with dementia. Many lose weight slowly over a long time. This is unexplained. Weight loss is associated with early disease stages, when patients may forget to eat or are unable to prepare meals or feed themselves. However, weight loss occurs in dementia patients even when their food intake is supervised. Some speculate that patients with dementia are less active and therefore require fewer calories. Clinical experience suggests that over time most patients equilibrate and stop losing weight. They may become thin although usually not cachectic.
Patients from time to time develop overeating and gain significant amounts of weight or stop eating almost completely and lose significant amounts of weight. Both of these circumstances should be dealt with immediately, particularly if patients are losing weight. Overeating is commonly associated with Klüver-Bucy syndrome. Undereating is typically associated with a general medical problem (possibly cancer), pain on swallowing, trouble swallowing, constipation, depression, paranoia, or delusions. When patients are losing weight and have stopped eating, they should carefully be assessed for these conditions.
Disturbances of sleep occur frequently in dementia patients. Most common are insomnias with patients staying up late, then falling asleep in the early morning and sleeping late into the day. Some patients develop complete reversal of the sleep-wake cycle. Few patients with dementia develop hypersomnia. Those who do are in the very advanced stages of disease, regressed and chair- or bed-bound.
Sexual disturbances also afflict dementia patients (1819). These have been inadequately studied. Some patients, particularly men, may develop hypersexuality, manifested by inappropriate propositioning, inappropriate touching, or public displays of masturbation. In women with dementia, repeated touching and rubbing of the genital area may be the result of vaginal infection, uterine prolapse, or similar physical problems. Often, hypersexuality accompanies irritability or maniclike states. It may also occur in association with aggression and Klüver-Bucy syndrome. Isolated hypersexuality has also been reported.
Treatment for hyperphagia is best accomplished through behavioral measures such as restricting the patient’s access to food and providing supervision and structure. If the hyperphagia gets out of hand and leads to morbid obesity (this is quite rare) or if it is associated with the other elements of Klüver-Bucy syndrome, pharmacologic efforts to reduce appetite with an

SSRI, such as sertraline or fluoxetine, or one of the stimulants, typically methylphenidate, may be attempted.
Treatment of weight loss involves treatment of the underlying cause, whether it be a medical problem (such as carcinoma), depression, or paranoia. Concurrently, supportive care is provided, along with an aggressive effort to maintain nutrition. Treatments for depression, delusions, or paranoia should be attempted as discussed earlier. ECT should be a primary treatment consideration for a depressed patient who is losing weight. A nasogastric tube or intravenous nutrition may be used temporarily in a patient who is severely malnourished and who is undergoing ECT treatment.
Treatment of insomnia and sleep-wake cycle disturbance should begin with improvement of sleep hygiene. This consists of efforts to get the patient to go to sleep late every day, around 10 or 11 PM, while keeping him or her in a dark room for as long as possible into the next morning. Attempts should also be made to provide sufficient activity and to prevent patients from falling asleep during the day. Many sleep-wake cycle disturbances involve disruption of the body clock; these may respond to bright-light therapy in the morning for approximately an hour using 10,000 lux lights at 3 feet. If the sleep disturbance is associated with depression, suspiciousness, or delusions, that condition should be specifically treated.
For primary sleep disturbances with which bright-light therapy and good sleep hygiene are not successful, hypnotics such as trazodone 25 to 150 mg at bedtime, chloral hydrate 500 to 1500 mg a day, or zolpidem 5 to 10 mg a day may be used. Benzodiazepines are best avoided for treatment of sleep disturbances, since they have to be given chronically and carry a propensity for addiction or cognitive disturbance in dementia patients.
If hypersexuality occurs in association with another recognizable syndrome such as mania, treatment of the specific syndrome should be attempted. In men with dementia who are dangerously hypersexual or aggressive, a trial of an antiandrogen (2021) may be attempted to reduce their sexual drive. Patients may be tried on progesterone 5 to 15 mg orally a day at first. If they respond well, they may be treated with 10 mg of depot intramuscular progesterone every 2 weeks to maintain a reduction of sexual drive. An alternative treatment to reduce sexual drive is leuprolide acetate 5 to 10 mg intramuscularly every month; this agent is also an antiandrogen.
Clinical Features
Apathy is a state of reduced motivation and interest in the absence of sadness or lack of enjoyment (6). Patients are socially withdrawn and uninterested, and they may sit in a chair or lie in bed most of the day. They may agree to participate in activities but then make no effort to do so. Apathetic patients are not sad or anhedonic, do not report fatigue, do not worry or ruminate, and are not anxious or fearful of the future. Apathy is well studied and can be quantified reliably with the Apathy Evaluation Scale. It is likely to occur in any type of dementia, including Alzheimer’s disease, vascular dementia, Huntington’s disease, and Parkinson’s disease. Apathy may be mistaken for depression and treated as depression. Also, apathy in the eyes of some caregivers is a state that should be corrected. These caregivers may attempt to get apathetic dementia patients to do things that do not interest them. This may provoke the patient to explosiveness, resistance, or aggression.
Apathy does not always produce morbidity and mental suffering in and of itself. However, it may appear to independent observers that apathetic dementia patients are sad or unhappy. Additionally, there are concerns that apathy may lead to deconditioning if patients spend much of their time doing nothing. When patients are suffering from apathy or are becoming deconditioned, it is reasonable to attempt specific apathy treatments to see whether patients show more interest in day-to-day activities. However, if the primary problem of apathy is the demands that the environment or the caregiver is placing on the apathetic patient and the patient seems content, it is best to recommend modifications to the environment or to the caregiver’s behavior so as to reduce

the demands on the patient. If there are good reasons to reduce patients’ apathy, a variety of pharmacologic measures may be tried. Apathy has been associated with reductions in dopamine, serotonin, and acetylcholine neurotransmission. Thus, rational pharmacologic treatments include the antidepressants, amantadine 50 to 200 mg a day, levodopa, methylphenidate, and other stimulants (all of the latter augment dopamine neurotransmission). The augmentation of acetylcholine neurotransmission through the use of cholinesterase inhibitors such as tacrine or donepezil may also be considered.
Aggression and Agitation
Clinical Features
Agitation and aggression (22) are nonspecific terms used to describe a variety of disturbances. When a patient is described as agitated or aggressive, it should first be clarified what is meant by the term. In many cases agitation refers to an activated state in which patients are driven, pacing, irritable, delusional, or hallucinating. It is preferred that the behavioral disturbance be classified along these more specific lines rather than be called agitation. The same is true for aggression, which may occur in the context of any of the other behavioral disturbances discussed. Agitation or aggression occurring in the context of any other behavioral disturbance should be thought of as secondary to another disturbance so that its treatment follows treatment of the primary disturbance.
At times, often in patients with severe dementia, aggression or agitation occurs in isolation and cannot be classified otherwise. The most common forms of such aggression are verbal (yelling, threatening) and physical (slapping, punching, biting, and hitting), often in the context of daily care or toileting. Verbal aggression is more common than physical aggression. Usually physical aggression does not carry sufficient force to damage property or seriously hurt others, although it can be quite damaging at times. Aggression may also occur after some other provocation from the environment, such as when other nursing home residents approach and invade the patient’s personal space. Unprovoked aggression, in which a patient approaches and hits someone, throws things, or kicks at the wall, is much less common. Unprovoked aggression is seen most often in advanced or severe dementia patients. Any episode of aggression should be decoded, with interventions designed to target contributing causes. When decoding does not reveal any other obvious cause of the aggression, it is reasonable to believe that the aggression is intimately related to the dementing disease.
Behavioral approaches to aggression, such as distraction, supervision, routine, and structure, are critical and should be tried first. Behavior modification approaches using token economies, rewards, and other contingencies have been reported to reduce some aggressive behaviors. Since unprovoked aggression is infrequent (events occurring once a week or less often), it is very difficult to develop and implement a consistent and sustained behavior modification plan. Many clinicians resort to pharmacologic interventions. Sequential trials of the following may be considered for unprovoked aggression: neuroleptics, antidepressants, mood stabilizers (divalproex sodium, carbamazepine, lithium, gabapentin), buspirone, β-blockers (which in animal studies have suggested the ability to block aggressive acts), antiandrogens, and benzodiazepines.
The success rate of treating unexplained and unprovoked aggression in dementia has not been established. With each medication trial there is probably no more than a 10 to 20% chance of benefit with the commensurate side effects that accompany the medicine. At times, patients with unprovoked aggression require restraint to prevent harm to others. Restraint may be in the form of sedation and/or physical restraint, such as a geriatric chair. If restraining measures are necessary, careful supportive care should be provided to the restrained patient. Over time, efforts should be made to reduce the amount of restraint and to determine whether the patient can tolerate independence without becoming aggressive. The ability to wean from restraint after episodes of unprovoked aggression, even in severe dementia, has repeatedly been observed in clinical practice.

Calling Out
Clinical Features
In moderate and severe dementia, particularly in institutions (probably because of selection bias), some patients call out intermittently in a disruptive way (23). The calling out may take the form of calling somebody’s name, asking for help, requesting something specific (something to drink or eat), moaning, or unintelligible vocalizations. Many of these calling out behaviors (at times called clazomania) are secondary to a medical problem or another psychiatric syndrome. They may also occur independently, presumably as a consequence of brain damage from the dementing disease. Calling out is a particularly disruptive problem in institutions, as it can affect unit milieu and other residents. Also, patients who call out appear to be suffering, which makes treatment attempts compelling.
Clinicians should first strive to identify what the patient is communicating by calling out and respond to the request. If this fails or if the request is clear but is repeated continuously after it has been addressed, nonspecific or environment-modifying approaches should be attempted. If these are not successful and the problem persists, it may be necessary to remove the patient from stimulating or noisy environments (dining room, activity area), when the calling out is worst. If the patient appears to be suffering while calling out or if the problem is severely disruptive to a unit milieu, pharmacologic treatments may be attempted. While the likelihood of the success is low, β-blockers, trazodone, buspirone, SSRIs, tricyclic antidepressants (21), neuroleptics, mood stabilizers, and antiandrogens, have been associated with reductions in calling out.
Disinhibition, Stimulus-Bound Behaviors, and Frontal Lobe Behaviors
Clinical Features
Behaviors that suggest disinhibition, such as wandering, intrusiveness, grabbing things, cursing, being distracted by stimuli, inattention, urinating in trash cans, and utilization behaviors, have all been described in patients with frontal lobe dysfunction. Similar behaviors have been described in dementia patients, particularly in those who are severely cognitively impaired. Many of these behaviors are harmless, and patients can be allowed to continue engaging in them so long as they are not suffering and there are no safety issues. However, from time to time these behaviors become problematic, particularly if they lead to aggression or adversely affect caregivers and other patients in institutions. Such behaviors also make patients vulnerable to elopement or victimization (theft, being hit by others).
The preferred approach to these behaviors is to provide behavior management and to increase supervision, if possible with constant or one-to-one observation. This allows patients to continue with their disinhibited routines and provides someone to keep them out of trouble. This is a very labor- and time-intensive approach, although it typically bears fruit. Other approaches include attempts to distract patients. However, given the severity of dementia, by the time patients exhibit these behaviors, it is hard to engage them in new activities. These behaviors resemble the hyperactivity and inattention of children with attention deficit disorder and of adults who have suffered traumatic brain injury affecting the frontal lobes. For this reason, pharmacologic treatments using dopamine augmentors such as bupropion, levodopa, and psychostimulants have had success in treating them. Other treatment approaches may include β-blockers, DVS, and SSRI antidepressants.
Compulsive and Repetitive Behaviors
Clinical Features
Patients with severe dementia at times develop repetitive routinized behaviors. These include repetitive hoarding, tapping, pushing at doors, marching in place, picking in the air, pulling things out of closets, flushing the toilet, putting things in the mouth, and others. These resemble compulsions, although it is impossible to know whether patients are having true obsessions,

given that their mental state is usually not accessible. Most of the time it is best to allow these behaviors to occur, if safe, because trying to stop them may be frustrating and lead to explosiveness and aggression. When patients are suffering or if the behaviors become seriously intrusive to others, attempts to stop them should be considered.
Very little has been presented in the literature about how to approach these specific behaviors. However, their resemblance to compulsions suggests that medicines effective against obsessive compulsive disorders, such as clomipramine, and SSRIs (including fluvoxamine) may be attempted. Behavior modification has not been studied adequately, although our experience suggests that they are not effective for these types of disturbances.
Klüver-Bucy–like Behaviors
Clinical Features
Klüver-Bucy syndrome includes the triad of exploratory wandering, hyperphagia, and hypersexuality. Elements of this syndrome may develop in advanced dementia patients. They may walk around constantly testing doors, pulling at things, and looking into everything, although without a specific purpose. The presence of the entire triad is probably rare in dementia patients, although it definitely occurs, particularly in later stages of Alzheimer’s disease.
Providing nonspecific interventions and tolerating and compensating for these behaviors is probably the best treatment approach. A safe environment, free of hazardous substances that can be ingested and of vulnerable peers, is optimal for this approach to succeed. Pharmacologic treatment may also be used, although chances of success are uncertain. Possible treatments are amantadine, levodopa, stimulants, SSRIs, tricyclic antidepressants, and neuroleptics. Case history reports have noted benefits of these medicines in patients with brain injury, particularly the mentally retarded.
Behavioral disturbances are common in dementia and are an important focus of treatment in all settings with dementia patients. In approaching the demented patient with a behavioral disturbance, it is important to conduct a detailed, systematic evaluation followed by description and classification of the disturbance. This should be followed by decoding to determine contributing causes to the disturbances. Treatment planning is based on the results of the description and decoding of the behavioral disturbances. Effective treatments for behavioral disturbance in dementia include preventive interventions, caregiver education, behavior management, behavior modification, pharmacologic treatments, bright-light therapies, and environmental modifications to accommodate the patient’s condition.
Supported in part by the Copper Ridge Institute. We are grateful to Betty Bourgeois for typing this manuscript and to Glenn Treisman and Diana Klein for their review and comments.
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