In clinical practice, the behavioral disturbances seen in patients with dementia are helpful in determining disease severity and the need for support care. In patients with Alzheimer's disease, the early appearance of behavioral symptoms is associated with faster disease progression. Until recently, pharmaceutical companies have had little interest in developing drugs to treat behavioral disturbances, because the U.S. Food and Drug Administration, in the “Guidelines for the Clinical Evaluation of Antidementia Drugs” dated November 8, 1990, held that drugs acting on noncognitive symptoms associated with Alzheimer's disease would be “pseudospecific” (i.e., not targeted to the core cognitive domains of Alzheimer's disease). As a result, few measurement scales were specifically developed to assess functional autonomy and behavior in patients with Alzheimer's disease within time frames of 3 to 6 months, the typical length of double-blind, placebo-controlled studies. Many of the existing scales included heterogeneous items relevant to cognition, functional autonomy, somatic symptoms, and psychiatric problems. The Dementia Behavior Disturbance (DBD) scale was developed in the late 1980s, a time when the importance of behavioral symptoms in dementia was increasingly being recognized. Recent harmonization efforts for the development of antidementia drugs have further emphasized the clinical importance of noncognitive symptoms in dementia.

The behavioral symptoms seen in patients with dementia are diverse, ranging from agitation to hallucinations and paranoid delusions. Many patients with dementia have affective disturbances, including depressed mood. To provide a means of assessing the severity of depression and mood changes in demented patients, the authors and colleagues at the National Institute of Mental Health developed the Dementia Mood Assessment Scale.

A dysfunctional behavior can be defined as “an inappropriate action or response, other than an activity of daily living, in a given social milieu that is a problem for the caregiver.” Dysfunctional behaviors commonly accompany cognitive impairment and are a significant source of burden to caregivers. Dysfunctional behaviors may be the first sign of a dementing illness, even before caregivers perceive changes in the patient's cognitive abilities. However, unlike cognitive impairment, dysfunctional behaviors are amenable to medical treatment. Effective treatment of these behaviors requires their description and identification, evaluation of their frequency and impact on the caregiver, identification of causes, development of a treatment plan, and evaluation of the effects of treatment.

The cognitive domain has long been the focus of clinical and scientific efforts in dementia research. Only recently has behavior, and more specifically behavioral problems, been recognized as a legitimate focus of research. In its summary statement of September 1991, the Alzheimer's Association Task Force on Behavior Management noted the following with regarding behavioral disturbances: “(a) the study of assessment and treatment of behavioral problems must develop in its own right as well as complement studies on improving cognition; (b) controlled clinical trials of behavioral treatments of behavioral disturbances are desperately needed; and (c) both standardized rating scales and direct behavioral observations should be used to assess problems and determine treatment efficacy.” [Emphasis added by author.]

The usefulness of data generated by clinical trials of patients with behavioral disturbances of dementia depends heavily on the study design and the measures used to determine patient outcomes. Several rating scales are available to assess general behavioral problems, agitation, and depression in patients with dementia. The appropriate rating tool depends not only on the purpose of the study but also on whether the measure meets the criteria discussed subsequently.

Foreshadowing the following day's presentations on cross-cultural perspectives, Dr. Hendrie raised the issue of how to measure the effect of environment and culture on behavioral disturbances. For example, agitation may disappear when patients are admitted to a hospital, indicating that patient-caregiver interactions or the patient's living environment may be the cause of this problem.

Uncontrolled reports suggest that 25% to 75% of patients with behavioral disturbances of dementia respond to conventional neuroleptic drugs. Yet during the past 20 years, results from only four randomized, double-blind, placebo-controlled trials of neuroleptics in dementia have been published. These studies were conducted in hospitalized inpatients or nursing home residents.

Behavioral symptoms of dementia are stressful not only for patients but also for their caregivers. These symptoms include delusions, hallucinations, activity disturbances, aggressiveness, sleep disturbances, affective disturbances, and anxieties and phobias. Despite the burden of coping with behavioral problems, little information is available about effective treatments for behavioral symptoms in Alzheimer's disease and related dementing disorders.

When behavioral disturbances of dementia can no longer be tolerated by family caregivers or become unmanageable in a nursing home, the clinician must consider appropriate methods of treatment. Some behavioral disturbances may respond to changes in the patient's environment or the approach of the caregiver; for others, pharmacologic treatment is necessary.

The negative effects of behavioral disturbances of dementia on the quality of life of both the patient and caregiver have been recognized for some time. For family caregivers, behavioral problems increase stress and may lead to institutionalization of the patient. In nursing homes, professional caregivers may have difficulty managing behaviorally disturbed patients and avoid interactions with them.

Both pharmacologic and nonpharmacologic methods can be used to treat behavioral disturbances of dementia. Many drugs and drug classes have been advocated as having putative efficacy in treating nonspecific behavioral symptoms; the list includes neuroleptics, anxiolytics, antidepressants (e.g., trazodone), anticonvulsants (e.g., carbamazepine and valproic acid), lithium, β-adrenergic blockers, selegiline, and buspirone. Neuroleptics are among the most commonly prescribed psychotropic drugs for behavioral symptoms and have been described as being “modestly effective” in controlling agitation, both in patients with dementia and in elderly patients in general. To examine the relative efficacy of neuroleptics in treating behavioral disturbances of dementia, the author and colleagues performed a meta-analysis of clinical trials published in the literature from 1954 to 1989.

Although the Nurses' Observation Scale for Inpatient Evaluation is a commonly used tool in nursing home studies of behavioral disturbances of dementia, Dr. Luxenberg noted that this instrument is relatively weak compared with other rating scales. In most nursing homes in the United States, as well as in other countries, nursing aides are the primary caregivers and therefore the primary informants. These aides often have a cultural background different from that of other nursing staff members and may be less likely to accurately report on behavioral problems. Dr. Luxenberg provided an example of a nursing aide who reported that a patient chanted every morning and then refused assistance with bathing and dressing. When the investigator observed this behavior, he found that the patient was praying and refused to bathe until he had completed his prayers.

Patients with dementia may exhibit several types of delusions. Delusions have usually been described as simple and unsystematized paranoid beliefs, such as frequently accusing caregivers of stealing or being insincere or deceitful. Misidentifications—believing that another person is in the house or not recognizing one's own mirror image—also are common in patients with dementia. To further clarify the origin and clinical significance of delusions, the authors studied these behavioral disturbances in patients admitted to the 40-bed Alzheimer Unit at “Fatebenefratelli” Hospital in Brescia, Italy, and in community based patients with dementia.

Studies conducted at our Alzheimer Center in Cleveland, Ohio, along with those of other investigators, have documented that visual hallucinations occur with sufficient frequency in Alzheimer's disease and related dementias to warrant further investigation of their meaning and implications. The largest data set in which frequency of hallucinations among persons with Alzheimer's disease has been examined comes from a collaboration among the National Institute of Aging Alzheimer's Disease Cooperative Study (ADCS), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), and the Case Western Reserve University Alzheimer's Disease Research Center (ADRC). As a part of this collaboration, we examined data from 556 patients with Alzheimer's disease treated at medical centers across the United States who had been rated using the CERAD Behavior Rating Scale for Dementia (BRSD). The BRSD is a comprehensive, informant-based tool that includes several questions concerning the frequency with which hallucinations and misperceptions were experienced during the month before the interview.

Misidentifications are misperceptions (i.e., a form of illusion) with an associated belief or elaboration that is held with delusional intensity. Although misidentifications have been defined in several ways, four main types have been described: (a) presence of persons in the patient's own house (the phantom boarder syndrome); (b) misidentification of the patient's own self (often seen as a misrecognition of his or her own mirror reflection); (c) misidentification of other persons; and (d) misidentification of events on television (the patient imagines these events are occurring in real three-dimensional space).

Behavioral disturbances of dementia are associated not with cognitive decline but with progression of the disease and concomitant functional impairment. Thus, these distressing behaviors occur later in the course of the illness, at a time when caregivers' resources may be sorely taxed. Behavioral disturbances are often cited as precipitating placement in nursing homes.

A wide range of neuropsychiatric disturbances, which include noncognitive behavioral problems and mood changes, can accompany the unrelenting cognitive deterioration seen in patients with Alzheimer's disease. Aggression, agitation, paranoia, hallucinations, sleep disturbances, or depression occur in more than 50% of patients with Alzheimer's disease, both those living in the community and those cared for in nursing homes. Disinhibition, apathy, indifference, fatigability, complaining, and negativism, as well as incontinence, changes in appetite, and sexual disturbances, also occur in patients with dementia.

Emotional lability, intrusiveness, and catastrophic reactions are some of the noncognitive psychopathologic phenomena seen in patients with Alzheimer's disease. These symptoms occur frequently throughout the disease course and strongly influence the well-being of patients with dementia and their caregivers.

Of the numerous behavioral disturbances identified in patients with dementia, depression, anxiety, and sleep disturbances can have a considerable impact on the quality of life of both the patient and the caregiver, particularly if the caregiver is a family member. Our task as clinicians is to identify the most appropriate treatment based on current knowledge of these behavioral problems.

Consensus concepts regarding behavioral disturbances of dementia can be useful for screening populations of patients with dementia. However, these concepts may not serve well as guidelines for treatment in clinical practice. The physician or nurse faced with a husband with dementia and his healthy wife must consider seriously all dementia-related behavioral problems, whether or not they fit within consensus concepts. It also is easier to reach a consensus on highly abstract concepts than to achieve agreement on more practical issues. Cultural differences, both between countries and within the same country, also complicate the consensus process.