Agitated behaviors occur frequently in patients with dementia. These behaviors affect the quality of life of the dementia sufferers and their caregivers. For example, these behaviors can greatly complicate everyday management in familiar surroundings and in institutional care, and they predict premature nursing home admission.

Dementia and depression are the two most prevalent psychiatric disorders in the elderly. Although dementia has traditionally been viewed as a disorder of cognition, and depression as a disorder of mood, this simple classification has recently been questioned, and the complex interrelationship between depression and dementia is being elucidated (Emery & Oxman, 1992; Raskind, 1998). Patients with depression may show cognitive deficits, simulating dementia (Berrios, 1989), and patients with dementing disorders may show symptoms of depression (Allen & Burns, 1995; Burns, 1991). In addition, depression may precede dementia and represent the very first signs of dementing illness, or may be a risk factor for subsequent dementia.

Apathy is defined as the absence or lack of feeling, emotion, interest, concern, or motivation (Marin, 1991). Among psychiatric patients, apathy has been subsumed under different terms, such as psychomotor retardation, blunted or flat affect, and avolition, and often occurs in patients with schizophrenia or depression (Marin, 1991). Apathy is also common in patients with dementia (Starkstein et al., 1995), Parkinson's disease (Starkstein et al., 1992), or strokes to specific brain regions (Starkstein et al., 1993).

Anxiety symptoms in dementia can be seen as an expression of stress in predisposed patients who become aware of their cognitive decline. In later stages of the disease, when awareness is lost, the presence of anxiety symptoms cannot be explained as a reaction to this type of stress. The presence of anxiety symptoms in the more impaired patients becomes similar and probably as complex in its etiology and clinical manifestations as other behavioral and psychological symptoms of dementia (BPSD). In this review, we will discuss anxiety symptoms in BPSD.

In mammals, many aspects of physiology vary over the 24-hour day in a predictable, periodic manner. Hormones, such as thyroid-stimulating hormone and melatonin, as well as cardiovascular and autonomic measures such as heart rate, blood pressure, and body temperature all have a predictable diurnal pattern. It is important to understand that such variation is generated internally; that is, such variation represents a fundamental, endogenous circadian variation. Circadian variability is typically distinguished from the numerous exogenous factors that can influence the physiologic parameters in question by its periodic pattern (Turek & Zee, 1999). For example, sleep lowers body temperature, and physical activity, upright posture, food intake, and the state of wakefulness increase body temperature. Such exogenous masking factors can affect body temperature at any point in the 24-hour day. Thus, the behavioral act of going to sleep lowers body temperature, but the fall in body temperature during wakefulness also heralds the onset of sleep and incipient sleepiness. Nonetheless, when all such factors are strictly controlled (by having volunteers confined to supine bed rest with restricted activity, sleep deprivation, hourly isocaloric food intake, and controlled lighting conditions), body temperature continues to oscillate in a highly predictable way, affected only by age, sex, and, perhaps, mental status.

Syndromes are clusters of symptoms that tend to occur together in the same patient. They usually are described crosssectionally (i.e., the symptoms occur in the same individual at the same time) but can also occur longitudinally (i.e., the symptoms occur in the same individual but at different times).

The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) was specifically designed to assess behavioral and psychological symptoms of dementia (BPSD) that would be remediable to both psychologic and pharmacologic intervention. Furthermore, the BEHAVE-AD was designed to assess categories of symptoms that would respond in a cohesive (syndrome) manner in dementia patients, independently of effects of interventions on cognition and functioning. Current data indicate that the BEHAVE-AD does indeed assess a cohesive, cognition- and function independent syndrome in AD and in related dementias that is responsive to psychologic and appropriate pharmacologic intervention. Evidence is also increasing for differential responsiveness of this BPSD syndrome to select pharmacologic agents compared with nonspecific psychologic (placebo) intervention. This article reviews the evidence for this BPSD syndrome in dementia patients, as assessed with the BEHAVE-AD.

Much research has focused on neurochemical and neuropathologic changes in dementia. However, further research is required before definite conclusions can be made about the link between these neurochemical and neuropathologic changes and specific behavioral and psychological symptoms of dementia (BPSD) (Zaudig, 1998). Similarly, the relationship between cognitive status and BPSD has yet to be clarified. Studies investigating the relationship between cognition and BPSD have yielded little consensus, ranging from no association to positive, negative, or mixed findings (Chen et al., 1998). Examples include differences in findings from studies relating the occurrence of psychosis to the severity of cognitive deficits (Ballard & Oyebode, 1995; Molchan et al., 1995; Wragg & Jeste, 1989); failure of some often-quoted associations, such as a relationship between psychosis and the rate of cognitive decline, to hold up under a rigorous critical appraisal of the published data; and contradictory findings regarding the effects of antidepressant treatment on cognition in patients with concomitant dementia and depression (Greenwald, 1995).

Dr. Förstl was impressed by Dr. Reisberg's data showing a close relationship between cognitive impairment and behavioral and psychological symptoms of dementia (BPSD). Yet he questioned Dr. Reisberg's conclusion that cognitive impairment is necessary for developing hallucinations or delusions. Dr. Reisberg responded that although there is no correlation between scores on the Mini-Mental State Examination (MMSE) and BPSD, it does not mean that cognition is not involved in these symptoms. By definition, BPSD are behavioral and psychological. There is a psychological, or cognitive, element to all BPSD, said Dr. Reisberg. As an example, he noted that a patient with cataracts is more likely to experience visual hallucinations. A person who is not cognitively impaired will be able to censor those experiences and not discuss them with others. Patients with dementia do not censor this information, and tell others about their visual hallucinations. Dr. Reisberg noted, however, that visual hallucinations among patients with Alzheimer's disease (AD) are not common, occurring in about 20% of patients, with a peak occurrence just before the final stages of the disease. Dr. Shah commented that BPSD in patients in the final stages of AD may be difficult to detect because techniques for identifying these symptoms in severely cognitively impaired patients are lacking.

Behavioral and psychological symptoms of dementia (BPSD; Finkel et al., 1998) are receiving increased attention in the medical and scientific literature. These symptoms are a principal cause of distress and disability among patients with dementia and their caregivers. Numerous therapeutic studies examining the treatment of these symptoms are being conducted.

Neuroimaging techniques are now common and almost routine as aids in the differential diagnosis of dementia. Structural imaging techniques, including computed tomography (CT) and magnetic resonance imaging (MRI), are used to rule out potentially reversible causes of the dementia syndrome, such as normal-pressure hydrocephalus and brain tumors. More recently and still very much experimental, imaging has been used to identify differences between patients with a particular cause of dementia who have particular behavioral and psychological symptoms of dementia (BPSD), and those without such symptoms. Such comparisons help confirm an organic basis for the BPSD and help elucidate the neural mechanisms that underlie BPSD.

Frontotemporal dementia, or Pick's disease, begins with personality and behavioral changes, in contrast to Alzheimer's disease (AD), which begins with memory deficits. Frontotemporal dementia is a term widely used for both the behavioral-personality component of frontal lobe dementia and for the disease itself (Brun et al., 1994). According to consensus criteria developed by the Manchester/Lund group (Brun et al., 1994), the core features of frontal lobe dementia or frontotemporal degeneration are disinhibition, loss of insight, apathy, disorganization, aspontaneity, indifference, lack of personal hygiene, mental rigidity, perseveration, hyperorality, and utilization behaviors. The clinical features of frontal lobe dementia often overlap with those of primary progressive aphasia, a condition characterized by language deficit in the first 2 years of the disease (Mesulam, 1987). Pick's original patient with lobar atrophy was also aphasic (Pick, 1892), and primary progressive aphasia has a course, eventual outcome, and pathology similar to that of frontal lobe dementia (Kertesz et al., 1994). In some patients with primary progressive aphasia, extrapyramidal symptoms similar to those that occur with corticobasal degeneration and motor neuron disease are superimposed.

Dementia with Lewy bodies (DLB) is the currently preferred term for a variety of clinical diagnoses that have risen to prominence during the last decade (McKeith et al., 1996). These include diffuse Lewy body disease, dementia associated with cortical Lewy bodies, the Lewy body variant of Alzheimer's disease (AD) (Hansen et al., 1990), senile dementia of the Lewy body type, and Lewy body dementia. Initially thought to be uncommon, DLB is now recognized as the second most common pathologic cause of dementia, accounting for up to 20% of all elderly cases reaching autopsy.

Behavioral and psychological symptoms of dementia (BPSD) have long been assumed to be an intrinsic clinical feature of vascular dementia. This assumption is based on case histories and selected series of patients with probable vascular dementia, especially those with small vessel disease, and has been further fueled by the inclusion of features of BPSD in clinical diagnostic algorithms (Cummings, 1994; Hachinski et al., 1975; Wallin et al., 1996). However, controlled empiric research on BPSD in vascular dementia is lacking. The existing literature does not fully support the assumption that BPSD are integral to vascular dementia.

Delirium is a valuable nonspecific sign of physical illness or intoxication and, as clinical teachers, we impress on our students the importance of its prompt recognition and treatment. However, several practical and conceptual difficulties impede the reliable distinction of delirium from dementia.

Dementia encompasses both cognitive and noncognitive domains. Noncognitive symptoms include disorders of behavior, personality, mood, thought content, and perception and impaired functional ability. Behavioral, personality, mood, and thought content disorders have been labeled behavioral and psychological symptoms of dementia (BPSD) following a previous International Psychogeriatric Association consensus conference. Traditionally, BPSD have been poorly studied for several reasons, including the lack of importance attached to cognition in the diagnosis of dementia, the assumption that BPSD are secondary to cognitive and personality changes, the difficulty of accurately defining BPSD, and the paucity of standardized instruments to measure BPSD. Historically, all BPSD tended to be studied together under one broad umbrella and thus older data on individual BPSD are limited. Differing definitions, patient populations, study designs, data collection methods, measurement instruments, and methodologic issues influence the prevalence of the various BPSD reported in different studies, making comparisons between studies difficult.

Several of the presenters in this session focused on behavioral and psychological symptoms of dementia (BPSD) as related to different types of dementia, including frontal lobe dementia, Lewy body dementia, and vascular dementia. A considerable amount of this discussion focused on mixed dementias (patients who might have more than one type of dementia) and the possibility of new syndromes of dementia being identified through autopsy studies and other neuropathologic studies. Dr. Hendrie described an autopsy study that reported that vascular dementia is rare, and that most cases of vascular dementia are in fact Alzheimer's disease (AD) with vascular changes. On autopsy, these patients have the plaques and tangles characteristic of AD, but also have vascular changes. Other researchers have reported that changes related to Lewy body dementia are common in patients with AD. Dr. Hendrie suggested that researchers could learn a great deal if pathologists reported the relative number of plaques and tangles, evidence of Lewy body dementia, or evidence of vascular dementia in each brain, rather than trying to categorize their findings as a single diagnosis.

When an ideal drug for any medical condition is sought, both its efficacy and safety need to be examined. For the treatment of the complex of symptoms that constitute the behavioral and psychological symptoms of dementia (BPSD), much of the literature has focused on antipsychotic agents, including both types of D2 blockers: the conventional neuroleptics and the newer atypical agents. Fewer studies have investigated other medications, such as anticonvulsants, benzodiazepines, betablockers, selective serotonin reuptake inhibitors, and cholinergics.

The original catecholamine hypothesis of affective disorders focused largely on the role of the noradrenergic components of the central nervous system in the etiology of depression and mania (Bunney & Davis, 1965; Schildkraut, 1965). Additional evidence from clinical, pharmacologic, and physiologic studies has emerged since the original hypothesis was proposed and generally supports the view that clinically significant depression can result from a dysfunction of central nervous system mechanisms employing the catecholamine neurotransmitters norepinephrine and dopamine (Jimerson, 1987; Siever, 1987). Neurochemical studies of serotonin (5-HT) receptors and 5-hydroxyindoleacetic acid (5-HIAA) in spinal fluid or brain tissue also suggest an alteration in serotonergic components of the central nervous system in both idiopathic major depression and suicide (Brikmayer & Riederer, 1975; Crow et al., 1984; Lloyd et al., 1974; Mendlewicz et al., 1981; Stanley & Mann, 1983). In contrast to these hypotheses, which suggest that depression may result from the decreased function of one or more central aminergic systems, the cholinergic hypothesis of affective disorders (Janowsky & Risch, 1987) posits that idiopathic depression is associated with the hyperfunctioning of cholinergic systems. This hypothesis is especially interesting in the context of Alzheimer's disease (AD) because the progression of the central cholinergic deficit that occurs in this disorder may interact with the pathophysiology of depression to limit the prevalence of major depression in later stages of this disorder.

The identification of cholinergic contributions to the dysfunction in patients with Alzheimer's disease (AD) appears straightforward at first. However, complicating questions arose more than a decade ago. For example, why, if AD patients indeed experienced cholinergic damage, was the number of cholinergic receptors similar in both AD patients and normal controls at autopsy? Researchers speculated about the possibility of an upregulation of cholinergic receptors in response to the loss of functional receptors subsequent to presynaptic cholinergic neuronal loss. This led to research on the consequences of administering a cholinergic antagonist rather than an agonist in AD patients as a pharmacologic challenge test in an attempt to test the functional sensitivity of the remaining cholinergic receptors.