Definition

The term “Behavioral and Psychological Symptoms of Dementia” (BPSD) was coined in 1999, being defined as “symptoms of disturbed perception, thought content, mood or behaviour that frequently occur in patients with dementia” (Draper et al. 2012a). BPSD is not a unitary concept but rather an umbrella term that encompasses a number of symptom groups or syndromes; currently, there is limited agreement about syndrome composition, although “agitation,” “moods.” and “psychosis” feature prominently. It is likely that BPSD syndromes have a different prevalence, etiological factors (biological, psychosocial, environmental), prognosis, and hence management implications.

Introduction

In the historical descriptions of dementia by Esquirol in 1838 and by Alzheimer in 1907, behavioral and psychological symptoms were recognized as features of the dementia syndrome (Draper et al. 2012a). For example, Alzheimer’s description of his patient Auguste Deter included symptoms of paranoia, delusions, vocal disruption, and hallucinations in addition to cognitive impairment. Despite this, for many years the focus of clinical dementia research was on the cognitive features, and it was only in the 1980s that an increase in research into the noncognitive symptoms occurred (Draper et al. 2012a).

One of the difficulties in establishing BPSD syndromes has been the term “agitation,” which has been used in a variety of ways by clinicians and researchers. An Agitation Definition Working Group recently used a survey and consensus process to form an agitation definition for dementia and cognitive impairment that has four components: the behavior is consistent with emotional distress; there is excessive motor activity, verbal or physical aggression; the behaviors cause excess disability; and the behaviors are not solely attributable to another disorder (Cummings et al. 2015).

Another difficulty in establishing BPSD syndromes has been the lack of consensus about measurement. Numerous rating scales have been developed to measure BPSD, and there is no single gold standard, with one recent overview article listing 35 scales (Ford 2014). Some of the more commonly used scales are the Neuropsychiatric Inventory (NPI), the Cohen-Mansfield Agitation Inventory (CMAI), and the Behavioral Pathology in Alzheimer’s disease rating scale (BEHAVE-AD). Each relies on the observations of a person who has been in close contact with the person with dementia over the previous 2–4 weeks (depending on the scale used). The NPI and BEHAVE-AD have a neuropsychiatric focus with symptoms being rated in clusters such as delusions, hallucinations, mood disturbance, and sleep disturbance, while the CMAI is more descriptive of individual behaviors such as biting, scratching, screaming, and pacing. Hence, the choice of rating scale might depend on the purpose. There is also a scale that focuses specifically on depression, the Cornell Scale for Depression in Dementia (CSDD).

BPSD occur in almost all people with dementia, with the community-based Cache County Study reporting a 97% 5-year prevalence of any type of BPSD as measured by the NPI. Many types of BPSD tend to persist, with 18-month follow-ups in the Cache County Study reporting that delusions persisted in 66% of individuals, depression in 58%, and aberrant motor behavior in 56%. However, it is noteworthy that population-based studies of BPSD have shown variability of types of BPSD in different countries; for example, apathy is less prevalent in China and Nigeria than in Japan, the United States, Spain, and the UK (Wang et al. 2012). BPSD are particularly common in nursing homes with the point prevalence ranging from 69% to 92% in studies from Australia, Norway, the Netherlands, and the United States (Draper et al. 2012a).

There has been a paucity of research that has explored the relative prevalence of BPSD in different types of dementia (Ford 2014). However, high rates of hallucinations and disinhibition have been reported in Lewy body dementia, consistent with visual hallucinations being one of the core diagnostic criteria for the disorder. Similarly, early behavioral disinhibition is a diagnostic criterion for frontotemporal dementia, which is distinguished from other types of dementia in most studies by the presence of disinhibition, apathy, and aberrant motor behavior. Comparisons of vascular dementia and Alzheimer’s disease have had inconsistent findings, with some studies reporting few differences and others showing higher rates of apathy, depression, and emotional lability in vascular dementia and higher rates of psychosis (most commonly delusions) in Alzheimer’s disease. Depression is more strongly associated with Parkinson’s dementia than Alzheimer’s disease.

Etiology of BPSD

Research into the etiology of BPSD is in its infancy and has mainly focused on Alzheimer’s disease. There is a growing body of research, but much of it is unreplicated. Current models suggest an interaction of a broad range of factors including neurobiological substrates (such as genetic polymorphisms, neurotransmitter changes, neuropathology, medical comorbidity), premorbid personality, psychological reactions, and social aspects including caregiver and environmental issues (Draper et al. 2012b).

There are three main explanatory models of how caregiver interactions might contribute to BPSD. The “stress threshold” model is based on the observation that people with dementia have a lower threshold to coping with stress, with behavioral disturbances occurring when this threshold is exceeded. The “learning theory model” emphasizes the importance of inadvertent reinforcement of inappropriate behaviors; for example, caregivers might only respond to a noisy person when they are calling out and not when they are quiet. The “unmet needs model” recognizes that people with more severe dementia cannot always communicate their needs, such as social interaction, pain relief, hunger, or physical activity; hence, caregivers have the challenge of working out what unmet needs the behavior might represent. The models are not mutually exclusive; it is likely that elements of each might operate simultaneously with the individual circumstances of the person with dementia perhaps indicating which factors might be more relevant in their situation (Draper et al. 2012b).

It is likely that the relative contribution of each of these etiological factors varies according to the specific behavior and type of dementia. Here, we cover some of the more prominent types of BPSD and outline the key etiological factors that have been identified for each.

Psychosis (Delusions and Hallucinations)

In general, psychosis is mainly associated with neurobiological substrates. This includes medical comorbidity, such as infection, hypoxia, or drug toxicity, which may result in delirium with associated acute psychosis, particularly visual hallucinations and paranoid ideation, which develops over a few days. There are often features of agitation present. From a clinical perspective, this is a critically important diagnosis to make due to the high morbidity and mortality associated with delirium.

Psychosis otherwise has a more gradual onset and is more common in females, declining cognition and increasing severity of neuropathology in Alzheimer’s disease. There is preferential involvement of the frontal lobe and/or limbic regions, although visual hallucinations tend to involve the occipital lobes (Draper et al. 2012b). On functional imaging, psychosis is associated with hypoperfusion in frontal and temporal lobes. Some delusions may be explained by memory deficits (e.g., misplacing items and interpreting this as theft) and misidentification of people and place. Although inappropriate caregiver strategies are also reported to be associated with delusions, it is unclear whether these are etiological or reactive to the psychosis.

There is an increased familial risk of psychosis in Alzheimer’s disease as suggested in a study involving the combination of samples from the United States and the UK that found a significant association between proband psychosis status and the occurrence of psychosis in Alzheimer’s disease in siblings with linkage peaks occurring on chromosomes 7 and 15. A meta-analysis of serotonergic system genes concluded that the HTR2A T102C polymorphism is a significant risk factor for psychosis in Alzheimer’s disease. These receptors may also modulate antipsychotic response. Polymorphisms in dopamine receptors have also been associated with psychosis in most studies, particularly D3 genes, where two studies found homozygous (i.e., having identical pairs of genes) carriers of the 1 allele to be at increased risk (Draper et al. 2012b).

In Lewy body dementia, in contrast to Alzheimer’s disease, visual hallucinations, but not delusions, are associated with less tangle burden but more cortical Lewy body pathology and may be related to cholinergic deficits in the temporal cortex. Further, visual hallucinations are associated with hypometabolism in visual association areas rather than the primary visual cortex. However, delusions in Lewy body dementia have a similar substrate to psychosis in Alzheimer’s disease.

Aggression and Agitation

Aggression and agitation are often associated with other frontal symptoms such as disinhibition and may be a reflection of executive dysfunction. Aggression is more common in males and vocally disruptive agitated behavior more common in females. The etiology may be complex, multifactorial, and include medical comorbidities, history of head injury, alcohol and substance misuse, neurobiological substrates of dementia, and social, psychological, or environmental factors. Premorbid personality may also interact with these factors. Verbal and physical aggression may be secondary to pain, physical discomforts (e.g., constipation, thirst, overheating), depression, and other health issues. These behaviors are often best interpreted as a form of communication of distress. Consequently, patients with agitation and aggression have diverse reactions to caregiver intrusion into their personal space, with some improving and others worsening depending on the type of interaction, indicating a need for training of caregivers and tailored interventions.

Neurobiological substrates of aggression and agitation in Alzheimer’s disease are multiple and complex. Genetic factors include polymorphic variations in serotonergic and dopaminergic genes. Dopaminergic, cholinergic, serotonergic, and noradrenergic neurotransmitter changes have been reported in the brain. For example, in Alzheimer’s disease, aggression is linked with choline acyltransferase (ChAT) activity in the frontal and temporal cortices, with reduced ratios of ChAT activity to dopamine D1 receptor binding and dopamine concentration in the temporal cortex. Consistent with this is the finding that on functional neuroimaging, aggression is associated with hypoperfusion of the temporal cortex. Further, dopamine-blocking agents improve aggressive behavior in dementia. Aggression in Alzheimer’s disease is also associated with an increased postsynaptic sensitivity to noradrenaline with a lower concentration of noradrenaline producing an amplified effect. Locus coeruleus neuronal loss, upregulated expression levels of tyrosine hydroxylase mRNA, and an increase in noradrenaline synthetic capacity in residual cells may account for the increased postsynaptic sensitivity to noradrenaline. The dopaminergic system has also been implicated in aggression and agitation in frontotemporal dementia, a type of dementia that has frontal and temporal lobe neurodegeneration, with increased activity and altered serotonergic modulation of dopamine neurotransmission (Ford 2014; Draper et al. 2012b).

Depression

Depression tends to occur earlier in the course of dementia, and for many, it can be the presenting problem. In some individuals, this represents a psychological reaction to self-awareness of early cognitive decline, while in others it appears to be associated with neurobiological changes associated with the evolving dementia, with frontal symptoms such as apathy being associated with more severe depression. Depression is more common in young-onset dementia with some evidence of an increased risk of suicide in the 3 months post diagnosis. A history of depression is also a risk factor for dementia, and so in many there is likely to be a predisposition to further depressive episodes and, as in cognitively intact people, those with dementia may become depressed in the context of stressful life events such as the death of a partner, admission into institutional care, pain, and other physical discomforts. Frustration from impaired communication skills, particularly in those with aphasia disproportionate to impairment in other cognitive domains, can also precipitate depression.

Neurobiological substrates to depression include abnormalities in the serotonergic neurotransmitter system including polymorphisms of serotonergic genes, reduced noradrenaline levels, and polymorphisms in dopaminergic genes. Neuroimaging studies show hypoperfusion (i.e., decreased cerebral blood flow) in frontal, temporal, and parietal lobes to be associated with depression in Alzheimer’s disease (Ford 2014; Draper et al. 2012b).

Apathy

In the absence of depression, apathy is generally a reflection of neurobiological changes. Apathy is associated with frontal-subcortical dysfunction irrespective of the type of dementia. In Alzheimer’s disease, neuroimaging studies show hypoperfusion in frontosubcortical structures, especially the anterior cingulate, while in frontotemporal dementia there is disruption of cortical-basal ganglia circuits. Neurotransmitter changes in Alzheimer’s disease include cholinergic deficiency and a blunted dopaminergic brain reward system (Ford 2014; Draper et al. 2012b).

Clinical Features of BPSD

The hallmarks of dementia are deterioration in aspects of cognition and social and physical functioning. The term BPSD is not a diagnosis in itself but refers broadly to various clinical presentations seen in people with dementia. BPSD is an important development in a person with dementia as it is associated with longer hospital admissions and more complications, more disability, greater likelihood of placement in a residential aged care home, more rapid rate of decline, greater financial costs, reduced quality of life, greater mortality, and significant stress for carers and staff in residential facilities (Draper et al. 2012a). From a clinical perspective, BPSD can be subdivided into behavioral and psychological symptoms.

Behavioral Symptoms

Aggression and Agitation (Verbal or Physical)

Agitation is common in people with dementia, and the prevalence increases with the progression of cognitive impairment. Agitated behaviors may be divided into four subtypes, aggressive, nonaggressive, verbal, or physical. Aggressive behaviors include swearing, screaming, scratching, pushing, grabbing, hitting, kicking, and biting. Nonaggressive behaviors include calling out/repeated requests for attention, being verbally demanding, complaining, excessive/unrealistic anxiety, repetitive questions, phrases, concerns, or sounds, pacing and wandering, rummaging, restlessness or purposeless activity, repetitive movements or mannerisms, hiding things, and inappropriate dressing or disrobing. People with poor social relationships are more likely to be aggressive. Unsurprisingly, aggression and agitation are associated with admission to residential care.

Disorders of Sexual Expression

Sexual disinhibition may be verbal or physical and directed at self or others. These behaviors may be particularly confronting for caregivers and pose logistical problems in residential care. Sexually inappropriate behaviors may range from requests for unnecessary assistance in changing/bathing and genital care to suggestive gestures, disrobing, exposing, or masturbating in public, sexually explicit language, remarks or recounts of sexual experiences, and unwanted physical contact (e.g., kissing, inappropriate touching/fondling/grabbing, sexual advances, and attempts to have intercourse without consent).

These behaviors may relate to lack of an intimate partner, lack of privacy, misinterpretation of cues (e.g., caregivers touching them when assisting with personal care), an unfamiliar or understimulating environment, predementia sexual behavior, medication (e.g., dopaminergic drugs), mood disorders, or psychotic symptoms (Royal Australian and New Zealand College of Psychiatrists 2013).

Sleep Dysfunction

Disturbed circadian rhythm may complicate the progression of dementia and cause considerable carer stress. In dementia with Lewy bodies (a type of dementia characterized by fluctuation in mental state and intermittent confusion, parkinsonism, visual hallucinations, and falls), REM sleep behavioral disorder (which involves the person acting out their vivid dreams while asleep) may occur early and even precede the formal diagnosis of dementia. Sundowning is a term for the onset or worsening of BPSD symptoms in the afternoon or evening. It may also relate to disturbed circadian rhythms. Sleep dysfunction may also relate to comorbid medical conditions (e.g., sleep apnea, congestive cardiac failure, pain, depression), environmental conditions (e.g., room temperature, lighting, changes in the environment), and medication (e.g., diuretics).

Wandering

Wandering is a symptom particularly burdensome for carers, which may lead to placement in residential care. It may include exit seeking and repeated attempts to leave home and aimless walking. Under stimulation, boredom, anxiety, and cognitive deficits in navigation may be contributory.

Psychological Symptoms

Psychosis

Delusions

Persecutory or paranoid delusions are the most widespread type in dementia. Common delusional beliefs include theft, that a spouse/caregiver has been replaced by an impostor (Capgras syndrome), that the person’s residence is not their home, infidelity, and abandonment (Grossberg et al. 2012). Delusions may also be distressing for caregivers and increase the risk of violence toward them, particularly with delusions of infidelity and of impostors. Delusions in dementia are a risk factor for physical aggression.

Hallucinations

Visual hallucinations are the most common type in dementia, followed by auditory hallucinations, with other sensory modalities rare. A common hallucination is of phantom boarders, where the person sees people in the home who are not actually there. Visual misperceptions also occur, when there is a visual stimulus but it is misinterpreted. This may relate to visual agnosias (impaired recognition of items presented visually) or problems with contrast sensitivity.

Misidentification

External stimuli may be misinterpreted leading to misperceptions, which may be held with delusional intensity. The common types of misidentifications are of self (not recognizing one’s own image), phantom boarders (people being in the person’s home), of other people (e.g., a spouse or family member), and of events on television being interpreted as occurring in real time around them. Misidentification includes the defined syndromes Capgras, Fregoli (i.e., believing that a person is someone else in disguise), and intermetamorphosis (i.e., believing that familiar people in their lives have switched identities).

Anxiety

Anxiety may occur on its own or in conjunction with another type of BPSD. Themes may relate to health, the future, finances, and activities or events not previously considered stressful. A common anxious cognition in dementia is fear of being left alone, which may reach phobic proportions. Godot syndrome may also occur, where the person repeatedly asks questions about an upcoming event.

Depression

The spectrum of depressive symptoms is common in dementia, with depressed mood being most common (40–50%), followed by subsyndromal depression and major depression (10–20%) (Grossberg et al. 2012). It can be difficult to diagnose depression due to the overlap with somatic symptoms of dementia (such as weight loss, agitation, apathy, disturbed sleep) and the increasing communication and language difficulties as dementia progresses. A depressive illness should be considered if there is a rapid deterioration in cognition, a family or personal history of depression, pervasive low mood and anhedonia, unexplained acute behavioral change, or if the family is concerned about depression.

Apathy

Apathy is a lack of interest, interactivity, emotion, concern, motivation, and initiation of activities. It is a common symptom, which may occur in up to 50% of patients with mild to moderate dementia. Symptoms of apathy and major depression may overlap, including reduced interest, lack of energy, psychomotor slowing, and poor motivation. Apathy may be distinguished from a depressive illness when amotivation occurs without the somatic and mood symptoms of depression (sadness and psychological distress). The following case demonstrates how a carer may interpret apathy in a loved one with dementia and the commonality with features of depression.

Case 1

Sidney is a 91-year-old man living at home with his wife. He was diagnosed with mixed vascular/Alzheimer’s dementia 6 years ago. His wife refers him for assessment of depression. She complains that for the last year he just sits in his chair and stares at the wall. He no longer waters the plants and even seems to have lost interest in cricket as he does not even turn on the television when sitting in front of it. She is frustrated by how “lazy” he is and that he no longer even helps with the gardening. He does not strike up conversation with her but responds if she talks to him. When their great-grandchildren visit, he smiles and watches them play.

This case is illustrative of apathy with profound lack of motivation, self-initiated activities, and indifference but the retention of warmth and reactivity when caregivers take the initiative to provide enjoyable activities and interactions.

Principles of Management

BPSD may arise for numerous reasons, thus there is no single approach to management. The environmental, biological, psychological, and interpersonal factors should be considered when assessing someone. BPSD may be considered a form of communication, whereby unmet needs are expressed through behavior (Royal Australian and New Zealand College of Psychiatrists 2013). Aspects of the individual’s personality, culture, and personal experiences may also influence their presentation. The first step is to have a clear description of the behavior and to evaluate whether intervention is needed. It may help to have caregivers/residential care staff keep a behavior diary prior to formal assessment. The ABC (antecedent, behavior, consequences) approach may be used to comprehensively describe behavioral problems. Using this method, the clinician records the antecedent events leading to the behavior (the context and any precipitant), the particular behavior, and the consequences of the behavior (for the patient, staff, others).

Delirium must first be excluded in a person with dementia who has an acute change in mental state or behavior. Dementia is a strong risk factor for delirium. The hallmarks of delirium are sudden onset of or new confusion, fluctuation in cognition and level of consciousness, and inattention. The etiology may be multifactorial and include medications, pain, and physical illness. Anesthetics, drug intoxication or withdrawal, and drug interactions, adverse effects, and polypharmacy may be relevant. Drugs of particular concern include psychotropics and those with cholinergic properties. Pain is a prevalent symptom in people with dementia but often unrecognized and undertreated. Common causes of pain include wounds, fractures, urinary retention, poor dentition, constipation, and surgery. Any acute medical illness may precipitate a delirium, so broad potential causes should be considered and treated accordingly. It may take days to several weeks for delirium to resolve, even after the underlying cause is treated.

Nonpharmacological

Nonpharmacological interventions are first-line treatment for BPSD. A person-centered approach emphasizes the importance of understanding the individual- what their interests, past experiences, and preferences are- and how this may inform the management of their BPSD (Royal Australian and New Zealand College of Psychiatrists 2013). For example, past negative experiences of institutionalization may be unwittingly reenacted in residential care, or knowledge of a person’s hobbies may be used to divert them from the behavior or to address unmet needs for stimulation and social contact.

Environment

Environmental factors may contribute to BPSD. A change to the environment, including the interpersonal mix of residents or staff at a facility, may precipitate BPSD. It is important to evaluate whether there are extremes of temperature, lighting, stimulation, noise, or clutter. There is good evidence for unobtrusive safety features improving resident well-being and depression (Fleming et al. 2009). Exit seeking may be reduced by minimizing the number of locked doors or obscuring door handles, so as not to attract attention, and when doors do not have glass panels. An environment that provides a variety of spaces may reduce depression and anxiety, improve social interaction, and help the person find their way around. Single rooms are also beneficial in residential care. Optimization of levels of stimulation is effective, by both reducing unhelpful stimulation (e.g., noise or busy doors) and increasing lighting (e.g., good visual access to toilets). A homelike environment reduces aggression, but it is not possible to disentangle the effects of small unit size, staff skills, and care philosophy or familiar physical environment (Fleming et al. 2009). Similarly, there is moderate evidence for providing opportunities to engage in ordinary activities of daily living (ADLs), but the effects are hard to distinguish from staff factors and the contribution of the environment (Fleming et al. 2009). The provision of outside space is only beneficial if combined with staff interaction. A number of other nonpharmacological treatments may confer benefit in BPSD (O’Connor et al. 2012, see Table 1).

Behavioral and Psychological Symptoms of Dementia, Table 1 Effective non-pharmacological treatments for BPSD
Full size table

Sensory impairment is associated with BPSD and may be reversible. A thorough visual or auditory examination should be part of the assessment of hallucinations and the environment optimized to improve visual contrast and lighting. Inability to speak the local language may act as a sensory impairment by impeding communication. Interpreters should be used to optimize the likelihood of effective communication.

Psychological Approaches

Psychoeducation for caregivers about how to manage BPSD is an effective strategy, with benefits lasting months (Livingston et al. 2005). There is also evidence for behavioral management strategies, which target behaviors of the individual or caregiver. Individual sessions are more effective than groups (Livingston et al. 2005).

There are a few types of psychotherapy, which have been evaluated in people with dementia. Any intervention should be based upon a person-centered framework, which incorporates the unique experiences and preferences of the individual. Overall, evidence is poor, and the methodological quality of studies is weak (Livingston et al. 2005). Cognitive stimulation therapy uses information processing rather than knowledge of facts to stimulate and engage people with mild to moderate dementia in an optimal learning environment. It may reduce depression and improve quality of life, during treatment and for some months afterward. A small pilot randomized controlled trial of a cognitive behavioral therapy-based intervention for people with dementia and anxiety, Peaceful Mind, showed short-term benefits in terms of improved quality of life and reduced anxiety in participants as well as reduced related distress in carers (Stanley et al. 2013).

A number of other psychotherapeutic approaches have been studied but have low or no evidence (Livingston et al. 2005). Validation therapy emphasizes a person’s current feelings as real regardless of the reality of the situation. It encourages and validates expression of feelings. For example, if a person is agitated because they cannot be with a loved one, the therapist using a validation approach will acknowledge their feelings and engage them in a discussion about the relationship. Reminiscence therapy focuses on stimulating memory as it relates to an individual’s life history, e.g., past significant events. Materials such as old newspapers or personal items may be used to stimulate memories and enable sharing of their experiences. Reality orientation therapy involves presenting information about place, time, and important others using visual prompts (e.g., calendars, clocks, personal items, regular family visits, lighting appropriate to time of day). The rationale is that reminders, which improve orientation, improve functioning. This therapy also has low-level evidence.

Pharmacological

Overall, there is only modest evidence for the use of pharmacotherapy in BPSD and risk of clinically significant adverse effects (Royal Australian and New Zealand College of Psychiatrists 2013). Most pharmacotherapy trials, although methodologically sound, are often limited by their short duration and follow-up period and exclusion of non-Alzheimer’s dementias. Nonetheless, medication may be indicated in conjunction with nonpharmacological measures when the BPSD is moderate to severe, poses safety concerns, nonpharmacological interventions have failed, or the BPSD is affecting function or the quality of life of the patient or carer. Informed consent from the patient and their substitute decision-maker is essential.

Key issues to be considered before initiating a trial of pharmacotherapy for BPSD are whether drug treatment is warranted and why; whether the particular target symptom is likely to respond to medication; which class of drug is most appropriate/evidence based; adverse effects of the drug; the duration of drug treatment, and planned review and monitoring of response and adverse effects. Other general principles of prescribing include slow and careful titration from a low dose, consideration of the individual’s medical comorbidities, which may affect drug metabolism and excretion, and avoiding polypharmacy. Particular care must be taken with people with dementia with Lewy bodies or Parkinson’s disease, who have greater sensitivity to antipsychotic medication.

Pharmacological Cognitive Enhancers

Cholinesterase inhibitors are not currently indicated for BPSD. Meta-analyses of cholinesterase inhibitors in BPSD have found statistically significant differences in global neuropsychiatric scores compared to placebo, but clinical significance is doubtful (Campbell et al. 2008). Subgroup analyses show cholinesterase inhibitors may be useful when targeting specific BPSD symptoms, including apathy and indifference, hallucinations and delusions, anxiety and depression, and aberrant motor behavior (Setz and Lawlor 2012). Rivastigmine is significantly beneficial in dementia with Lewy bodies, particularly for agitation and visual hallucinations. Withdrawal of cholinesterase inhibitors may lead to worsening of BPSD within 6 weeks. Adverse effects such as diarrhea, gastrointestinal upset, agitation, bradyarrhythmia, and anorexia may limit use.

Memantine, an NMDA glutamate receptor antagonist may be useful for BPSD. Although it was found to modestly reduce scores on the neuropsychiatric inventory, the clinical significance is uncertain. It may be most useful for target behaviors such as agitation, aggression, delusions, hallucinations, and irritability. It may delay the emergence of agitation in people with dementia. Side effects include dizziness, drowsiness, constipation, hypertension, anorexia, headache, anxiety, delirium, and psychosis (in dementia with Lewy bodies).

Antidepressants

Evidence is lacking for the use of antidepressants in depression with dementia. Nonpharmacological strategies should be used first and antidepressants reserved for when these are unsuccessful or in more severe cases with suicidal ideation. Selective serotonin reuptake inhibitors are first-line agents. Tricyclic antidepressants should be avoided due to the risk of delirium conferred by the high anticholinergic burden. Citalopram, a selective serotonin reuptake inhibitor, may be effective for agitation/aggression and comparable in efficacy to risperidone and more effective than perphenazine (an antipsychotic). Adverse effects may include gastrointestinal symptoms, hyponatremia, falls, and, in citalopram, prolonged QTc interval (an abnormality on electrocardiograph which may predispose to cardiac arrhythmias) at doses 40 mg or greater.

The following case demonstrates the assessment and multimodal management of verbal agitation due to an untreated anxiety disorder.

Case 2

Mary is an 83-year-old nursing home resident with advanced Alzheimer’s dementia and a history of anxiety. She is unable to walk and stays in her room. The staff ask for assistance to manage her constantly calling out “help.” The vocalization has been present for years but has become more frequent and associated with distress in recent months. The general practitioner started risperidone (2 mg nocte), with little effect.

The staff complete a behavioral diary which shows that the calling out is greatest in the evenings and does not occur during bathing or meal times (when she is fed). Sometimes, she grabs at her throat and looks distressed. When her son sits holding her hand, the vocalization reduces. There are no abnormalities on physical examination or pathology tests. The staff have moved her to a room near their station so they can reassure her frequently. This works for a brief time, then she calls out again when they leave. During the assessment, Mary has no spontaneous speech other than calling out “help.” She does not maintain eye contact. Tone is mildly increased in her arms. Her affect is fearful. She nods in agreement when asked about feeling worried and later about breathlessness. The vocalization becomes louder and more frequent as the psychiatrist leaves. Further discussion with staff reveals she used to feed the pet rabbits and sit out in the garden area but has not done so in several weeks due to short staffing. She now shares a room with a non-English-speaking resident. Mary’s son confirms a history of significant anxiety and depression, with several hospitalizations.

The psychiatrist concludes that Mary has a relapse of her anxiety disorder with probable panic attacks. She is likely to be understimulated and lonely. Following discussions with staff, efforts are made to bring her into the dayroom beside English-speaking residents and for her to resume her role of feeding the rabbits. The risperidone is stopped due to lack of efficacy. With consent from Mary’s son, she is recommenced on sertraline, which she responded to previously. The vocalizations reduce over a few weeks; she smiles occasionally at staff and appears less worried. Further review is scheduled to monitor progress.

This vignette demonstrates the importance of comprehensively describing the behavior using the ABC approach while taking into account individual historical factors, the environment, and nonverbal communication. Psychotropic medication may be indicated and useful but should be ceased if ineffective.

Antipsychotics

There is modest evidence for the use of either haloperidol or risperidone for aggression but limited evidence for other agitated behaviors in dementia (Schneider et al. 2006). Aripiprazole may be useful for agitation and aggression in Alzheimer’s disease. Risperidone also confers modest benefit for psychosis in Alzheimer’s disease (Schneider et al. 2006). Quetiapine has been shown not to be of benefit in studies of agitation in dementia with Lewy bodies and Alzheimer’s and may be associated with greater cognitive decline in Alzheimer’s (Royal Australian and New Zealand College of Psychiatrists 2013).

Antipsychotics are associated with several risks warranting consideration. There is an elevated risk of stroke, neurological symptoms (e.g., headache, dizziness, transient ischemic attacks), and mortality, the latter higher in typical antipsychotics. The extrapyramidal side effects are well recognized, more common with typical antipsychotics, and include parkinsonism (tremor, rigidity, bradykinesia), falls, akathisia, and neuroleptic malignant syndrome. Metabolic side effects include hyperglycemia, hypercholesterolemia, and weight gain. Antipsychotics can also cause delirium and cognitive decline, especially those with prominent anticholinergic side effects, such as olanzapine and quetiapine. Ventricular tachycardia, torsade de pointes, and sudden cardiac death may be associated with some antipsychotics. Importantly, several studies have shown that BPSD remain unchanged or improve when typical antipsychotics are discontinued (Ballard et al. 2009).

Benzodiazepines

Benzodiazepines may be used for agitation; however, there are no good studies in BPSD. Use should be time limited, and short-acting benzodiazepines like lorazepam are preferred to reduce the risk of accumulation. Sleep hygiene strategies should be first-line treatment for insomnia and, only if unsuccessful, short-term use of temazepam. Falls, delirium, drowsiness, and ataxia are the main adverse effects.

Anticonvulsants

Meta-analyses have shown that carbamazepine is modestly effective for agitation (Schneider et al. 2006) but inadequate evidence for sodium valproate (Konovalov et al. 2008). Side effects include falls, cognitive impairment, ataxia, blood dyscrasias, and hepatic dysfunction.

Analgesics

Systematic, effective treatment of pain may significantly reduce agitation in nursing home residents with moderate to advanced dementia. Regular paracetamol may be sufficient for the majority of this population and buprenorphine patches required for some.

Electroconvulsive Therapy

Although electroconvulsive therapy may be used for depression, psychosis, and agitation in dementia, especially in life-threatening situations or with symptoms nonresponsive to medication, evidence is restricted to case reports and series. Transient delirium is common after a treatment.

Conclusion

BPSD syndromes are an important and common development in dementia occurring at all stages in the illness. They have significant and far-reaching implications for the person with dementia and their family and caregivers. As well as considering the particular type of dementia, the behaviors or psychological symptoms should be carefully observed and described as part of a thorough assessment. Careful evaluation of the individual’s social circumstances, experiences, personal history, and their medical, psychiatric, and functional history is essential to understanding the potential contributing factors. Management must similarly be tailored to the individual addressing the component causes in a collaborative approach with significant others and carers. Pharmacotherapy should be reserved for situations where other measures have failed and to target particular symptoms known to be responsive to specific medication. A plan for review and ongoing monitoring is essential. Further research that integrates neurobiological, psychosocial, and environmental domains will better develop understanding of the etiological factors underlying these clinical syndromes.

Cross-References