Scales
Type of scale*
References
Neuropsychiatric Inventory (NPI, NPI-Q, NPI-C) a
G
Behavioral Pathology in Alzheimer’s Disease (BEHAVE-AD) Rating Scale
G
[3]
Behavioral Syndromes Scale for Dementia (BSSD)
G
[12]
CERAD Behavior Rating Scale for Dementia (BRSD)
G
[13]
Dementia Behavior Disturbance (DBD) Scale
G
[14]
Dementia Signs and Symptoms Scale (DSS)
G
[15]
Multidimensional Observation Scale for Elderly Subjects (MOSES)
G
[16]
Neurobehavioral Rating Scale (NRS)
G
[17]
Nursing Home Behavior Problem Scale (NHBPS)
G
[18]
Cohen-Mansfield Agitation Inventory (CMAI) b
S, Ag, Agg
[2]
Overt Agitation Severity Scale (OASS)
S, Ag
[19]
Agitated Behavior in Dementia Scale (ABID)
S, Ag
[20]
Brief Agitation Rating Scale (BARS)
S, Ag
[21]
Aggressive Behavior Scale (ABS)
S, Agg
[26]
Rating Scale for Aggressive Behavior in the Elderly (RAGE)
S, Agg
[9]
Overt Aggression Scale (OAS) c
S, Agg
NPI-4-A/A Scale
S, Ag, Agg, I
[22]
Ryden Aggression Scale (RAS)
S, Agg
[23]
Irritability Questionnaire d
S, I
[27]
Irritability/Apathy Scale
S I
[28]
General Scale Assessing Aggression, Agitation, Hyperactivity, and Irritability
The NPI, [4] the most commonly used assessment tool in research on BPSD, screens for ten behavioral domains, including irritability/lability and agitation/aggression. Moreover, aberrant motor activity (Does the patient pace around the house without apparent purpose?), which may also be considered agitated behavior or hyperactivity, is assessed. Severity and frequency are assessed over the preceding month. Two additional versions have been developed, the NPI-Questionnaire (NPI-Q) [24], a shorter version of the original carried out as a questionnaire which only assesses severity, and the NPI-Clinician (NPI-C) rating scale [25], which expands on the original NPI. Importantly, the NPI-C assesses agitation and aggression separately, whereas the NPI and NPI-Q assesses these symptoms under one item. The NPI-Q is widely used and may be better suited for clinical use and has reasonable reliability across populations [29]. The BEHAVE-AD rating scale [3], which assesses several items, including aggression and activity disturbances, is interview based and rates behavior in the 2 weeks prior to assessment. Note that some scales assess behavior that may be considered as agitation (e.g., irrational or restless), aggressiveness (dangerous), irritability (annoying), or a mixture of these (e.g., verbal output disturbance and interpersonal difficulties), but these scales are not reviewed in this chapter. For a thorough review which includes these scales, see [30].
Specific Scales Assessing Aggression, Agitation, Hyperactivity, or Irritability
Aggression
Developed for use in nursing home populations, the Aggressive Behavior Scale [26] and the Rating Scale for Aggressive Behavior in the Elderly (RAGE) [9] can be administered relatively quickly (estimated at less than 5 min), but they only rate the frequency of the aggressive behavior, although RAGE contains items on the consequences of an action (e.g., hurting self and hurting others). The Overt Aggression Scale [31] and the Modified Overt Aggression Scale (MOAS) [32] rely on direct observations and require the rating of each episode of aggressive behavior.
Agitation
With several versions published, the CMAI [2] is probably the most widely used scale in research and is based on an interview with a proxy (e.g., carer or nursing home staff). The CMAI takes about 20–30 min to administer and assesses aggressive behavior, e.g., hitting, kicking, and verbal aggression. The Overt Agitation Severity Scale [19] was designed to explicitly rate agitation and exclude aggressive behavior. As with CMAI, only frequency and not intensity is assessed.
Irritability
Craig et al. developed the self-administered Irritability Questionnaire, but recognized its unsuitability for patients with cognitive impairment. Consequently a shorter version was created. This version, called the Carer’s Irritability Questionnaire [27], is administered to carers and rates both the frequency and intensity of irritability. The Irritability-Apathy Scale rates irritability and apathy and has been developed for use in AD and Huntington’s disease [28].
Hyperactivity
No scales exist specifically assessing hyperactivity. Hyperactivity is most often identified as a subsyndrome of agitation, irritability, euphoria, disinhibition, and/or aberrant motor behavior [5]. Therefore, a general scale assessing two or more of these items may be used to assess hyperactivity. For example, the NPI includes aberrant motor behavior, irritability/lability, euphoria, and agitation/aggression and may be used to assess hyperactivity.
Research on Agitation, Aggression, Irritability, and Hyperactivity
Epidemiology of Agitation, Aggression, Irritability, and Hyperactivity in Patients with Dementia
In general, BPSD are exceedingly frequent in patients with progression of dementia and most, if not all, patients will at some stage suffer from at least one BPSD [33].
Several large cohort studies and analyses of pooled data investigated the prevalence of agitation, aggression, irritability, and hyperactivity in outpatients with dementia. The prevalence of irritability on the NPI was 25–39 % and the prevalence of agitation was 28.6–44.3 % [6, 34, 35]. In a large-scale study comprising 2354 dementia outpatients [7], 31.1 % suffered from agitation and 32.1 % from irritability. Apathy was present in 55.2 % of the outpatients, making it the most common symptom, followed by anxiety (37 %) and depression (36.7 %). The authors of the study identified four subsyndromes, with hyperactivity (agitation, disinhibition, aberrant motor behavior, and irritability items on the NPI) as the second most prevalent symptom (63.6 %).
Regarding aggressive behavior, a prevalence of 76 % was found in a population of outpatients with AD. The CMAI was used to assess aggressive behavior. Factor analysis identified 4 subsyndromes, of which one was physically aggressive behavior occurring in 28.6 % of patients [36]. In another study using MOAS, the prevalence of aggressive behavior was 20.9 % [37]. In a large meta-analysis examining the prevalence and course of BPSD, prevalence rates for aggression ran from 6 to 26 %, hyperactivity had a similarly varying prevalence (34–65 %) as did wandering and agitation (18–62 %) [38]. Variance in prevalence rates may be explained by the use of different scales in the included studies as highlighted by the authors of the meta-analysis. The authors further point toward difference in time intervals between assessments and differences in length of follow-up as sources of variance.
Prevalence and Longitudinal Trajectory According to Setting and Disease Stage
Two meta-analyses investigated the prevalence of BPSD in nursing home residents with dementia [39] and community-dwelling patients with dementia [38]. The prevalence of agitation, aggression, hyperactivity, and irritability varied greatly between studies both in nursing home residents and in community-dwelling patients. Although no formal comparisons were carried out between the two patient groups, there are no clear differences in the prevalence of agitation, aggression, irritability, and hyperactivity between the populations. Synthesis of data was not possible due to heterogeneity of the populations and the use of different scales, but prevalence in most studies of community-dwelling patients in the meta-analyses indicated an increase in prevalence in hyperactivity, agitation, and aggression during follow-up. The studies did not report a similar trend for nursing home residents.
Two large studies not included in the meta-analysis followed institutionalized patients for 53 months [40] and outpatients for 4 years [41]. Both studies applied the NPI for assessment of BPSD. In institutionalized patients, prevalence at first assessment was 29.2 % for irritability and 26 % for agitation in institutionalized patients. Prevalence increased in institutionalized patients in the three first assessments (third assessment at a mean of 935 days to 33 % for agitation and 36.5 % for irritability; no formal statistical tests were carried out) but decreased slightly in the fourth assessment (at a mean of 1580 days), though the severity of agitation increased [40]. Conversely, at first assessment in outpatients, a prevalence of 18 % for irritability and 18 % for agitation was found. In this study, the authors also investigated the prevalence of the subsyndrome of hyperactivity. This consisted of the items irritability, euphoria, aberrant motor behavior, disinhibition, and agitation on the NPI. The prevalence of hyperactivity was 34 %. Irritability was stable and agitation increased from 18 to 29.1 %, as did hyperactivity from 33.8 to 53 % [41].
Cheng et al. directly compared outpatients with AD and individuals with AD in institutions. Aggression was present in 36.2 % of outpatients and in 26.6 % of institutionalized patients. Activity disturbances (wandering, purposeless activity, inappropriate activity) were present in 52.2 % of outpatients and in 38.7 % of institutionalized patients. The severity of symptoms was comparable between the two groups [42].
Several studies investigated the effect of dementia severity on aggression, agitation, irritability, and hyperactivity as well as other BPSD. In 3768 patients with dementia [43], the prevalence of agitation/aggression increased with dementia severity as measured by the Clinical Dementia Rating scale. Mild dementia was associated with a 35 % prevalence of agitation/aggression, moderate dementia with 47 %, and severe dementia with 56 % across dementia subtypes. For irritability, a less clear pattern emerged, with an increase in prevalence from mild to moderate dementia and a decrease from moderate to severe. A similar pattern was found for apathy, whereas prevalences decreased for depression/dysphoria. Using MMSE to stage dementia severity (i.e., by the level of cognitive function) in nursing home residents, a very clear association between dementia severity and aggression and agitation was found. Physical aggression was reported in 8 % of patients with mild dementia (defined as MMSE between 19 and 24) vs. 40.6 % for severe (defined as MMSE between 0 and 9), nonphysical aggression in 42 % vs. 67.2 %, and verbal agitation in 64 % vs. 80.6 % [44]. Van der Mussele compared agitated and non-agitated patients, and although agitated patients showed more frequent presence of all symptoms, this difference was most pronounced for disinhibition (19.8 % vs. 52.5 %), euphoria (27.1 % vs. 49.5 %), restlessness (9.4 % vs. 65.7 %), activity disturbance (12.5 % vs. 66.7 %), and aggressiveness (15.6 % vs. 73.7 %) [36]. In a study including outpatients with AD, change in both cognition and dependence over a follow-up period of 6 years was correlated with change in aggression/agitation, whereas depressive symptoms and psychosis were not. Importantly, the association with dependence was independent of decline in cognition [45].
In conclusion, agitation, aggression, irritability, and hyperactivity become more frequent over time in patients with dementia and more prevalent as the disease progresses. This is in contrast to other BPSD, such as anxiety and depression. However, comparisons between studies are difficult due to methodological issues, such as the use of different scales for assessment of symptoms, populations included in the studies, study setting, and dementia severity. Furthermore, it is important to keep in mind that although most BPSD fluctuate, this is especially true for aggression, which tends to occur periodically. Similarly, conclusions regarding differences in prevalence in outpatient versus institutionalized patients should be drawn with care. One intriguing observation, however, is that several studies reported lower prevalence of aggression/agitation in institutionalized patients even though BPSD are a common cause of institutionalization, indicating that institutionalization, or factors related to institutionalization, such as better access to professional care and care facilities designed to accommodate patients with dementia, possibly benefits BPSD. Future studies should pursue this issue further.
Prevalence and Longitudinal Trajectory According to Diagnosis and Cognitive Profile
BPSD patterns vary across neurodegenerative dementia disorders. For example, depression and agitation are common in AD, as is depression and apathy in vascular dementia. In behavioral variant frontotemporal dementia (bvFTD), apathy, disinhibition, changes in eating behavior, and impaired judgment are common. Hallucinations and delusions are common in DLB. Both aggression and agitation are common across dementia subtypes, but reports are conflicting regarding differences. In a study including 3338 patients with AD, 241 with DLB, and 189 with bvFTD, patients with AD displayed aggressive/agitated behavior and irritability least often, with DLB more often and with bvFTD most often [43]. Several other studies are in line with these findings [46, 47], whereas others reported conflicting results for aggressive/agitated behavior as being as prevalent, or more, in AD compared to DLB or bvFTD [48–50]. Aalten et al. (2008) examined the stability of subsyndromes across dementia diagnoses (AD, bvFTD, DLB, others) and found no effect, including on hyperactivity. However, there was an effect of dementia severity [51], the inconsistency of the findings perhaps due to differing dementia severities between diagnostic groups. Another possible explanation is a bias toward a diagnosis of bvFTD when certain symptoms (such as agitation and disinhibition) are present, leading to an overestimation of these symptoms in this patient group.
Causes of Agitation, Aggression, Irritability, and Hyperactivity
BPSD are likely a result of biological factors, neurodegenerative disease processes, acute medical illness, social circumstances, psychotic symptoms, sleep disturbances, psychological mechanisms, and traits of the patients as well as carers, but also a result of external demands the patient may have difficulties meeting due to insufficient internal resources. In other words, the development of BPSD is multifactorial. Nevertheless, when BPSD are encountered, especially agitation, aggression, irritability, and hyperactivity, emphasis should be put on diagnosing acute somatic or psychiatric illness, since they are a common cause and, in many instances, are easily treated. Infections, pain, and urinary retention are examples of the many possible causes of BPSD and will be reviewed in Sect. 9.4 “Management of Agitation, Aggression, Irritability, and Hyperactivity” of this chapter and in Sect. 9.3.3 “Biological Mechanisms in the Development of Agitation, Aggression, Irritability, and Hyperactivity.”
Biological Mechanisms in the Development of Agitation, Aggression, Irritability, and Hyperactivity
Imaging Findings
Imaging studies using MRI and other modalities have indicated that agitation and aggression are associated with focal brain atrophy as opposed to diffuse atrophy. Several different regions have been identified, including frontal, temporal and insular areas, and the cingulate gyrus.
Trzepacz et al. (2013) studied 462 patients with AD and mild cognitive impairment (MCI) using magnetic resonance imaging (MRI) and found that the left hippocampus, right superior frontal cortex, right amygdala, and bilateral insula were associated with aggression and agitation in AD patients, independent of demographics, apolipoprotein E (ApoE) status, and MMSE score [52]. Similar, but not completely overlapping, regions were identified in the same study for MCI patients and especially frontal atrophy was found to correlate with agitation and aggression across diagnostic groups. Not surprisingly, MCI patients who converted to AD within a 2-year follow-up showed greater overlap in brain regions associated with agitation and aggression than non-converters. This indicates early involvement of these brain regions in agitation and aggression. Findings of hypoperfusion in the dorsofrontal cortex in patients displaying aggressive behavior further support frontal lobe involvement [53], although another study did not find this association [54]. Both studies, however, did find temporal cortical hypoperfusion.
Results are also conflicting regarding the involvement of the insula in agitation. Bruen et al. (2008) found that agitation was associated with decreased volume in the left insula and in the anterior cingulate cortex bilaterally [55], whereas another study did not find any association [56].
Neurotransmitters
The serotonergic, dopaminergic, and norepinephrinergic neurotransmitter systems have been studied in relation to agitation, aggression, irritability, and hyperactivity.
Investigations of the concentration of serotonin and dopamine metabolites in cerebrospinal fluid (CSF), as well as dopamine and norepinephrine activity, established that higher dopamine activity was associated with aggression and agitation in bvFTD. Moreover, serotonergic modulation of dopamine activity was correlated with aggression, indicating that the interaction between these two neurotransmitter systems plays a role in aggression. This finding was demonstrated in DLB but not AD patients, and the mechanism behind this difference remains undetermined [59]. Another study examining the same metabolites and neurotransmitters failed to find similar associations [60]. Several studies investigated genetic aspects of the dopamine and serotonin neurotransmitter systems in relation to BPSD. One study reported an association with a polymorphism in the dopamine transporter and agitation [61], but others did not found an association with polymorphisms in the dopamine receptors and aggression, agitation, irritability, and hyperactivity [62–64].
Cerebrospinal Fluid
Bloniecki et al. (2014) examined core AD biomarkers in CSF and found an association between agitation and total and phosphorylated tau in AD patients [65], which is in line with a postmortem study [66] in which forebrain tangle concentration was associated with agitation. Interestingly, no significant difference in prevalence of agitation was found in bvFTD patients divided by whether tau pathology was present at the postmortem neuropathological examination or not [67]. Tau pathology has also been associated with aggressive behavior. Specifically, neurofibrillary tangle load in the hippocampus was found to be associated with aggression in patients with unspecified dementia. Lastly, anti-inflammatory interleukins were found to be inversely associated with agitation [68].
Genetics
Several studies examined the effects of the ApoE risk allele on BPSD. In a large study comprising 1120 patients with AD [69], no association was shown with aggression, agitation, or irritability, whereas one small study reported an association with the ApoE 4 allele and agitation/aggression [70]. Interestingly, one study also reported that the ApoE 4 allele also conferred a higher risk of aggression in bvFTD [71], although the ApoE 4 allele does not confer a higher risk of bvFTD [72].
Conclusion
Research on the underpinning biological mechanisms and disease processes leading to aggression, agitation, irritability, and hyperactivity is hampered by methodological issues such as small samples and different definitions of behavior. It is reasonable to assume that focal neurodegeneration leading to atrophy and hypometabolism is involved in the underlying mechanisms. Imaging findings most consistently show the involvement of frontal regions. Other areas of interest are temporal regions, insula, and the cingulate gyrus. Findings of an association between aggression and agitation and tau in CSF and in neuropathological examinations further strengthen the assumption that neurodegeneration plays a role in the evolution of BPSD. Changes in neurotransmitter systems may also play a role in the development of symptoms, but the results reviewed are conflicting. Further studies should pursue investigations using PET imaging with relevant ligands. Finally, biomarkers which may help in the diagnosis and prognostication of agitation, aggression, irritability, and hyperactivity are as yet unidentified, indicating that further studies are needed.
Impact of Agitation, Aggression, Irritability, and Hyperactivity
Many clinicians may not be attentive to the fact that agitation, aggression, irritability, and hyperactivity are associated with a high degree of distress in patients and in formal and informal carers, surpassing even more defining symptoms of dementia such as memory problems. An analysis of data from a sample of 177 dementia carers supports this finding. Memory problems were the most frequent but least distressing symptom, whereas disruptive behavior was the least frequent but most distressing symptom. Irritability and agitation were equally distressing and significantly associated with the number of depressive symptoms in carers [73]. Several studies found an association between burden on formal and informal carers and BPSD, including agitation and aggression, across dementia severity and dementia types [74–77]. Moreover, agitation, aggression, and irritability are found to be very burdensome, also compared to other BPSD [78, 79]. Caring for a person with dementia is also associated with poor health and related outcomes, for example, self-reported poor health, reduced ability for self-care, higher mortality, higher stress levels, and poor sleep. Some of these outcomes are associated specifically with BPSD [80], but data are lacking with regard to agitation, aggression, irritability, and hyperactivity, although a relationship presumably exists.
BPSD also greatly impact the person with dementia and are associated with a decreased quality of life for both patients with dementia [81, 82] and carers [83]. Moreover, agitation/aggression can precipitate institutionalization and may also lead to a more rapid progression to severe dementia [84]. The presence of agitation/aggression may also require administering medications with the risk of unwanted side effects and increased mortality. Lastly, agitation/aggression is associated with higher cost of care, thus conferring a further burden on society [85].
Management of Agitation, Aggression, Irritability, and Hyperactivity
Correct diagnosis and management of agitation, aggression, irritability, and hyperactivity is important for rapid resolution of symptoms and to reduce associated morbidity. In the following, we describe a stepwise approach to diagnosing and managing agitation, aggression, irritability, and hyperactivity. This tailored approach emphasizes the need to identify specific causes for specific behavior in individual patients. The key issue is to first identify underlying causes in order to subsequently address these with non-pharmacological and/or pharmacological treatment as appropriate. The approach is a result of a synthesis of our own experience with agitation, aggression, irritability, and hyperactivity and approaches proposed by leading researchers in the field [86, 87]. The Describe, Investigate, Create, and Evaluate (DICE) approach was recently proposed following a process involving an extensive literature search and panel discussions with leading experts [86]. DICE outlines a four-step approach to diagnose and treat agitation and aggression. It incorporates a focus on identifying underlying causes and an emphasis on individualized efforts, suited to the patient. A comparable approach with regard to this clinical reasoning has been adopted in this chapter. Below in the section “Guidelines on Management of Agitation, Aggression, Irritability, and Hyperactivity,” guidelines addressing approaches similar to the present one may be found. Table 9.2 summarizes the approach proposed in this chapter for easy reference.
Table 9.2
Summary of general approach to the diagnosis and management of agitation, aggression, irritability, and hyperactivity
Step 1. Assess for underlying physical or psychiatric causes and consider |
Physical illness, e.g., infection, pain, sensory deficits |
Delirium or psychosis |
Review of patients’ medication |
Step 2. Address underlying specific causes identified in step 1, such as acute physical illness |
Step 3. Map behavior |
Type, frequency, when and where of behavior |
Step 4. Consider immediate pharmacological treatment of severe agitation and aggression (rarely indicated) |
Severe agitation and aggression that cause extreme distress for the patient or that put the patient or others at high risk may warrant immediate initiation of pharmacological treatment |
Step 5. First-line treatment: non-pharmacological |
Aimed at the patient, carers, and/or environment |
Careful observation; wait for possible spontaneous decrease of symptoms |
Step 6. Second-line treatment: pharmacological |
Consider anti-dementia medication, atypical antipsychotics, antidepressants, anticonvulsants/mood stabilizers, and, in rare instances, benzodiazepines |
When antipsychotic treatment is considered necessary, start low, go slow, monitor carefully, keep treatment period as short as possible, plan discontinuation/reconsidering the treatment, and be aware of black box warnings |
Step 7. Assess treatment effect |
Use appropriate scale for assessment of treatment (see Table 9.1) |
Step 8. Pay attention to carers |
Consider burden of symptoms on carers |
Paying attention to the physical and psychological health of carers is important |
Offer psychological counseling and respite care when needed |
General Approach to the Diagnosis and Management of Agitation, Aggression, Irritability, and Hyperactivity
Step 1
Assess for acute underlying illnesses, including acute or subacute exacerbations in chronic disorders. When encountering agitation and aggression, a thorough clinical assessment should be carried out to uncover medical illness, such as pain (e.g., injury, ill-fitting dentures, and other orthodontic problems), urinary tract infections, respiratory tract infections, problems with bladder emptying, cardiac disease, respiratory problems, obstipation, or anemia. These medical conditions are common in the elderly and may go undiagnosed and untreated in patients with dementia. Furthermore, they can easily be treated, often leading to resolution of the behavioral problems. It is also important to be vigilant regarding undiagnosed sensory deficits or unmet needs regarding, e.g., glasses or hearing aids. Agitation and aggression may also be signs of delirium, which is why the level of consciousness and alertness should be assessed. Underlying psychosis should also be considered and may require careful questioning of the patient or carers to uncover delusions or other psychotic symptoms. Lastly, substance or alcohol abuse, or abstinence, may play a role. We suggest a thorough clinical assessment, including measurement of temperature, test for urinary tract infection (also in the absence of high temperature and urinary symptoms), blood sampling (leucocytes, hemoglobin, glucose, C-reactive protein, electrolytes, and creatine), electrocardiogram (if cardiac disease is suspected), and an x-ray of the chest, if a chest infection is suspected. Moreover, the patient’s medication should be reviewed with emphasis on medications initiated or stopped immediately prior to onset of agitation, aggression, irritability, and hyperactivity. Medication with possible psychiatric or cognitive side effects should be examined extra closely. This includes drugs with anticholinergic, sedative, or other unwanted side effects (e.g., orthostatic hypotension).
Step 2
Treat the underlying specific causes identified in step 1, such as acute physical illness.
Step 3
Map behavior. If step 1 does not identify any acute underlying illnesses as the cause of the symptoms, further mapping of behavior should be carried out. This step is a continuation of step 1; hence the main focus should remain on identifying underlying causes. The presence of BPSD is usually brought to the attention of the clinician by dementia carers as opposed to direct observation by the clinician. Moreover, it is more often the carer as opposed to the patient who reports changes in behavior, although the behavior frequently affects the patient in negative ways. The clinician should determine which symptoms are present, how often, and when, as well as the severity and consequences of the behavior for the patient and their surroundings. It is important to ascertain whether severe aggression and agitation are present that may endanger the patient or people in the patient’s surroundings, since such symptoms may need immediate pharmacological treatment. In contrast, mild or moderate symptoms may permit a period of observation. Observation can be carried out by a carer keeping a diary of behavior, with as many episodes of unwanted behavior noted as possible. This includes a short description of the behavior, circumstances (e.g., in what situation, time of day, any preceding events), and duration. In cognitive-behavioral terms, this approach equates to the ABC approach (antecedents, behaviors, consequences). Some behaviors may be problematic for the carer but not the patient and vice versa. For example, aggressive behavior is burdensome for the carer, but may not be reported by the patient. Many BPSD, including agitation and aggression, resolve spontaneously over the course of 4–6 weeks. However, a period of observation should not be an invitation to have a nihilistic attitude toward the patient’s symptoms or a carer’s distress. A short period of observation, allowing symptoms to resolve spontaneously, will likely reduce the risk of initiating unnecessary therapy. We recommend using a validated scale to assess symptoms. When mapping has been carried out, a plan for the management of symptoms should be formulated. Patients and carers should be informed and involved in the plan, together with the physician, with emphasis on explaining the plan and the rationale to the patient and carer, also if a period of observation is warranted. Realistic and meaningful treatment targets should be formulated and communicated.
Other potentially modifiable and treatable causes of BPSD include psychiatric comorbidity, poor sleep, overstimulation, stressors in the physical environment (e.g., cluttered room, lighting, and noise), understimulation (boredom), breech of patient’s personal boundaries, and unmet needs. Factors associated with the carer should also be considered, such as communication style, approach to care, interpersonal relationship between carer and patient, over- or underestimation of the patient’s ability, unmet needs in the carer, stress and depression, and other medical or psychiatric comorbidities in the carer. Aggression is often a reaction to specific triggers in the environment, as exemplified by the common occurrence of aggression in relation to delivery of care. As a result, it is important not to “decontextualize” symptoms but rather to analyze them in the context in which they occur. This will often be helpful in identifying causes, which may otherwise be considered innocuous.
Step 4
Consider immediate pharmacological treatment of severe agitation and aggression (rarely indicated). In cases of severe agitation and aggression that cause extreme distress for the patient or that put the patient or others at high risk, acute pharmacological treatment may be initiated after exclusion of somatic causes. However, it is important to keep in mind that agitated and aggressive behavior often causes carers to solicit pharmacological treatment in the belief that it delivers rapid, effective relief. Pharmacological treatment will be reviewed below.
Step 5
First-line treatment: non-pharmacological. If no underlying medical illnesses have been identified, and if the symptoms require treatment, first-line treatment should be instituted. Non-pharmacological treatment may include specific measures tailored to a particular situation and aimed at individual causative factors, but also nonspecific interventions such as aromatherapy or physical exercise.
Step 6
Second-line treatment: pharmacological. Pharmacological treatment may be considered if non-pharmacological treatment fails to ameliorate symptoms.
Step 7
Assess treatment effect. It is important to have a plan for the reassessment of symptoms regardless of whether treatment or a period of observation is instituted. A validated scale for assessing BPSD should be used and we recommend using a general scale such as the NPI.
Step 8
Pay attention to carers. When dealing with BPSD, it is important to be attentive to informal carers’ stress and morbidity with regard to aggression, agitation, and psychosis. This should include social interventions such as providing relief to live-in carers (e.g., spouses), instituting formal care, encouraging self-care (e.g., seeking medical attention if needed), and being attentive toward their own depressive symptoms. Carers may benefit from contacting patient organizations, which can provide support, education, and peer support groups. Behavioral problems may be stigmatizing for the carer for cultural or social reasons, leading to social isolation and a delay in seeking help. Professionals need to address this by explaining the nature and possible reasons for the behavior, stressing that such symptoms are as much a part of the symptomatology of the disease as, e.g., cognitive symptoms.
Clinical Examples of Diagnosis and Management of Agitation, Aggression, Irritability, and Hyperactivity
Case 1
A 73-year-old man, diagnosed with Alzheimer’s disease 2 years ago, developed behavioral symptoms over the preceding 2 weeks.
At the last clinical assessment 3 months ago, MMSE score was 18. He was medicated with an acetylcholinesterase inhibitor, a cholesterol-lowering drug, and two types of antihypertensive drugs. The patient was living with his wife.
His wife had made an appointment with the neurologist due to increasing behavioral problems, which begun about 2 weeks ago. The patient had become less and less active. He did not want to go for walks as he usually liked to do, and he had become irritable when asked to carry out even small tasks. At night he would get irritable when the couple were getting ready to go to bed and seemed agitated. He took to pacing around the room, repeatedly sitting down and standing up again. Once or twice, he had raised his voice and yelled at his wife.
On examination the patient was awake but not able to identify date or where he was. MMSE was 19. The NPI was administered to the patient’s wife and a total score of 19 was reached (agitation/aggression = 9; irritability/lability = 9; aberrant motor behavior = 1). The neurological examination was otherwise unremarkable. On auscultation of the lungs, fine crackles were heard over both lungs. The patient was dyspneic when moving around in the room. Pulse oximetry revealed an oxygen saturation of 94 %. The patient had slight crural edema.
The neurologist suspected cardiac incompensation and ordered blood samples, ECG, and chest x-ray, and the patient was admitted to the cardiology ward.
Further examination revealed that the patient had suffered a small myocardic infarction with reduced ejection fraction and subsequent cardiac incompensation. After appropriate treatment including diuretics, the patient’s breathing became less labored. At discharge, the patient was not agitated. At a follow-up visit a few weeks later, the wife reported that the patients no longer seemed agitated or irritable. NPI was 2.
The patient’s symptoms of irritability and agitation were most likely triggered by the labored breathing which made walking and physical activity arduous. When supine, pulmonary edema tends to worsen, which most likely elicited the agitation at bedtime, mimicking a circadian rhythm. Patients with dementia may have difficulty reporting physical unease, due to speech difficulties, memory loss, or impaired insight and judgment.
Case 2
An 80-year-old woman was diagnosed with vascular dementia 4 years ago. She moved to a nursing home approximately 6 months ago following progressively worsening cognitive function, which made independent living impossible. The move was without difficulty. The patient had an episode of psychotic symptoms in the form of delusions and hallucinations 2 years ago due to a urinary tract infection.
The nursing home staff became increasingly concerned with the behavior of the patient over a period of 1 ½ months due to episodes of agitation. Specifically, episodes occurred in the evening in the form of shouting and occasional obscene words. Moreover, the patient would sometimes get up and pace around the common room in an agitated state without the carers being able to calm the patient. Furthermore, there was an instance where the patient tried to push a fellow nursing home resident. The care staff did not noticed any signs of psychotic symptoms.
On examination the patient was awake and lucid. MMSE was 15. NPI was 16 (aggression/agitation = 9; irritability/lability = 4; disinhibition = 2; aberrant motor behavior = 1). There were no signs of infection (including urinary tract infection) or other physical illnesses. Routine blood samples were unremarkable. There were no signs of depression, and sleep was unremarkable. The doctor was unable to find any obvious causes of the change in behavior. The symptoms were relatively moderate as indicated by the NPI. Therefore, a period of observation was agreed upon to map out any patterns or triggers in the environment. At a follow-up appointment 4 weeks later, care staff reported that episodes of agitation seemed to cluster around evening meals. Evening meals are eaten in the common room. Moreover, other activities that were conducted in the living area at the common table, where evening meals were served, seemed also trigger the unwanted behavior. The staff noticed that the episodes were elicited if the patient was seated across from a fellow male nursing home resident. When questioned, the patients confirmed that she was scared of the male resident. He reminded her of her father with whom she had a strained relationship.
After the staff became aware of this, the patient was never seated across the male resident so that she could not see him. Instead she was seated on the same side of the table as the male resident. No new episodes of agitation had occurred since then.
A period of observation may help to reveal causes of agitation, aggression, irritability, and hyperactivity. In many instances, there is no need for immediate treatment, allowing for such a period to be carried out.
Guidelines on Management of Agitation, Aggression, Irritability, and Hyperactivity
Several guidelines which include recommendations regarding diagnosis and management of BPSD are available, for example, from the National Institute for Health and Care Excellence (NICE) in Great Britain [88], the American Psychiatric Association [89], and European Federation of Neurological Societies [90]. Azermai et al. conducted a systematic appraisal of dementia guidelines for the management of behavioral and psychological symptoms and identified 15 guidelines eligible for inclusion, and after defining further criteria, five were deemed to be of a high enough quality (based on the AGREE rating system) for the final review [91]. The guidelines came from the Dutch College of Clinical Geriatrics (2005) [92], NICE (2006) [88], the Scottish Intercollegiate Guidelines Network (2006) [93], the Third Canadian Consensus Conference (2007) [94], and the Malaysian Ministry of Health (2009) [95]. All of the guidelines dealt with BPSD in general, although specific symptoms such as agitation and aggression were addressed individually in instances where evidence or clinical practice dictated such considerations. Across guidelines, and for BPSD in general (i.e., not only for agitation, aggression, irritability, and hyperactivity), there was consensus that first-line treatment was non-pharmacological and that second-line treatment was pharmacological. The following specific non-pharmacological treatment approaches were addressed in the guidelines: aromatherapy (addressed by four guidelines [88, 93–95]), multisensory stimulation (addressed by four guidelines [88, 93–95]), music therapy (addressed by four guidelines [88, 93–95]), massage (addressed by three guidelines [88, 93, 94]), and bright light therapy (addressed by three guidelines [93–95]). None of the interventions were recommended specifically for agitation, aggression, irritability, or hyperactivity in the guidelines.
Regarding agitation/aggression and pharmacological therapy in particular, four guidelines recommended haloperidol, olanzapine, and risperidone [92–95]. All guidelines highlighted potential side effects, some severe, as a limiting aspect to the use of antipsychotics. The guidelines also agreed that the use of antipsychotics should be time limited and two guidelines addressed planned discontinuation, recommending structured discontinuation after a period of stability [94, 95]. Moreover, for agitation in the context of anxiety, all guidelines recommended short-term benzodiazepine treatment. No guidelines recommended antidepressants, except in the case of depression, were all guidelines recommended its use. All guidelines addressed acetylcholinesterase inhibitors (AChEIs) for BPSD in AD and memantine by four guidelines [88, 93–95], although not specifically in relation to agitation, aggression, irritability, or hyperactivity. The included guidelines were all published from 2005 to 2007. Many of their principles are still recommended but others may be considered less relevant, which must be taken into account. Specifically, more recent studies have now clearly demonstrated severe side effects associated with antipsychotic treatment. We will review evidence with regard to this aspect in later Sect. 9.4.6 “Pharmacological Treatment: Evidence.”
Non-pharmacological Treatment
Non-pharmacological strategies encompass a large variety of highly heterogeneous approaches. Many guidelines and various experts recommend non-pharmacological treatments as first-line treatment, but fail to recommend specific options [80–90, 93–95]. Synthesizing data in the form of, for example, meta-analyses is difficult since intervention methodologies vary, outcome measures differ, and the populations and settings are not comparable, or there is a lack of methodological rigor that limits evaluation of the efficacy of treatment [86, 87]. Moreover, evaluating the efficacy of non-pharmacological treatment on specific behaviors such as aggression, agitation, irritability, and hyperactivity is also hampered further by the fact that most studies examine the effects on BPSD in general. In this context, it is pertinent to highlight that lack of evidence does not equate to lack of efficacy.
In addition, the clinician may meet obstacles to implementing non-pharmacological approaches, which will need to be addressed in the first place. For example, carers may prefer drugs to non-pharmacological approaches due to their perception of the effectiveness of the latter and the fear that the patient they are caring for may become violent. Other obstacles include staff insufficiently trained in the use of non-pharmacological strategies and the time-consuming nature of the strategies.
As stated non-pharmacological strategies are heterogeneous and no consensus exists on the classification of treatments, in contrast to pharmacological treatments, which are often classified based on the mechanisms of action. Kales et al. (2015) [86] suggested dividing treatments into three categories: interventions aimed at the patient with dementia, interventions aimed at the carers, and interventions aimed at the environment. Livingston et al. (2014) [96] conducted a systematic review of non-pharmacological interventions with regard to their efficacy in treating agitation in patients with dementia. Here, interventions were divided into interventions working with the person with dementia, sensory interventions, working through care home staff, exercise, and training caregivers without supervision.
Interventions Aimed at the Patient with Dementia
This category comprises many different types of interventions [88, 97–117] and is not easily compared. Many have shown some efficacy on BPSD, but only a few have shown efficacy specifically regarding agitation or aggression.
A few randomized controlled trials (RCTs) indicate that music therapy may be effective for agitation and aggression [98, 106–109, 118–120]. A meta-analysis of three of these studies indicated a significant and immediate effect on agitation in nursing home residents. However, there was no evidence for a long-term effect and for patients with severe agitation [96]. Studies also show that strategies such as distraction, backing away, and leaving the room are helpful for symptoms of aggression [121]. Two RCTs provide evidence that hand massage reduces agitation in the short term [114]. Studies in nursing home residents suggested that personalizing the bathing experience (e.g., offering choices and creating a spa-like atmosphere) can reduce agitation and aggression during bathing [122]. The evidence for all these therapies, however, is scarce and better quality studies are needed. Many guidelines suggest that some type of psychological intervention should be the first approach to agitation or aggression [91]. This includes validation therapy, for which some evidence exists to suggest efficacy [97]. Another approach includes a tool box comprising simple and practical psychological interventions, such as structured social interaction and meaningful activities, which can be individualized. This was tested in a single non-RCT [87].
Related posts:
Depression and Anxiety in Dementia Subjects
Psychosis in Dementia
Toward a Family-Sensitive Practice in Dementia
Behavior Symptoms in Primary Progressive Aphasia Variants
Inappropriate Sexual Behaviors in Dementia
Family Issues in Behavioral and Psychological Symptoms of Dementia: Unraveling Circular Pathways?
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
