Background and Objectives

The most recent edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) categorizes individuals with acquired cognitive deficits as having major or mild neurocognitive disorders (NCD).¹ Subtypes of NCDs include major and mild NCD due to Alzheimer's disease, due to frontotemporal disorder, due to Lewy bodies, and vascular NCD. Historically, patients with these NCDs have been referred to as having dementia. Because dementia is the far more familiar term, we have used it rather than NCD throughout this report.

Up to 90 percent of those with dementia exhibit behavioral or psychological symptoms at some point, more often in advanced stages of the disease.² Symptoms tend to occur in clusters and can include depression, psychosis, aggression, agitation, anxiety, and wandering.^2-4 Behavioral and psychological symptoms cause considerable patient distress and are associated with accelerated functional and cognitive decline. Dementia-related symptoms challenge both formal and informal caregivers and are associated with increases in caregiver anger, resentment toward the patient, stress, and decreased psychological health.^5-7 Not surprisingly, dementia-related symptoms are the leading predictors of institutionalization.⁸ However, staff in nursing homes and assisted living facilities are also challenged by behavioral and psychological symptoms, which affect an estimated 80 percent of nursing home and assisted living facility residents with dementia.

Among dementia-related symptoms, agitation and aggression are especially distressing to patients, family caregivers, and nursing home and assisted living facility staff. Agitation and aggression are costly to manage and are associated with institutionalization among community-dwelling patients, social isolation, and other negative outcomes.⁸ The terms agitation and aggression are used to describe many types of behaviors and many adjectives are used to describe agitated and aggressive behaviors (e.g., disruptive, problem, difficult, and challenging). Agitation is defined as “excessive motor activity with a feeling of inner tension and characterized by a cluster of related symptoms including anxiety and irritability, motor restlessness and abnormal vocalization, often associated with behaviors such as pacing, wandering, aggression, shouting, and nighttime disturbance.”⁹ Aggression is commonly described to be a subtype of agitation¹⁰ consisting of overt harmful actions (physical or verbal) that are clearly not accidental.⁹

Ultimately, terms describing agitation and aggression in the literature are confusing and inconsistent.¹¹ Agitation and aggression are typically grouped together as part of a spectrum, although they have different manifestations and implications. Agitation affects primarily the person with dementia (although the behaviors may be disruptive for others in his/her environment). By contrast, aggression directly involves at least one other person (the target of the aggression) and can represent a real risk to that person. As a result, one might argue that although it makes sense to identify and treat the underlying cause of agitation whenever possible, some manifestations of agitation may not need intervention per se; they can simply be tolerated. By contrast, aggression needs to be dealt with because of the possible risk to others. We refer to these symptoms or behaviors as agitation/aggression.

Historically, drugs have been used to manage behavioral symptoms in patients with dementia, particularly for agitation/aggression. Pharmacotherapy for behavioral symptoms is based on a biological/genetic framework for the etiology of the condition. However, drug therapies generally, and antipsychotic medications specifically, have limited efficacy and increased risk for adverse effects, including mortality.^12-14 Drug treatments for dementia are also associated with reduced quality of life.¹⁵ Evidence of effective nonpharmacological approaches would strengthen the efforts to urge less use of inappropriate psychoactive drugs, but the absence of that evidence should not diminish such efforts in light of the harmful effects of these medications. By contrast, the nonpharmacological approaches have virtually no reports of adverse effects.

Clinical guidelines recommend nonpharmacologic interventions as the first choice for agitation/aggression in patients with dementia.^16-19 However, nonpharmacologic interventions are under-used in clinical practice. In part this is because clinicians lack knowledge regarding their efficacy and possible risks, but caregivers are also reluctant to forsake drugs until they are confident in managing agitation/aggression without them. To reduce inappropriate use of antipsychotics and other psychotropic drugs for behavioral symptoms in patients with dementia will require evidence for the effectiveness and harms of nonpharmacologic treatments. Clinicians and caregivers will also need education on the use of these approaches.

Nonpharmacologic interventions aim to (1) prevent agitation/aggression behaviors, (2) respond to episodes of agitation/aggression to reduce their severity and duration, and/or (3) reduce caregiver distress. Individuals with dementia may reside in nursing homes or assisted living facilities or in their own homes or with family members (community-dwelling).

Interventions delivered in nursing homes and assisted living facilities can be at the patient level, where a therapy is delivered directly to the patient, or care delivery level, involving the approach, staff, and/or environment used in care delivery. Examples of patient-level interventions used in residential settings include sensory-based approaches such as aroma, bright light, or touch, as well as activity-based approaches involving music, art, or horticulture.²⁰ Care-delivery level interventions include a variety of care-delivery models, staff/caregiver education and training, and environmental approaches.²¹ Examples include trainings to enhance staff knowledge and skills in managing behavioral symptoms among residents, care-delivery models such as patient-centered care or dementia care mapping, and enhancements to the environment aimed at reducing exposure to agitation/aggression triggers.

Interventions delivered to community-dwelling individuals with dementia can be at the patient or caregiver level. The caregiver is typically an informal family caregiver. Patient-level interventions would be similar to those in residential settings. However, patient-level interventions may also include activities, such as exercise classes, that are accessible to individuals in less advanced stages of dementia. Caregiver-level interventions to address agitation/aggression address the family caregiver approach to caregiving. These interventions provide education and skills training to enhance understanding of the disease process, specific symptoms, and how to best address agitation/aggression. Table 1 provides a description and examples of the types of interventions used in various settings.

Table 1

Types of interventions addressing agitation/aggression in dementia.

The expected effectiveness of interventions will vary with their nature and purpose. Interventions designed to respond to a behavior are different from those designed to prevent the occurrence or intensity of such behaviors. In the former case, a successful intervention ends an episode, but the duration of effect is likely to be short. By contrast, a more preventive approach aims to have a longer lasting effect, marked by fewer events over a period of time. Although we attempted to classify interventions on the basis of the intent (i.e., responsive or preventive), we found that many studies failed to make the distinction clear.

Measuring behavioral outcomes is a complex process for which a wide variety of instruments are available. These instruments (1) are based on different theoretical frameworks, (2) are designed to evaluate behaviors in different settings (e.g., in-home, hospital, or long-term care), (3) are administered by different individuals (e.g., caregiver, nurse, or patient), and (4) use different mechanisms to obtain responses (e.g., interviews with patients or direct observation). More than 45 instruments are used to evaluate behavioral symptoms in dementia, with no gold standard.²² The appropriate instrument depends on disease severity and context of care (e.g., setting, severity of disease, and whether the purpose is to identify any behavior or to identify specific behaviors). Instruments for evaluating behavioral symptoms fall into two broad categories: general and specific.²² Table 2 describes commonly used instruments.

Table 2

Instruments measuring intermediate, primary, and secondary outcomes.

Several instruments measure agitation/aggression specifically. These include the Agitated Behavior in Dementia Scale (ABID),²³ the Cohen-Mansfield Agitation Inventory (CMAI),²⁴ and the Pittsburgh Agitation Scale (PAS).²⁵ Also, some general behavioral symptom instruments include subscales specific to agitation/aggression.

General measures evaluate a host of behaviors across multiple domains (e.g., agitation, depression, and wandering). Most studies that report results from general behavioral symptom measures report overall summary scores. Examples of general behavioral measurement instruments include the Neuropsychiatric Inventory (NPI and its variants NPI-C, NPI-Q). The NPI is one of the most commonly used instruments to measure behavior. The Revised Memory and Behavior Problem Checklist and the CERAD Behavior Rating Scale for Dementia are other examples of instruments measuring general behavioral symptoms in individuals with dementia.

Our understanding and measurement of agitation/aggression in individuals with dementia has changed over time. Agitation/aggression are now more often considered distinct behaviors. For example, an early version of the NPI combined agitation/aggression into a single domain. In contrast, the Neuropsychiatric Inventory Clinician (NPI-C), a second-generation survey designed to incorporate input from clinicians, separates the behaviors into two distinct domains.⁴ The context in which agitation/aggression occur is considered paramount to determining appropriate interventions. Clinical algorithms have been developed to help identify the presence and causes of symptoms in order to effectively manage behaviors.^26-28 However, instruments often document the occurrence of behavioral symptoms without identifying their source or cause. Ideally, algorithms are used alongside specific instruments to provide appropriate context for the occurrence of behaviors.

Evidence synthesis on the efficacy and comparative effectiveness of nonpharmacologic interventions specifically for agitation/aggression in patients with dementia could reduce the frequency and severity of those behaviors and improve functioning, reduce distress, and reduce or delay residential long-term care. These interventions may also reduce the use of antipsychotic drugs. Results from this review will inform practice regarding the appropriate and effective management of agitation/aggression in individuals with dementia.

To address these gaps in the literature, we conducted a systematic review based on an analytical framework (Figure 1) to address the Key Questions (KQs):

Key Questions

Key Question 1a: What is the comparative effectiveness of nonpharmacologic interventions in preventing and responding to agitation/aggression among individuals with dementia who reside in nursing home and assisted living settings?

Key Question 1b: What are the comparative harms of nonpharmacologic interventions in preventing and responding to agitation/aggression among individuals with dementia who reside in nursing home and assisted living settings?

Key Question 2a: What is the comparative effectiveness of nonpharmacologic interventions in preventing and responding to agitation/aggression among community-dwelling individuals with dementia?

Key Question 2b: What are the comparative harms of nonpharmacologic interventions in preventing and responding to agitation/aggression among community-dwelling individuals with dementia?

Analytical Framework

Figure 1Analytic framework for nonpharmacologic interventions to manage agitation/aggression in dementia

KQ = Key Question

Populations, Interventions, Comparisons, Outcomes, Timing, and Setting (PICOTS)

The PICOTS (populations, interventions, comparisons, outcomes, timing, and setting) addressed in this review are described in Table 3.

Table 3

Populations, interventions, comparisons, outcomes, timing, and setting (PICOTS).