Agitation in Alzheimer’s disease: From assessment to therapeutics

Abstract

Agitation is a neuropsychiatric syndrome characterized by excessive motor and/or verbal behaviors, with or without aggressive behaviors. The prevalence of agitation in Alzheimer’s disease varies from 5% to over 50%. Multiple factors have been implicated in its pathophysiology, including disease stage, comorbidity with other symptoms (e.g., psychosis, anxiety/depression), and psychosocial factors. Ruling out delirium and identifying environmental triggers are fundamental steps in the management of agitation in Alzheimer’s disease. For establishing an effective therapeutic plan, it is important to define duration, severity, and potential for harm. While non-pharmacological approaches are considered the first line of intervention, pharmacological agents are frequently used in the treatment of agitation. Antipsychotics are commonly used in acute agitation. For chronic agitation, serotonin-selective reuptake inhibitors, especially citalopram and escitalopram, are often preferred due to safety concerns associated with the long-term use of antipsychotics. Promising novel strategies, such as new compounds and neuromodulation, are likely to be incorporated into agitation therapeutics in the next few years.

Key Words: Alzheimer’s disease; Dementia; Agitation; Aggression; Antipsychotics; Antidepressants

Core Tip: In Alzheimer’s disease, agitation is a clinically relevant neuropsychiatric syndrome managed by non-pharmacological and pharmacological approaches. Ruling out delirium, identifying and addressing environmental triggers (e.g., change in caregiver) are fundamental therapeutic steps. Antipsychotics (e.g., brexpiprazole, risperidone) are commonly used in acute agitation, especially in the context of potential harm to self and others. For chronic agitation, serotonin-selective reuptake inhibitors (e.g., escitalopram) are preferred.

INTRODUCTION

Virtually all individuals with Alzheimer’s disease (AD) experience neuropsychiatric symptoms, also known as behavioral and psychological symptoms of dementia (BPSD)[1-3]. These symptoms can occur at any stage of the disease but tend to be more frequent and severe during the moderate to late stages. Neuropsychiatric symptoms are a significant source of distress for both patients and their families, affecting the course of the disease and leading to increased healthcare costs and service utilization[1,2]. Agitation, a syndrome characterized by excessive motor and/or verbal behaviors, with or without aggressive behaviors, is one of the most notable BPSD[4,5]. A recent real-world assessment of the impact of AD-related agitation reported that all-cause healthcare costs (driven mainly by inpatient costs) and death were higher in patients with agitation who also had shorter time to institutionalization and death compared to patients without agitation[6].

The prevalence of agitation in AD varies widely, from 5% to over 50%, depending on the disease stage (with higher rates in advanced stages), and clinical settings (more common in institutions than in the community)[7,8]. The neurobiology of agitation in AD is complex, involving dysfunction across multiple neural circuits and neurotransmitter systems[9,10]. Briefly, agitation is primarily driven by an imbalance between key prefrontal and subcortical regions, resulting in impaired emotional regulation, response inhibition, and behavioral control. Monoamine neurotransmitter systems play a critical role in modulating activity within these brain regions and are markedly impacted by AD pathological changes. As a result, targeting these neurotransmitter systems may offer promising strategies for managing agitation in individuals with AD (Figure 1)[9]. In addition to neurobiological factors, psychosocial and environmental factors contribute to a heterogeneous presentation of agitation in AD[11].

Figure 1 Neurobiological model of agitation depicting key brain regions and neurotransmitter systems. Prefrontal cortex hypoactivity contributes to decreased executive control, while amygdala hyperactivity and striatal dopaminergic dysfunction increase emotional drive, collectively leading to agitation. Pharmacological targets include D2 receptor antagonists (antipsychotics) for dopaminergic dysfunction, selective serotonin reuptake inhibitors to reduce emotional drive, and α1-adrenoceptor antagonists (e.g., prazosin) to enhance executive control. Based on the model of agitation in Alzheimer’s disease proposed by Cummings et al[9]. SSRIs: Selective serotonin reuptake inhibitors; AD: Alzheimer’s disease.

This manuscript aims to review current trends in the assessment and management of agitation in the context of AD and related dementias. For this narrative, we searched for human studies addressing agitation in AD written in English, Portuguese, or Spanish from 2015 through May 2025. We searched the PubMed database using the keywords “agitation”, “dementia”, and “Alzheimer’s disease”. Pivotal clinical trials, relevant meta-analyses, and guidelines were identified and discussed in the following sections.

FORMAL DEFINITION AND ASSESSMENT

Agitation is a multifaceted term that encompasses a variety of behaviors associated with increased motor activity and related distress. Due to its inherent complexity, the International Psychogeriatric Association (IPA) convened a group of experts to develop a clinical consensus and research definition of agitation in cognitive disorders, following the Diagnostic and Statistical Manual (DSM) format[12]. A provisional definition was released in 2015, and a final definition was published in 2024[12,13]. The clinical and research definitions of agitation in cognitive disorders, as outlined by the IPA 2024 consensus, are provided in Table 1.

Table 1 Clinical and research definition of agitation in cognitive disorders according to the International Psychogeriatric Association 2024 Consensus.

Criterion	Features
Criterion A	The patient meets criteria for cognitive impairment or dementia syndrome regardless of its etiology
Criterion B	The patient exhibits at least one type of behavior [(1) Excessive motor activity; (2) Verbal aggression; and (3) Physical aggression)] associated with observed or inferred evidence of emotional distress (e.g., irritability, anger). This behavior has been persistent or frequent for a minimum of two weeks or the behavior represents a marked change from the patient’s usual behavior
Criterion C	Behaviors are severe and associated with excess distress or produce excess disability, including at least one of the following significant impairments: (1) Interpersonal relationships; (2) Other aspects of social functioning; and (3) Ability to perform or participate in daily living activities
Criterion D	While comorbid conditions may be present, the agitation is not attributable solely to another psychiatric disorder, medical condition, including delirium, suboptimal care conditions, or the physiological effects of a substance

Adapted from Sano et al[13].

To be classified as “with agitation”, a patient must meet the following criteria: The presence of a cognitive disorder (or dementia) (criterion A) and at least one behavior for a minimum of two weeks indicating emotional distress (criterion B) and causing distress or disability (criterion C). The behaviors associated with agitation are categorized into three groups: (1) Excessive motor activity (e.g., pacing, restlessness, shadowing); (2) Verbal aggression (e.g., yelling, cursing); and (3) Physical aggression (e.g., grabbing, resisting, throwing objects) (Table 1)[12,13]. It is important to note that agitation does not necessarily lead to aggression. When present, aggression can manifest in various forms and levels of severity, ranging from minimal to very high risk of harm to oneself or others[14].

Within the IPA framework, agitation cannot be attributed to delirium secondary to unstable medical conditions, such as diabetes or heart and kidney failures, or the effect of substances (criterion D) (Table 1)[13]. However, agitation is a frequent manifestation of delirium related to undiagnosed urinary tract infections, electrolyte imbalances (e.g., hyponatremia), and other medical issues. Therefore, ruling out delirium is a crucial step in defining agitation related to cognitive disorders[15]. Furthermore, the clinical evaluation of agitation in AD and other cognitive disorders involves characterizing the episodes by identifying types of behavior, severity, frequency, and duration, as well as examining any associated aggression or other BPSD. It is also essential to consider potential precipitating, aggravating, or perpetuating factors[16]. In this context, modifications to the environment - such as changes in housing and caregivers – should not be overlooked. The modifiable and non-modifiable risk factors for agitation in cognitive disorders are described in Table 2.

Table 2 Modifiable and non-modifiable risk factors for agitation in cognitive disorders.

Modifiable	Non-modifiable
Acute environmental changes (e.g., changes in caregiver and daily routine with over- and/or under-stimulation)	Advanced dementia
Caregiver attitude and interaction	History of psychiatric disorders, including antisocial and borderline personality traits or disorders
Current psychiatric disorder (e.g., depression)	Impulsivity
Physical or somatic illness (e.g., pain, thirst, hunger)	Impaired insight
Prescribed or illicit drugs (e.g., antihistamines, anticholinergics, alcohol)	Sensory impairments

Regarding the clinical assessment of agitation, validated instruments such as the Neuropsychiatric Inventory (NPI), the Behavioral Pathology in AD Rating Scale[17], and the Cohen-Mansfield Agitation Inventory (CMAI) can be effectively used (Table 3)[18]. NPI and Behavioral Pathology in AD Rating Scale address multiple BPSD and provide an overview of various challenging behaviors exhibited by patients, including apathy and sleep disorders. On the other hand, the CMAI is a behavior-specific tool that offers a more detailed perspective on agitation-related behaviors. Each of these instruments has its own advantages and disadvantages, and clinicians should select one based on their primary goal. For instance, in busy clinical settings, the NPI Questionnaire serves as a practical tool for identifying agitation and other BPSD[19]. The NPI Questionnaire is a brief, self-administered version of the NPI that focuses on the severity of symptoms rather than their frequency.

Table 3 Clinical assessment tools for agitation in older adults with Alzheimer’s disease.

Assessment tool	Dimensions evaluated	Application stage	Strengths	Limitations
NPI	Multiple behavioral and psychological domains, including apathy, anxiety, agitation/aggression, dysphoria/depression, delusions, hallucinations, among others	Different stages of AD	Broad coverage of symptoms; flexibility: Multiple versions suitable for different applications; available for rapid screening (NPI-Q) in busy clinical settings	Limited assessment of different agitation-related behaviors; the original version (NPI) is time-consuming
BEHAVE-AD	Multiple behavioral and psychological domains, including paranoid/delusional ideation, hallucination, activity disturbances, aggressiveness, among others	Different stages of AD, but better suitable for later ones (domains selected to reflect behaviors likely to respond to medications)	Broad coverage of symptoms	Less detailed than agitation-specific tools; less practical in time-constrained settings
CMAI	Different physical and verbal, aggressive and non-aggressive behaviors	Advanced stages of AD (developed to assess behaviors of older adults living in nursing homes)	Comprehensive characterization of agitation-related behaviors	Narrower scope; does not cover other behavioral and psychological symptoms

NPI: Neuropsychiatric Inventory; NPI-Q: Neuropsychiatric Inventory Questionnaire; BEHAVE-AD: Behavioral pathology in Alzheimer’s disease Rating Scale; CMAI: Cohen-Mansfield Agitation Inventory; AD: Alzheimer’s disease.

As previously mentioned, agitation tends to increase in frequency as AD progresses. This suggests that it is, at least in part, a reflection of the neuropathological changes affecting the brain areas involved in behavior control[9]. However, unlike the continuous decline in cognitive function, the trajectory of agitation and other BPSD is less predictable. In other words, agitation does not always become more frequent or severe over time; some individuals with dementia may even show improvements in their behavior[8]. Moreover, various factors contribute to agitation, including environmental and behavioral influences. Agitation can manifest as a response to physical discomfort (such as pain) or emotional distress. In the latter case, it may be associated with other BPSD, like anxiety, dysphoria, anger/irritability, and psychosis[20,21]. Understanding the relationship between agitation and other BPSD can have therapeutic implications. For example, while antidepressants may be effective for agitation associated with anxiety and dysphoria, they are unlikely to help in cases involving overt psychosis.

NON-PHARMACOLOGICAL INTERVENTIONS

Non-pharmacological approaches are widely accepted as the first line of intervention for managing agitation[11,22,23]. These functional analysis-based non-pharmacological interventions are largely based on adaptations of the Antecedent-Behavior-Consequence algorithm (antecedent-behavior-consequence)[24]. Overall, they typically include a step that identifies the context and triggering factors, followed by the description of the agitation-related behaviors, and an evaluation of the consequences, such as caregiver response[24]. Examples of these systematic approaches include the describe, investigate, create, and evaluate and the describe and measure, analyze, treat, and evaluate approaches[24-26].

Within this framework, the first step or phase is to recognize and manage environmental factors that may have contributed to an episode of agitation. For example, stable patients with AD can develop agitation, such as pacing, when placed in an unfamiliar environment during a family trip. Additionally, a change in caregivers can also trigger agitation, sometimes resulting in aggressive behavior. It is also important to carefully rule out delirium and review the medications in use[15]. Patients may experience agitation when they start or increase the dose of over-the-counter medications, such as antihistamines for allergies and anticholinergics for motion sickness. In advanced cases of AD, it may be appropriate to deprescribe dementia-related medications, such as acetylcholinesterase inhibitors, which could have activating effects in some patients[27,28]. The second step involves defining core features of agitation - particularly its duration (acute vs chronic), severity, and potential for harm[22]. Once delirium has been ruled out, medications reviewed, and agitation mapped, behavioral interventions can be implemented.

A variety of behavioral techniques can be employed depending on the severity of the episode. Measures for acute agitation with the potential for harm are often derived from general psychiatric practice and include techniques such as de-escalation, redirection and, if necessary, restraint and/or contention[23]. If agitation remains difficult to manage and/or based on the harm potential, pharmacological treatments may then be considered. A flowchart outlining the management of agitation in AD is proposed in Figure 2. It is crucial to establish realistic treatment goals beforehand, considering the complex trade-off between therapeutic benefits vs potential side effects of pharmacological treatments, especially in cases of chronic agitation. Engaging family members and caregivers in this process is essential and should be emphasized.

Figure 2 Flowchart outlining the management of agitation in Alzheimer’s disease. Acute agitation requires ruling out delirium and addressing modifiable risk factors, followed by the consideration of atypical antipsychotics and/or benzodiazepines alongside non-pharmacological interventions. Chronic agitation also involves addressing modifiable factors, with treatment options including selective serotonin recapture inhibitors, atypical antipsychotics, and non-pharmacological approaches. PFC: Prefrontal cortex.

PHARMACOLOGICAL INTERVENTIONS

When selecting the most appropriate pharmacological intervention for a patient with dementia, several factors must be considered. These include the severity of agitation, the risk of harm, previous responses to treatments, potential drug interactions, physical comorbidities, and the individual’s own perspectives. In acute hospital settings, algorithm-based approaches have been recommended, with the initial pharmacological step typically involving the use of antipsychotics[29]. In Canada and the United Kingdom, risperidone is approved for dementia-related agitation and is regarded as the preferred antipsychotic in this context[29]. Its effectiveness is supported by independent clinical trials and meta-analyses[30]. If rescue medication is required to help control agitation, trazodone and lorazepam are often the preferred options[29].

In the United States, various antipsychotics have been used off-label to manage dementia-related agitation, including risperidone, olanzapine, and quetiapine[31]. Quetiapine is the most commonly prescribed off-label antipsychotic for patients with dementia[31], partly due to its comparatively lower risk of motor side effects. However, quetiapine appears to be less effective than other antipsychotics. In the Clinical Antipsychotic Trials of Intervention Effectiveness AD study - a double-blind, placebo-controlled trial involving 421 outpatients with AD who also exhibited psychosis, aggression, or agitation - the time to treatment discontinuation due to lack of efficacy was similar for quetiapine (9.1 weeks) and placebo (9.0 weeks). In contrast, this time was significantly longer for olanzapine (22.1 weeks) and risperidone (26.7 weeks)[32]. Although olanzapine and risperidone demonstrated greater efficacy, their benefits were counterbalanced by higher discontinuation rates due to adverse events[32]. It is worth emphasizing the risks associated with the use of antipsychotics in older adults with dementia, including motor symptoms, such as parkinsonism and tardive dyskinesia, cognitive decline, and increased incidence of falls, cardiovascular (e.g., stroke, angina) and infectious (e.g., urinary tract, pulmonary) events, leading to higher risk of death[20,21]. Considering these potentially serious side effects, it is pivotal to monitor cardiovascular risk factors, including related biomarkers (blood pressure levels, glycemia, lipid panel, C reactive protein), and QT interval[20].

If the patient experiences recurrent or persistent agitation, antidepressants, particularly serotonin-selective reuptake inhibitors (SSRIs), are often preferred due to safety concerns associated with the long-term use of antipsychotics. Evidence strongly supports the efficacy of the SSRI citalopram in treating dementia-related agitation compared to other antidepressants like fluoxetine, sertraline, mirtazapine, and trazodone[33]. In the Citalopram for Agitation in Alzheimer Disease Study, 186 patients with probable AD and agitation were randomized to receive a psychosocial intervention plus either citalopram (10-30 mg per day) or placebo for 9 weeks[34]. During the study, administration of cholinesterase inhibitors and memantine was allowed, but no other psychotropic medications were permitted, with the exception of lorazepam and trazodone as rescue strategies for managing agitation and sleep problems. Patients receiving citalopram demonstrated improvements in all primary outcome measures related to agitation and most secondary outcome measures. However, there was a slight worsening in cognition and some patients experienced prolonged QT intervals. Notably, individuals with moderate agitation and less cognitive impairment showed a better response to citalopram, highlighting the variability in treatment responses[35]. It is important to remember that citalopram may take up to two months to reach its full therapeutic effect and is not effective for the immediate treatment of agitation or psychosis. The observation of QT prolongation has raised concerns about its cardiovascular safety[36]. In clinical practice, it is essential to assess risk factors for QT prolongation, such as bradycardia and hypokalemia, along with other medications that may affect the QT interval. Caution should also be exercised for citalopram doses above 20 mg, and monitoring with electrocardiogram and electrolyte measurements is recommended[36]. The therapeutic effects and potential side-effects of citalopram also appear to apply to its S-stereoisomer escitalopram, which has a maximum recommended dose of 10 mg[36].

In May 2023, the United States Food and Drug Administration (FDA) approved brexpiprazole for treating agitation in AD. This marks the first pharmacological approach approved for addressing BPSD. Brexpiprazole is an atypical antipsychotic targeting dopamine and serotonin receptors. Brexpiprazole is a partial agonist at serotonin 5-hydroxytryptamine_1A and dopamine D₂ receptors and an antagonist at serotonin 5-hydroxytryptamine_2A receptor. Brexpiprazole was initially approved by the FDA for the treatment of schizophrenia and later as an adjunctive treatment for major depression[37,38]. Three phase 3 studies assessed brexpiprazole for the treatment of agitation in AD. The first two studies reported that participants receiving 2 mg/day improved agitation but those receiving lower doses showed no clinically meaningful separation from placebo[38]. In the randomized, placebo-controlled trial involving 345 patients with agitation related to dementia, conducted in both care facilities and the community, brexpiprazole 2 mg/day or 3 mg/day significantly decreased agitation, as assessed by the CMAI, over 12 weeks[39]. The incidence of adverse effects was low, under 5%, and the rate of treatment discontinuation due to these effects (approximately 5%) was comparable to that of the placebo group. A meta-analysis of the three brexpiprazole trials did not find excess mortality in the brexpiprazole groups compared to placebo[40]. While this approval represents a significant advance to the field, its impact on real world practice is yet to be determined. More specifically, given the increased mortality and cardiovascular events with antipsychotic use in older adults with dementia, longer exposures in less selected populations could unveil events or effects not observed in the controlled studies.

Many drugs with diverse pharmacological profiles have been or are currently being trialed for the treatment of agitation in AD (Supplementary Table 1). Here, we highlight studies involving dextromethorphan-based compounds (dextromethorphan + quinidine or dextromethorphan + bupropion) and dexmedetomidine for agitation in AD.

Dextromethorphan is primarily used as a cough suppressant but, since 2010, its combination with quinidine has been approved by the FDA for the treatment of pseudobulbar affect[41], and the dextromethorphan + bupropion formulation was approved in 2022 for the treatment of major depressive disorder[42,43]. Both quinidine and bupropion act as cytochrome 2D6 inhibitors, thereby increasing the bioavailability of dextromethorphan. Dextromethorphan has a complex pharmacological profile, acting on glutamatergic, cholinergic, and monoaminergic systems[43,44]. In a 10-week phase 2 randomized clinical trial involving patients with probable AD (NCT01584440), the combination of dextromethorphan and quinidine demonstrated clinically meaningful effectiveness for managing agitation and was generally well tolerated[45]. Following these encouraging results, the FDA granted fast-track designation to the deuterated compound, AVP-786, allowing it to advance directly to phase III trials aimed at treating agitation in AD. The deuteration of dextromethorphan and quinidine improved pharmacokinetics, enhancing safety without affecting activity in the central nervous system. However, the outcomes of the two completed phase III trials involving AVP786 were contradictory. The first trial, TRIAD-1 (NCT02442765), indicated significant benefits in one of the two doses tested among 410 participants, while the second trial, TRIAD-2 (NCT02442778), which included 522 participants, failed to replicate these effects. Differences in study design likely contributed to these varying results. TRIAD-1 employed a sequential parallel comparison design, which increased statistical power, whereas TRIAD-2 used a conventional parallel design. Additionally, while both trials utilized the CMAI, the phase II study relied on the NPI Agitation and Aggression subscale[46].

Dexmedetomidine is an α2-adrenoceptor agonist currently administered intravenously in surgical procedures and intensive care settings for its sedative effects. A sublingual formulation of this medication (BXCL501) has been approved for treating acute agitation in patients with schizophrenia and bipolar disorder and is currently being investigated for its effectiveness in managing agitation in dementia. Positive results from the phase 1/2 TRANQUILITY trial (NCT04251910), completed in 2022, indicated that this therapy was well tolerated and rapidly reduced agitation in patients with various forms of dementia[47]. In 2024, the company reported positive results from the phase 3 TRANQUILITY II trial (NCT05271552), in which BXCL501 significantly alleviated agitation episodes in individuals with mild to moderate AD. They also reported that BXCL501 was generally safe and well tolerated, with no serious side effects. A related trial, TRANQUILITY III (NCT05665088), which aimed to assess the treatment in patients with more advanced dementia, was terminated for business reasons that were unrelated to safety or efficacy.

Changes in the monoamine neurotransmitter systems are recognized as the key factors contributing to agitation in AD, but imbalances in other neurotransmitter systems, such as glutamate and γ-aminobutyric acid, may also contribute to the development of agitation symptoms[9]. In this regard, anticonvulsants with mood-stabilizing effects have also been used off-label to manage agitation related to dementia, particularly valproate and carbamazepine. However, clinical trials and meta-analyses have not confirmed their effectiveness[48,49]. Additionally, there are concerns regarding their tolerability and safety.

KNOWLEDGE GAPS AND FUTURE DIRECTIONS

Despite its clinical relevance, the field of AD-related agitation has remained relatively stagnant for decades. Recent years have seen a surge of interest in this area, leading to the development of consensus definitions and therapeutic guidelines[3,12,13]. As reviewed above, structured approaches and non-pharmacological interventions have become the first therapeutic line for AD-related agitation. For acute severe agitation, antipsychotics have been used off-label, while SSRIs are often preferred for chronic agitation. In parallel, different pharmacological strategies have been explored, culminating with the FDA-approval of brexpiprazole for AD-related agitation in 2023[39,47,50]. While there is enthusiasm surrounding these advancements, it is essential to acknowledge the work that still needs to be done to address numerous questions and provide necessary care for these individuals.

First, despite the limited evidence of efficacy and the potential for serious side-effects, there remains an overreliance on pharmacological compared to non-pharmacological approaches[1,20,31]. Therefore, it is very important to disseminate and implement evidence-based non-pharmacological strategies for AD-related agitation[51,52]. One problem is the considerable gap in access to resources, such as therapists and professional caregivers, that must be addressed in different health systems[51,52]. Regarding novel non-pharmacological approaches, the therapeutic potential of neuromodulation is promising and requires further exploration. Electroconvulsive therapy, for example, is a safe and effective treatment for patients with dementia and severe agitation that is unresponsive to other therapies[53], yet it is rarely used in clinical practice. Factors such as cost and stigma may significantly influence this scenario. Mapping the neural circuits underlying well-defined behaviors could advance other neuromodulation techniques, such as transcranial magnetic stimulation, transcranial direct current stimulation, among others[54-56].

There is a significant need for the development of safer and more effective pharmacological alternatives. Multiple clinical trials using different compounds are currently ongoing for the treatment of agitation in AD (Supplementary Table 1). These compounds target neurotransmitter pathways traditionally implicated in the pathophysiological basis of agitation but the investigation of new mechanisms may be vital for establishing better treatments[9,10]. To reduce conflicting findings with the same compound, methodological differences should be minimized by using similar study designs, assessment tools, inclusion/exclusion criteria, primary and secondary outcomes.

In addition to therapeutic options, using ecological and digital tools (e.g., actigraphy, heart rate variability) to assess and measure agitation in both controlled studies and clinical practice can provide a more comprehensive understanding of the emergence of the related behaviors[57]. This can assist in identifying potential triggers and mitigators, leading to the development of more effective management approaches. In addition, other biomarkers of agitation (e.g., blood-based) can help track the longitudinal course of agitation, as well as predict therapeutic response to interventions[58]. Although the available therapeutic studies have not used these agitation-related biomarkers, future studies should incorporate them to monitor and/or predict the longitudinal course of agitation, as well as response to pharmacological and/or non-pharmacological interventions.

Finally, a critical evaluation of the impact of anti-amyloid and other disease-modifying therapies on BPSD, including agitation, will be necessary as these therapies are progressively introduced into clinical practice[59]. While the availability of disease-specific strategies is a very important advance in the field, there is still limited information on their influence on the long-term course of AD and management practices. It is possible that anti-amyloid therapies only delay the manifestation of BPSD, including AD-related agitation. In the hypothetical scenario where they might also minimize the severity and/or frequency of these behaviors, understanding this effect and the interaction among different therapeutic modalities will be fundamental in the management of people with AD.

CONCLUSION

In sum, this article provides an updated perspective on the assessment and management of people with AD and agitation, highlighting the recent advances in definition and therapeutics as well as important knowledge gaps.